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[ "ABSTRACT A healthy intestinal microbiota is considered to be important for priming of the infants ' mucosal and systemic immunity . Breast-fed infants typically have an intestinal microbiota dominated by different Bifidobacterium species . It has been described that allergic infants have different levels of specific Bifidobacterium species than healthy infants . For the accurate quantification of Bifidobacterium adolescentis , Bifidobacterium angulatum , Bifidobacterium bifidum , Bifidobacterium breve , Bifidobacterium catenulatum , Bifidobacterium dentium , Bifidobacterium infantis , and Bifidobacterium longum in fecal sample s , duplex 5′ nuclease assays were developed . The assays , targeting rRNA gene intergenic spacer regions , were vali date d and compared with conventional PCR and fluorescent in situ hybridization methods . The 5′ nuclease assays were subsequently used to determine the relative amounts of different Bifidobacterium species in fecal sample s from infants receiving a st and ard formula or a st and ard formula supplemented with galacto- and fructo-oligosaccharides ( OSF ) . A breast-fed group was studied in parallel as a reference . The results showed a significant increase in the total amount of fecal bifidobacteria ( 54.8 % ± 9.8 % to 73.4 % ± 4.0 % ) in infants receiving the prebiotic formula ( OSF ) , with a diversity of Bifidobacterium species similar to breast-fed infants . The intestinal microbiota of infants who received a st and ard formula seems to resemble a more adult-like distribution of bifidobacteria and contains relatively more B. catenulatum and B. adolescentis ( 2.71 % ± 1.92 % and 8.11 % ± 4.12 % , respectively , versus 0.15 % ± 0.11 % and 1.38 % ± 0.98 % for the OSF group ) . In conclusion , the specific prebiotic infant formula used induces a fecal microbiota that closely resembles the microbiota of breast-fed infants also at the level of the different Bifidobacterium species", "Preterm infants have an impaired gut barrier function . We aim ed to determine the effects of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ( short-chain galacto-oligosaccharides (SCGOS)/long-chain fructo-oligosaccharides ( LCFOS ) ) and acidic oligosaccharides ( AOS ) on intestinal permeability of preterm infants as measured by the sugar absorption test in the first week of life . Furthermore , we determined host- and treatment-related factors associated with intestinal permeability . In a r and omised controlled trial , preterm infants with a gestational age received enteral supplementation of SCGOS/LCFOS/AOS or placebo ( maltodextrin ) between days 3 and 30 of life . Intestinal permeability , reflected by the urinary lactulose/mannitol ( L/M ) ratio after oral ingestion of lactulose and mannitol , was assessed at three time points : before the start of the study ( t = 0 ) , at day 4 ( t = 1 ) and at day 7 ( t = 2 ) of life . Data were analysed by generalised estimating equations . In total , 113 infants were included . Baseline patient and nutritional characteristics were not different between the SCGOS/LCFOS/AOS ( n 55 ) and the placebo groups ( n 58 ) . SCGOS/LCFOS/AOS had no effect on the L/M ratio between t = 0 and t = 2 . In both the groups , the L/M ratio decreased from t = 0 to t = 2 ( P . Low BW increased the L/M ratio ( P = 0·002 ) . Exclusive breast milk feeding and mixed breast milk/formula feeding during the first week of life decreased the L/M ratio ( P enteral supplementation of a prebiotic mixture does not enhance the postnatal decrease in intestinal permeability in preterm infants in the first week of life", "BACKGROUND Galactooligosaccharides ( GOS ) and long-chain fructooligosaccharides ( lcFOS ) proliferate bifidobacteria in infant gut microbiota . However , it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring . OBJECTIVES We aim ed to test how supplementation with GOS and lcFOS ( GOS/lcFOS ) in the last trimester of pregnancy affects maternal and neonatal gut microbiota . Variables of fetal immunity were assessed as a secondary outcome . DESIGN In a r and omized , double-blind , placebo-controlled pilot study , 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS ( at a ratio of 9:1 ) or maltodextrin ( placebo ) from week 25 of gestation until delivery . Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal ( days 5 , 20 , and approximately 182 ) stool sample s. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis . RESULTS The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group ( 21.0 % and 12.4 % , respectively ; P = 0.026 ) ; the proportion of lactobacilli did not differ between the groups . In neonates , bifidobacteria and lactobacilli percentages , diversity and similarity indexes , and fetal immune parameters did not differ significantly between the 2 groups . Mother-neonate similarity indexes of bifidobacteria decreased over time . CONCLUSIONS GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates . The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables", "BACKGROUND Nondigestible carbohydrates ( NDCHs ) are fermented in the colon , where they can selectively promote the growth of bifidobacteria . OBJECTIVE Our aim was to determine the bifidogenic potential of different NDCHs used in human diets . DESIGN Two hundred healthy volunteers participated in this double-blind study . During phase 1 ( screening ) , 64 volunteers were r and omly assigned to 8 groups of 8 subjects each ; for 7 d , they ingested 10 g/d of 1 of the 7 NDCHs tested or of the placebo . During phase 2 ( dose-response study ) , 136 volunteers were r and omly assigned to 4 groups of 32 subjects who received 2.5 , 5.0 , 7.5 , or 10 g/d , respectively ( 8 subjects/dose ) , of one of the NDCHs that were proven to be bifidogenic during phase 1 and a fifth group of 8 subjects ( control subjects ) who received the placebo . Stools were recovered before and after NDCH consumption . RESULTS In phase 1 , 4 NDCHs were found to be bifidogenic : short-chain fructooligosaccharides ( P=0.008 ) , soybean oligosaccharides ( P=0.006 ) , galactooligosaccharides ( P type III resistant starch ( P=0.02 ) ; lactulose , long-chain inulin , and isomaltooligosaccharides were not bifidogenic . In phase 2 , the effects of 7-d treatment on bifidobacteria concentrations were found to differ significantly among the 4 NDCHs ( P=0.009 for time x treatment interaction ) . However , no significant differences were found among doses , and there was no significant dose x time interaction . A low baseline bifidobacteria count was significantly associated with the bifidogenic response to treatment ( P bifidogenic properties among the substrates and underlined the importance of taking into account the baseline bifidobacteria counts when evaluating the effect of the treatment", "BACKGROUND Serious infectious morbidity is high in preterm infants . Enteral supplementation of prebiotics may reduce the incidence of serious infections , especially infections related to the gastrointestinal tract . OBJECTIVE The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ( (SC)GOS/(LC)FOS ) and acidic oligosaccharides ( AOS ) on serious infectious morbidity in preterm infants . DESIGN In a r and omized controlled trial , preterm infants ( gestational age received enteral supplementation of 80 % (SC)GOS/(LC)FOS and 20 % AOS ( 1.5 g . kg(-1 ) . d(-1 ) ) or placebo ( maltodextrin ) between days 3 and 30 of life . Serious infectious morbidity was defined as a culture positive for sepsis , meningitis , pyelonephritis , or pneumonia . The analysis was performed by intention-to-treat and per- protocol , defined as > or = 50 % supplementation dose during the study period . RESULTS In total , 113 preterm infants were included . Baseline and nutritional characteristics were not different between groups . In the intention-to-treat analysis , the incidence of > or = 1 serious infection , > or = 1 serious endogenous infection , or > or = 2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups . In the per- protocol analysis , there was a trend toward a lower incidence of > or = 1 serious endogenous infection and > or = 2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group ( P = 0.09 and P = 0.07 , respectively ) . CONCLUSIONS Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants . However , there was a trend toward a lower incidence of serious infectious morbidity , especially for infections with endogenous bacteria . This finding suggests a possible beneficial effect that should be evaluated in a larger study . This trial was registered at is rct n.org as IS RCT N16211826", "BACKGROUND Gut hormones play an important role in the adaptation of the immature neonatal gut , and their secretion may be modulated by prebiotics . Furthermore , prebiotics are well known for their hypolipidemic potentials . We tested the hypothesis that prebiotics could alter motilin and gastrin secretion and reduce lipids in healthy preterms . METHODS A total of 167 newborns were r and omized to either a prebiotics enriched formula containing dietary oligosaccharides ( short-chain galacto-oligo-saccharides/long-chain fructo-oligo-saccharides [ scGOS/lcFOS ] ) , at a concentration of 0.8 g/100 ml , or a common preterm formula . Day 1 and 16 basal motilin , gastrin concentrations , and lipids were evaluated together with growth parameters , gastric residue , bowel habits , and feeding tolerance . Adverse events including necrotizing enterocolitis ( NEC ) and septicemia were also recorded . RESULTS Mean motilin increase and day 16 mean values were greater for the intervention , compared with the control group ( P = .001 , P = .005 , respectively ) , while gastrin remained high in both groups . Mean cholesterol and low density lipoprotein ( LDL ) increase were significantly greater in the control , compared with the intervention ( P = .037 , and P = .001 ) group . Day 16 LDL levels were significantly higher in the control group . Mean weight was increased in the control group , while gastric residue was less and stool frequency was increased in the intervention group . NEC and septicemia were not statistically different between groups . CONCLUSION A prebiotics enriched formula result ed in significant surge of motilin relating to reduced gastric residue , compared with a common preterm formula . Mean cholesterol change was lower , while LDL was not increased in the prebiotics group , compared with the control group", "Background Human milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine . In this study , the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low-molecular-weight galactooligosaccharides and high-molecular-weight fructooligosaccharides was analyzed in 90 term infants . Methods Two test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides . In the control formula , maltodextrin was used as placebo . At study day 1 and study day 28 , the fecal species , colony forming units ( cfu ) and pH were measured and stool characteristics , growth , and side effects were recorded . Results At study day 1 , the median number of Bifidobacteria did not differ among the groups ( 0.4 g/dL group , mean [ interquartile range ] 8.5 [ 1.9 ] cfu/g ; 0.8 g/dL group , 7.7 [ 6.1 ] cfu/g ; and the placebo group , 8.8 [ 6.1 ] cfu/g ) ( figures in square brackets are interquartile range ) . At the end of the 28-day feeding period , the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas ( the 0.4 g/dL group , 9.3 [ 4.9 ] cfu/g ; the 0.8 g/dL group , 9.7 [ 0.8 ] cfu/g ) versus the placebo group ( 7.2 [ 4.9 ] cfu/g , P The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas ( versus placebo , P change in fecal pH ( P the stool frequency result ed in a significant difference between the placebo group and the group fed the 0.8 g/dL formula at day 28 ( P stool consistency ( 0.8 g/dL versus placebo , P incidence of side effects ( crying , regurgitation , vomiting ) or growth . Conclusions These data indicate that supplementation of a term infant 's formula with a mixture of galacto- and fructooligosaccharides has a dose-dependent stimulating effect on the growth of Bifidobacteria and Lactobacilli in the intestine and results in softer stool with increasing dosage of supplementation", "OBJECTIVES Our goals were to determine the mortality risk for infants weighing 501 to 1500 gm according to gestational age , birth weight , and gender and to document birth weight-related changes in mortality and morbidity over a 5-year time period . STUDY DESIGN In this observational study perinatal data were prospect ively collected by the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network from May 1991 through December 1992 and compared with the corresponding data from 1987 through 1990 . St and ard definitions were used to record sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death . RESULTS The 1991 and 1992 cohort included 4279 in-born infants . Among their mothers 10 % were antenatal corticosteroids . Multiple gestations accounted for 20 % of the births . Fifty percent of the infants were delivered by cesarean section . During 1991 and 1992 the overall survival for infants weighing 501 to 1500 gm at birth was 81 % , compared with 74 % in 1987 and 1988 . Survival at birth weight 501 to 750 gm was 44 % ; it was 81 % at 751 to 1000 gm , 92 % at 1001 to 1250 gm , and 95 % between 1251 and 1500 gm . Female infants had a significantly greater chance of surviving than male infants at similar birth weights and gestational ages . At any given gestational age , smaller infants were less likely to survive . Survival in all birth weight categories increased between 1987 and 1992 , without accompanying increases in medical morbidity . Major morbidity increased with decreasing birth weight and included late-onset septicemia 22 % , chronic lung disease ( oxygen dependence at 36 weeks ' corrected age ) 18 % , severe intraventricular hemorrhage ( grade s III and IV ) 11 % , and necrotizing enterocolitis 5 % . Twelve percent of all infants were treated with corticosteroids for chronic lung disease , including 36 % of infants who were oxygen dependent at age 28 days . The mean length of hospital stay was 69 days for survivors and 18 days for infants who died . CONCLUSIONS Mortality for infants between 501 and 1500 gm at birth has declined over the past 5 years . There are interactions between birth weight , gestational age , gender , and survival rate . This increase in survival was not accompanied by an increase in medical morbidity", "There is some evidence that early colonization of the intestine affects the composition of the intestinal microbiota after weaning . In the present study , the effect of prebiotics administered from the first day of life on fecal counts of bifidobacteria and lactobacilli were studied during and after the administration of the prebiotics . In this double-blind , r and omized , placebo-controlled , explorative study , 20 newborns of hepatitis C virus-infected mothers who decided not to breast feed due to their concerns regarding their plasma viral load were r and omly assigned to either a formula with 8 g/L of a specific prebiotic mixture ( short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides , ratio 9:1 ) or a formula containing the same amount of maltodextrin ( placebo ) . Clinical examination including anthropometric measurements , microbiological analysis of fecal sample s , and blood leukocyte population analysis were performed at birth and 3 , 6 , and 12 mo age . At the age of 12 mo , hepatitis B vaccine-specific IgG serum titers ( Hepatitis B virus surface antibodies ) were also measured . Prebiotic supplementation result ed in more fecal bifidobacteria ( P lactobacilli ( P = 0.0044 ) compared with the placebo group . These differences between the groups were maintained during the second half of the first year without any prebiotic supplementation . There was no influence of the different diets on anthropometric data or the measured immunological variables . The data from this small explorative study indicate that early colonization of the intestine might have long-lasting effects on the composition of the intestinal microbiota", "Background : The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant . Objective : To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants . Study design : To resemble the effect of human milk , an oligosaccharide mixture consisting of 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides was used to supplement a st and ard preterm formula at a concentration of 10 g/l . This supplemented formula was studied in 15 preterm infants , and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo . A group fed fortified mother 's milk was investigated as a reference group ( n = 12 ) . On four days during a 28 day feeding period ( 1 , 7 , 14 , and 28 ) , the faecal flora was investigated , and stool characteristics , growth , and possible side effects were recorded . Results : During the study period , the number of bifidobacteria in the group fed the oligosaccharide supplemented formula increased to the upper range of bifidobacteria counts in the reference group . The difference between the supplemented and non-supplemented groups was highly significant ( p = 0.0008 ) . The stool characteristics were also influenced by the supplement : the stool frequency after 28 days was significantly lower in the control group than in the oligosaccharide supplemented group ( p = 0.0079 ) and the reference group ( p stool consistency in the control group became harder , but remained fairly stable in the other two groups . There was no effect of the different diets on the incidence of side effects ( crying , regurgitation , vomiting ) or on weight gain or length gain . Conclusion : Supplementing preterm formula with a mixture of galacto- and fructo-oligosaccharides at a concentration of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in stool characteristics similar to those found in preterm infants fed human milk . Therefore prebiotic mixtures such as the one studied may help to improve intestinal tolerance to enteral feeding in preterm infants", "Background : Human milk components , including oligosaccharides , affect the gastrointestinal flora of infants . Previous studies in adults have demonstrated that fructo-oligosaccharides increase potentially beneficial fecal bacteria , including bifidobacteria . The purpose of this study was to determine the prebiotic effect of infant formula supplemented with fructo-oligosaccharides . Methods : Healthy term infants 2 to 6 weeks of age were enrolled in a 5-week , prospect i ve , r and omized , crossover , single-site study with a nonr and omized human milk comparator group . Washout weeks preceded and followed a week of feeding with fructo-oligosaccharide-supplemented formula ( 1.5 or 3.0 g/L ) . Stool specimens were quantitatively cultured weekly for bacteroides , lactobacilli , bifidobacteria , clostridia and enterococci and were tested for Clostridium difficile toxin . Results : Seventy-two of 87 infants completed the trial ; 58 were formula fed and 14 were human milk fed . Mean counts of bifidobacteria and lactobacilli were similar in all groups at entry and no group experienced a significant change in counts with fructo-oligosaccharide supplementation . After 7 days of fructo-oligosaccharide supplementation the bifidobacteria counts were greater in the 1.5 g/L fructo-oligosaccharide formula group than in the human milk fed or 3.0 g/L fructo-oligosaccharide formula groups . Formula-fed infants had higher counts of enterococci and bacteroides before fructo-oligosaccharide supplementation , and these counts did not change after supplementation . Clostridium counts increased 7 days after supplementation in the 1.5 g/L fructo-oligosaccharide formula group ( P = 0.0356 ) . No human milk fed infants had C. difficile toxin in stools . Fructo-oligosaccharide ( 3.0 g/L ) supplementation result ed in more frequent and significantly softer stools . Conclusions : Infant formula supplemented with 1.5 or 3.0 g/L fructo-oligosaccharides was safe but had minimal effect on fecal flora and C. difficile toxin", "Background : Necrotizing enterocolitis ( NEC ) is one of the most destructive diseases associated with conditions of neonatal prematurity . Supplementation with enteral prebiotics may reduce the incidence of NEC , especially in infants who fed exclusively with breast-milk . Therefore , we compared the efficacy and safety of enteral supplementation of a prebiotic mixture ( short chain galacto-oligosaccharides/long chain fructo-oligosaccharides [ SCGOS/LCFOS ] ) versus no intervention on incidence of NEC in preterm infants . Methods : In a single-center r and omized control trial 75 preterm infants ( birth weight [ BW ] ≤1500 g , gestational age ≤34 weeks and were not fed with formula ) on 30 ml/kg/day volume of breast-milk were r and omly allocated to have enteral supplementation with a prebiotic mixture ( SCGOS/LCFOS ; 9:1 ) or not receive any prebiotic . The incidence of suspected NEC , feeding intolerance , time to full enteral feeds , duration of hospitalization were investigated . Results : Differences in demographic characteristics were not statistically important . SCGOS/LCFOS mixture significantly reduced the incidence of suspected NEC , ( 1 [ 4.0 % ] vs. 11 [ 22.0 % ] ; hazard ratio : 0.49 [ 95 % confidence interval : 0.29 - 0.84 ] ; P = 0.002 ) , and time to full enteral feeds ( 11 [ 7 - 21 ] vs. 14 [ 8 - 36 ] days ; P - 0.02 ] . Also duration of hospitalization was meaningfully shorter in the prebiotic group ( 16 [ 9 - 45 ] vs. 25 [ 11 - 80 ] ; P - 0.004 ] . Prebiotic oligosaccharides were well tolerated by very low BW ( VLBW ) infants . Conclusions : Enteral supplementation with prebiotic significantly reduced the incidence of NEC in VLBW infants who were fed exclusively breast-milk . This finding suggests that it might have been the complete removal of formula which caused a synergistic effect between nonhuman neutral oligosaccharides ( prebiotic ) and human oligosaccharides", "AIM The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various components of breast milk , including prebiotic substances . This prospect i ve double-blind study compared the numbers of bifidobacteria in the stool flora of bottle-fed preterm infants r and omized to receive for 14 days either a formula with prebiotic fructo-oligosaccharides at a concentration of 0.4 g/dL or the same formula with maltodextrin as a placebo . METHODS Within 0 - 14 days after birth , 56 healthy bottle-fed infants were enrolled to receive either the prebiotic or placebo . Faecal sample s were taken at inclusion day and at study day 7 . The number of bifidobacteria in the stools , stool characteristics and somatic growth were recorded during the study . RESULTS In the group fed fructo-oligosaccharides , both the numbers of bifidobacteria in the stools and the proportion of infants colonized with them were significantly higher as compared to the placebo group ( p=0.032 and p=0.030 respectively ) . There was also a higher number of bacteroids in the fructo-oligosaccharide group as compared to the placebo ( p=0.029 ) . At the same time , reduction was noted in the numbers of Escherichia coli and enterococci . ( p=0.029 , and p=0.025 , respectively ) . Supplementation had also significant influence on stool frequency per day ( p=0.0080 ) . CONCLUSION An infant formula containing a small quantity of prebiotic oligosaccharides is well accepted and leads to rapid growth of bifidobacteria in the gut of bottle-fed preterm infants while decreasing the numbers of pathogenic microorganisms", "Background : Premature birth results in a delayed and abnormal qualitative pattern of gut colonization . This abnormal pattern is thought to affect intestinal development and contribute to a higher risk of gastrointestinal infectious diseases such as neonatal necrotizing enterocolitis ( NEC ) . In particular , bifidobacteria are thought to play a major role . We therefore studied bifidobacterial colonization in preterm infants during the first month of life . Patients and Methods : Fecal sample s were prospect ively analyzed in 52 infants born at a gestational age ranging from 30 to 35 weeks fed with a preterm formula alone and , in 18 , with their mother 's milk . Fecal sample s were collected twice per week during the hospital stay . Bifidobacterial colonization was analyzed with culture and a molecular method . Results : Bifidobacterial colonization occurred in 18 infants at a median age of 11 days , always greater than the corrected mean gestational age of 35.4 weeks ( SD , 0.9 ) and greater than 34 weeks for 16 of 18 . Colonization by bifidobacteria was affected by neither birthweight nor mode of delivery nor antibiotics given to the mother or infant . In contrast , birth gestational age had a significant impact on colonization by bifidobacteria ( P Birth gestational age seems to act as a major determinant of bifidobacterial colonization in the premature infant , suggesting the role of gut maturation , a finding that should probably be taken into account in manipulations of the gut flora aim ed at reducing NEC", "OBJECTIVE To determine the association between maternal milk levels of 2-linked fucosylated oligosaccharide and prevention of diarrhea as a result of Campylobacter , caliciviruses , and diarrhea of all causes in breast-fed infants . STUDY DESIGN Data and banked sample s were analyzed from 93 breast-feeding mother-infant pairs who were prospect ively studied during 1988 - 1991 from birth to 2 years with infant feeding and diarrhea data collected weekly ; diarrhea was diagnosed by a study physician . Milk sample s obtained 1 to 5 weeks postpartum were analyzed for oligosaccharide content . Data were analyzed by Poisson regression . RESULTS Total 2-linked fucosyloligosaccharide in maternal milk ranged from 0.8 to 20.8 mmol/L ( 50%-92 % of milk oligosaccharide ) . Moderate-to-severe diarrhea of all causes ( n=77 cases ) occurred less often ( P=.001 ) in infants whose milk contained high levels of total 2-linked fucosyloligosaccharide as a percent of milk oligosaccharide . Campylobacter diarrhea ( n=31 cases ) occurred less often ( P=.004 ) in infants whose mother 's milk contained high levels of 2'-FL , a specific 2-linked fucosyloligosaccharide , and calicivirus diarrhea ( n=16 cases ) occurred less often ( P=.012 ) in infants whose mother 's milk contained high levels of lacto-N-difucohexaose ( LDFH-I ) , another 2-linked fucosyloligosaccharide . CONCLUSION This study provides novel evidence suggesting that human milk oligosaccharides are clinical ly relevant to protection against infant diarrhea", "Breast milk prebiotic oligosaccharides are believed to promote enteral tolerance . Many mothers delivering preterm are unable to provide sufficient milk . We conducted a multicenter , r and omized , controlled trial comparing preterm formula containing 0.8 g/100 mL short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides in a 9:1 ratio and an otherwise identical formula , using formula only to augment insufficient maternal milk volume . Infants were r and omized within 24 h of birth . The primary outcome ( PO ) was time to establish a total milk intake of 150 mL/kg/d PO and the principal secondary outcome ( PSO ) was proportion of time between birth and 28 d/discharge that a total milk intake of ≥150 mL/kg/d was tolerated . Other secondary outcomes included growth , fecal characteristics , gastrointestinal signs , necrotizing enterocolitis , and bloodstream infection . Outcomes were compared adjusted for prespecified covariates . We recruited 160 infants appropriately grown for GA There were no significant differences in PO or PSOs . After covariate adjustment , we showed significant benefit from trial formula in PSO with increasing infant immaturity ( 2.9 % improved tolerance for a baby born at 28-wk gestation and 9.9 % at 26-wk gestation ; p 31-wk gestation . Prebiotic supplementation appears safe and may benefit enteral tolerance in the most immature infants", "AIM To investigate whether a mixture of prebiotic non-digestible oligosaccharides ( GosFos ; referring to galacto- and fructo-oligosaccharides ) would improve feeding tolerance in preterm infants on full enteral formula feeding . We hypothesized that GosFos would : ( 1 ) reduce stool viscosity and ( 2 ) accelerate gastrointestinal transport . METHODS In a placebo-controlled double-blind trial 20 preterm infants on full enteral nutrition ( gestational age 27 ( 24 - 31 ) weeks , postnatal age 42 ( 11 - 84 ) days , and weight at study entry 1570 ( 1080 - 2300 ) g were r and omly allocated to have their feedings supplemented with either GosFos ( 1 g/100 mL ) or placebo for 14 days . Stool viscosity was measured by high-pressure capillary rheometry . Gastrointestinal transport time was assessed as the time from feeding carmine red to its appearance in the diaper . The hypotheses were tested as a priori ordered hypotheses . Data are shown as median ( range ) . RESULTS Birth weight , gestational age , postnatal age , and weight at study entry did not differ between groups . GosFos significantly reduced both stool viscosity , as measured by extrusion force ( 32 ( 2 - 67 ) versus 158 ( 24 - 314 ) N ) , and gastrointestinal transit time ( 12 ( 4 - 33 ) versus 26 ( 5 - 52 ) h ) . No adverse effects were observed . CONCLUSION Formula supplementation with GosFos reduced stool viscosity and accelerated gastrointestinal transport . Further trials are required to investigate whether GosFos facilitates enteral feeding advancement and early enteral nutrition thereby eventually reducing the incidence of catheter-related nosocomial infections and improving long-term outcome", "Objectives The aim of this study was to evaluate the nutritional efficacy and bifidogenic characteristics of a new infant formula containing partially hydrolyzed whey protein , modified vegetable oil with a high & bgr;-palmitic acid content , prebiotic oligosaccharides , and starch . Methods In a double-blind study , healthy formula-fed term infants aged younger than 2 weeks were r and omized to receive either the new infant formula ( NF ) or a st and ard formula ( SF ) until the age of 12 weeks . Anthropometric measurements were taken at enrollment , 6 weeks , and 12 weeks . In a sub sample of infants , blood sample s were taken at 6 weeks and stool sample s were taken at enrollment and 6 weeks . Blood sample s were analyzed for biochemical measures of protein status and amino acids , and stools were analyzed for total bacteria and bifidobacteria . Mothers completed a feeding diary and question naire at 6 and 10 weeks . Results One hundred fifty-four infants were enrolled in the study ; 102 completed the trial . The growth of infants in both formula groups was in line with published growth curves . During the first 6 weeks , NF girls gained more weight and head circumference than the SF girls . These velocity differences were not maintained throughout the 12-week study period . The NF stools had a higher proportion of bifidobacteria at 6 weeks compared with the SF stools , and they were softer . There were no clinical ly significant differences in the blood biochemical and amino acid values between groups . Both formulas were well tolerated by the infants . Conclusions When compared with a st and ard infant formula , the new formula supported satisfactory growth , led to higher counts of bifidobacteria in the feces , produced blood bio-chemical values typical of formula-fed infants , and was well tolerated", "BACKGROUND The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various compounds of breast milk including prebiotic substances . AIM This prospect i ve , double blind , study compared the growth , acceptability and the proportion of bifidobacteria and clostridia in the stool flora of bottle-fed infants r and omized to receive a formula with a specific mixture of 0.4 g/100 ml prebiotic galacto- and long-chain fructooligosaccharides or the same formula without added prebiotics . METHODS Within 0 - 14 days after birth at term , healthy bottle-fed infants were enrolled to receive either a prebiotic formula or a st and ard formula . At recruitment anthropometric measurements were done . These were repeated at the age of 6 and 12 weeks . Stool sample s were taken at inclusion and at the age of 6 weeks . The number of bifidobacteria and clostridia was determined by fluorescent in situ hybridization . RESULTS There was good tolerance of the prebiotic formula . Somatic growth was similar in the two groups . Stool frequency was significantly higher in the prebiotic group ( P=0.031 ) . Infants in the prebiotic group had also softer stools as compared to the control group ( P=0.026 ) . Baseline values of microorganisms at study entry were similar . The percentage of faecal clostridia at the completion of the study was significantly lower in the prebiotic group ( P=0.042 ) , while the proportion of faecal bifidobacteria was higher in the prebiotic group as compared to the control group . However this difference did not reach statistical significance ( P=0.262 ) . The percentage of E. coli was lower in the prebiotic group but again this did not reach statistical significance ( P=0.312 ) . CONCLUSION An infant formula containing prebiotic oligosaccharides is well tolerated , leads to normal somatic growth and suppresses the numbers of clostridia in the faeces with a trend for higher percentage of stool bifidobacteria and lower percentage of E. coli", "The aim of this double-blind , r and omized , placebo-controlled study was to evaluate the effect of a prebiotic mixture on gastric motility in preterm newborns . After a feeding period of 15 days , gastric electrical activity was measured by electrogastrography , and the gastric emptying time was studied by ultrasound technique . No difference was seen in the daily increase of body weight , and no adverse events have been reported . The percentage of time in which propagation was detected in the electrogastrography signal was twice in newborns receiving formula with prebiotics with respect to placebo , and the gastric half-emptying time was 30 % faster in the prebiotic group than the placebo group . Prebiotic oligosaccharides can modulate the electrical activity and the gastric emptying and may improve the intestinal tolerance of enteral feeding in preterm infants", "Objectives : The present study was design ed to evaluate the effect of 2 different combinations of prebiotic ingredients , polydextrose ( PDX ) , galactooligosaccharides ( GOS ) , and lactulose ( LOS ) , at 2 different intake levels on the overall growth and tolerance in healthy term infants up to 120 days of age . Patients and Methods : Healthy , formula-fed , term infants ( n = 226 ) were r and omly assigned to 1 of 3 study formula groups : control group ( n = 76 ) , PG4 group ( control formula supplemented with 4 g/L of a prebiotic blend , n = 74 ) , or PGL8 group ( control formula supplemented with 8 g/L of a prebiotic blend , n = 76 ) . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age , and 24-hour dietary recall and 24-hour tolerance recall were recorded at 30 , 60 , 90 , and 120 days of age . Adverse events were recorded throughout the study . Results : There were no statistically significant differences among the 3 formula groups for weight growth rate or length growth rate at any time point . Significant differences in stool consistency were detected among the 3 formula groups at 30 , 60 , and 90 days of age ( P looser stools than the control group . The PGL8 group had significantly higher stool frequency compared with the control and PG4 groups at 30 days of age ( P = 0.021 and P = 0.017 , respectively ) , but all of the groups were similar at 60 , 90 , and 120 days of age . A statistical difference was detected among the formula groups in 3 categories of adverse events : diarrhea ( control vs PG4 , 4 % vs 18 % , P = 0.008 ) , eczema ( PG4 vs control , 18 % vs 7 % , P = 0.046 ; PG4 vs PGL8 , 18 % vs 4 % , P = 0.008 ) , and irritability ( control vs PGL8 , 4 % vs 16 % , P = 0.027 ) . Conclusions : Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants in comparison with infants fed an unsupplemented formula . A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics", "OBJECTIVE To assess the safety and prebiotic effects of lactulose in preterm infants . STUDY DESIGN This was a prospect i ve , double-blinded , placebo-controlled , single-center study in 23- to 34-weeks premature infants . The study group received 1 % lactulose , and control infants received 1 % dextrose in all feeds ( human milk or formula ) . RESULTS Twenty-eight infants participated ( 15 lactulose , 13 placebo ) . Small doses of lactulose appeared to be safe and did not cause diarrhea . Premature infants on lactulose had more Lactobacilli-positive stool cultures that appeared earlier with larger number of colonies . The lactulose group tended to have less intolerance to enteral feedings , to reach full oral feeds earlier , and to be discharged home earlier . They also tended to have fewer episodes of late-onset sepsis , lower Bell stage necrotizing enterocolitis , and their nutritional laboratory indices were better , especially calcium and total protein . CONCLUSIONS This pilot study supports the safety of supplementing preterm infants ' feeds with low doses of lactulose . It also demonstrated trends that may suggest positive prebiotic effects" ]

[ "The effects of the soluble fiber konjac glucomannan ( GM ) on serum cholesterol concentrations were investigated in 63 healthy men in a double-blind crossover , placebo-controlled study . After a 2-wk baseline period , the subjects were given 3.9 g GM or placebo daily for 4 wk . After a washout period of 2 wk , crossover took place , followed by another 4 wk of treatment . The subjects were encouraged not to change their ordinary diets or general lifestyle during the investigation . GM fibers reduced total cholesterol ( TC ) concentrations by 10 % ( P low-density-lipoprotein cholesterol ( LDL-C ) concentrations by 7.2 % ( P triglycerides by 23 % ( P systolic blood pressure by 2.5 % ( P High-density-lipoprotein cholesterol ( HDL-C ) and the ratio of LDL-C to HDL-C did not change significantly . No change in diastolic blood pressure or body weight was observed . No adverse effects were observed . The results of this study show that GM is an effective cholesterol-lowering dietary adjunct", "BACKGROUND Fiber supplements added to a caloric diet have additional effects on weight reduction in overweight subjects . The aim of this study was to compare the effect of various commercial fiber supplements ( glucomannan , guar gum and alginate ) on weight reduction in healthy overweight subjects . MATERIAL / METHODS One hundred and seventy six men and women were included to receive either active fiber substance or placebo in r and omized placebo-controlled studies . The fiber supplements consisted of the viscous fibers glucomannan ( Chrombalance ) , glucomannan and guar gum ( Appe-Trim ) and glucomannan , guar gum and alginat ( Glucosahl ) . RESULTS All fiber supplements plus a balanced 1200 kcal diet induced significantly weight reduction more than placebo and diet alone , during a five week observation period . However , there were no significant differences between the different fibers in their ability to induce weight reduction , which was approximately 0.8 kg/week ( 3.8 + /- 0.9 , 4.4 + /- 2.0 , 4.1 + /- 0.6 in the Chrombalance , Appe-Trim and Glucosahl group , respectively ) . CONCLUSIONS Glucomannan induced body weight reduction in healthy overweight subjects , whereas the addition of guar gum and alginate did not seem to cause additional loss of weight", "Dietary fibres are frequently used for the treatment of paediatric obesity . The aim of this clinical trial is to evaluate the efficacy of glucomannan in the child obesity management . This experimental design was double blinded with a block r and omisation , alpha = 0.05 , beta = 0.2 and delta = 50 % . The study involved 60 children under 15 years of age ( mean age 11.2 years , mean overweight 46 % ) , 30 of them under glucomannan treatment ( 1 g twice a day for two months ) and 30 under placebo and the same schedule . The drug and the placebo were indistinguishable both for the family and the physician . During the two months study period the children followed a normocaloric diet evaluated every two weeks by a dietetic record book . At the beginning of the study the drug and the placebo groups were comparable in regards to anthropometric data . At the end , the mean overweight of the drug group was decreased from 49.5 % to 41 % and that of the placebo group from 43.9 % to 41.7 % . Both decreases were significant ( p no significant difference was observed between the drug and the placebo groups . The only significant difference concerned the lipid metabolism . The children under glucomannan treatment manifested a significant decrease of alpha-lipoprotein and an increase of pre-beta-lipoprotein and triglycerides ; the children under placebo manifested only a decrease of triglycerides and apo beta-lipoprotein . We suggest that this metabolic alteration may derive from a primary decrease of alpha-lipoprotein , most likely because of an inadequate water intake . ( ABSTRACT TRUNCATED AT 250 WORDS", "Carbohydrate-restricted diets ( CRDs ) promote weight loss , reductions in plasma triacylglycerol ( TAG ) levels , and increases in high-density lipoprotein cholesterol ( HDL-C ) levels but may cause undesirable low-density lipoprotein cholesterol ( LDL-C ) responses in some people . The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease . Using a parallel-arm , double-blind , placebo-controlled design , 30 overweight and obese men ( body mass index , 25 - 35 kg/m(2 ) ) were r and omly assigned to supplement a CRD with soluble fiber ( Konjac-mannan , 3g/d ) ( n = 15 ) or placebo ( n = 15 ) . Plasma lipids , anthropometrics , body composition , blood pressure , and nutrient intake were evaluated at baseline and at 6 and 12 weeks . Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria . Both groups experienced decreases in ( P body weight , percent body fat , systolic blood pressure , waist circumference , and plasma glucose levels . After 12 weeks , HDL-C and TAG improved significantly in the fiber ( 10 % and -34 % ) and placebo ( 14 % , -43 % ) groups . LDL-C decreased by 17.6 % ( P LDL-C reductions were significant in the placebo group only after 12 weeks ( -6.0 % , P LDL-C , adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone . Furthermore , a CRD led to clinical ly important positive alterations in cardiovascular disease risk factors", "AIM This paper evaluates the effect of the adjunct of the hydrosoluble fiber glucomannan to a Step-One-Diet in 40 plasma hypercholesterolemic children , during a r and omized controlled trial , to reduce plasma cholesterol . METHODS All the subjects recruited underwent an 8-week run in diet period ; a Step-One-Diet was prescribed . After that , they were r and omly allocated to one of two groups : Step-One-Diet only ( control ) , and Step-One-Diet plus glucomannan in gelatine capsules . After another 8 weeks of treatment , the results were compared within and between the two groups . RESULTS Glucomannan treated group showed decreased values in plasma total cholesterol ( TC ) and low density lipoprotein cholesterol ( LDL-C ) vs. control group after 8 weeks of treatment . The percentage decrease showed a statistically significant difference between sex groups . Decreases were observed in favor of female vs. male children in TC ( 24 % vs. 9 % ) and LDL-C ( 30 % vs. 9 % ) . CONCLUSIONS These results suggest that glucomannan may represent a rationale adjunct to diet therapy in primary prevention in high risk hypercholesterolemic children", "To evaluate the effectiveness of highly purified glucomannan in childhood obesity a study has been carried out in 23 obese children ( 12 boys and 11 girls , aged 5.2 - 15.8 years ) , with excess weight of 51 + /- 16 % , treated with 2 - 3 caps twice a day of glucomannan fibres ( DICOMAN 5:2 - 3 gr/die ) , and in 30 obese children ( aged 5 - 18 years ) with excess weight of 51 + /- 10 % , studied as controls . After a three-days food recall , a balanced diet with adequate caloric intake was provided to all obese children . In all patients before and 2 - 4 months after the auxological data ( weight , height , weight excess ) and laboratory data ( serum levels of cholesterol , HDL , triglycerides , glucose , fructosamine , glycosylated hemoglobin , RBC , WBC , hemoglobin , iron , calcium , Cu and Zn ) have been determined . Excess weight and triglycerides levels were significantly decreased in treated obese patients than in obese controls 4 months after the beginning of the study . A decrease of cholesterol levels was also observed in treated obese patients , but not in controls , whereas serum iron , calcium , copper and zinc persisted unchanged . No important side-effects were observed in treated patients . On the basis of our results highly purified glucomannan fibres may be employed with effectiveness in obese and dyslipidemic children together with diet", "Objective : The purpose of this study was to determine whether supplements of plant sterols and /or glucomannan improve lipid profile and cholesterol bio synthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments . Design : A r and omized , crossover study consisting of four phases of 21 days , with each phase separated by a 28-day washout . Setting : The Mary Emily Clinical Nutrition Research Unit of McGill University . Subjects : Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38–74 years . Interventions : Subjects were supplemented with plant sterols ( 1.8 g/day ) , glucomannan ( 10 g/day ) , a combination of glucomannan and plant sterols , and a placebo , provided in the form of bars . Results : Overall plasma cholesterol concentrations were lowered ( P ) . Plasma low-density lipoprotein ( LDL ) cholesterol concentrations were decreased ( P of lipid profiles did not differ between subject groups . Overall plasma lathosterol concentrations , an index of cholesterol bio synthesis , were lowered ( P improves plasma LDL cholesterol concentrations . Sponsorship : Forbes Medi-Tech Inc. , Vancouver , British Columbia , Canada", "Objectives : The present study was design ed to evaluate effects of konjac glucomannan ( KGM ) supplement ( 3.6 g/day ) for 28 days on blood lipid and glucose levels in hyperlipidemic type 2 diabetic patients and the possible mechanism for the reductions in blood lipid levels . Methods : Twenty-two diabetic subjects ( age 64.2 + 8.4 years , BMI 25.5 + 3.2 kg/m2 ) with elevated blood cholesterol levels ( fasting glucose between 6.7–14.4 mmol/L ) , but currently not taking lipid-lowering medication , were recruited to participate in a two 28-day period , r and omized , double-blind , crossover clinical trial . Fasting blood sample s drawn on the initial and final days of each period were determined for plasma lipids and glucose levels . Feces collected at the end of each experimental period were analyzed for neutral sterol and bile acid contents . Results : Compared with placebo , KGM effectively reduced plasma cholesterol ( 11.1 % , p = 0.0001 , adjusted α = 0.006 ) , LDL-cholesterol ( 20.7 % , p = 0.0004 , adjusted α = 0.006 ) , total/HDL cholesterol ratio ( 15.6 % , p = 0.0005 , adjusted α = 0.007 ) , ApoB ( 12.9 % , p = 0.0001 , adjusted α = 0.006 ) and fasting glucose ( 23.2 % , p = 0.002 , adjusted α = 0.008 ) . Plasma triglyceride , HDL-cholesterol , LDL/HDL cholesterol , postpr and ial glucose and body weight were not significant after adjustment by the Bonferroni-Hochberg procedure . Fecal neutral sterol and bile acid concentrations were increased by 18.0 % ( p = 0.004 ) and 75.4 % ( p with KGM supplement . Conclusions : The KGM supplement improved blood lipid levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in diabetic subjects . KGM could be an adjunct for the treatment of hyperlipidemic diabetic subjects", "An eight-week double-blind trial was conducted to test purified glucomannan fiber as a food supplement in 20 obese subjects . Glucomannan fiber ( from konjac root ) or placebo was given in 1-g doses ( two 500 mg capsules ) with 8 oz water , 1 h prior to each of three meals per d. Subjects were instructed not to change their eating or exercise patterns . Results showed a significant mean weight loss ( 5.5 lbs ) using glucomannan over an eight-week period . Serum cholesterol and low-density lipoprotein cholesterol were significantly reduced ( 21.7 and 15.0 mg/dl respectively ) in the glucomannan treated group . No adverse reactions to glucomannan were reported", "OBJECTIVE To evaluate the benefits of glucomannan supplement on glycemic and lipid controls in type 2 diabetic patients . MATERIAL AND METHOD A single-blind , placebo-controlled , crossover trial with two treatments separated by a 2-week washout period was performed in 10 men and 10 women with type 2 diabetes mellitus . Two separated protocol s of experiments were sequentially followed . Initially , purified glucomannan ( 1 g ) or placebo was ingested 30 min before 75-g glucose load to evaluate their effects on glucose absorption and insulin secretion in oral glucose tolerance test ( OGTT ) . Later , the glycemic and lipid changes after 4-week intervention with 3 g/day glucomannan comparing to the placebo were determined . The st and ard OGTT was performed before and after ending of each intervention . RESULTS Glucomannan taken before performing the OGTT can lower the rise of blood glucose and insulin from 1 to 2 hour in comparison with the placebo , though a statistically significance of insulin was not achieved . Long-term glucomannan supplement significantly reduced the 120-min glucose area under the curve of OGTT . Glucomannan also decreased the rise of low-density lipoprotein cholesterol ( LDL-C ) . Reductions of HOMA-insulin resistance index and body mass index were detected in glucomannan-treated group though the former was shown only in females . No within- and between-group differences of insulin , fructosamine , and other lipids were observed in glucomannan- nor placebo- treated groups . CONCLUSION In type 2 diabetes , pre-pr and ial glucomannan ingestion attenuated a rise of blood glucose without significantly affecting insulin levels . Long-term supplement of glucomannan to the regular diabetic regimen lessened post challenge glucose AUC and impeded the rise of LDL-C. Supplement of glucomannan may be beneficial to the glycemic and lipid controls in type 2 diabetes mellitus", " Two groups of 25 severely obese patients underwent 3 months of hypocaloric diet therapy either alone or associated with a glucomannan-based fibrous diet supplement ( approx . 4 g/die in 3 doses ) . The comparative analysis of the results obtained in both groups showed that the diet + glucomannan group had a more significant weight loss in relation to the fatty mass alone , an overall improvement in lipid status and carbohydrate tolerance , and a greater adherence to the diet in the absence of any relevant side effects . Due to the marked ability to satiate patients and the positive metabolic effects , glucomannan diet supplements have been found to be particularly efficacious and well tolerated even in the long-term treatment of severe obesity" ]

[ "The aims of this study were 1 ) to evaluate whether subjects suffering from acute mountain sickness ( AMS ) during exposure to high altitude have signs of autonomic dysfunction and 2 ) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS . Forty-one mountaineers were studied at 4,559-m altitude . AMS was diagnosed using the Lake Louise score , and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure ( BP ) variability on 10-min resting recordings . Seventeen subjects ( 41 % ) had AMS . Subjects with AMS were older than those without AMS ( P low-frequency ( LF ) component of systolic BP variability ( LF(SBP ) ) was higher ( P = 0.02 ) and the LF component of R-R variability in normalized units ( LF(RR)NU ) was lower ( P = 0.001 ) in subjects with AMS . After 3 mo , 21 subjects ( 43 % with AMS ) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture . LF(RR)NU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude ( P Conversely , LF(SBP ) increased significantly during short-term hypoxia only in subjects with AMS , who also had higher resting BP ( P LF(SBP ) response to short-term hypoxia identifies AMS-prone subjects , supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS", "OBJECTIVE : Although a history of previous acute mountain sickness ( AMS ) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure , the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospect i ve controlled study . METHODS : In 27 nonacclimatized children and 29 adults , AMS was assessed during the first 48 hours after rapid ascent to 3450 m on 2 consecutive occasions 9 to 12 months apart . RESULTS : During the first exposure , 18 adults ( 62 % ) and 6 children ( 22 % ) suffered from AMS ; during the second exposure , 14 adults ( 48 % ) and 4 children ( 15 % ) suffered from this problem ( adults versus children , P ≤ .01 ) . Most importantly , the intraindividual reproducibility of AMS was very different ( P children having suffered from AMS during the first exposure suffered from AMS during the second exposure , but 4 children with no AMS during the first exposure did experience this problem during the second exposure . In contrast , 14 of the 18 adults who suffered from AMS on the first occasion also presented with this problem during the second exposure , and no new case developed in those who had not experienced AMS on the first occasion . CONCLUSIONS : In adults , a history of AMS is highly predictable of the disease on subsequent exposure , whereas in children it has no predictive value . A history of AMS should not prompt practitioners to advise against reexposure to high altitude or to prescribe drugs for its prophylaxis in children", "Study Objective : Despite causing significant morbidity throughout the mountainous regions of the world , the pathophysiology of acute mountain sickness ( AMS ) remains poorly understood . This study aims to improve the underst and ing of altitude illness by determining if vascular endothelial growth factor ( VEGF ) plays a role in the development of AMS . The purpose of this study was to determine if elevated plasma VEGF correlates with increased symptoms of AMS at high altitude . Patients and Methods : This is a prospect i ve study of a cohort of healthy climbers on Denali ( Mount McKinley ) in Alaska at 14 , 200 feet . Baseline demographics , medications , rates of ascent , and AMS scores were recorded . Pulse oximetry measurements and venous blood sample s were obtained . Comparisons were made between mountaineers with and without AMS . Results : Seventy-two climbers were approached for participation in the study ; 21 ( 29 % ) refused . Of the 51 climbers participating in the study , 14 subjects ( 27.5 % ) had symptoms of AMS and 37 subjects ( 72.5 % ) were free of symptoms of AMS . Plasma VEGF levels were 79.14 pg/dl ( SD : 121.44 ) and 57.57pg/dl ( SD : 102.71 ) in the AMS and non-AMS groups , respectively . These results were nonsignificant . Similarly , comparison of sex , age , rate of ascent , pulse oximetry values , or history of altitude illness did not reveal significant differences between the AMS and non-AMS groups . Conclusion : This study does not provide evidence in support of the theory that plasma VEGF correlates with symptoms of AMS", "Forty-seven climbers participated in a double-blind , r and omized trial comparing acetazolamide 250 mg , dexamethasone 4 mg , and placebo every eight hours as prophylaxis for acute mountain sickness during rapid , active ascent of Mount Rainier ( elevation 4,392 m ) . Forty-two subjects ( 89.4 percent ) achieved the summit in an average of 34.5 hours after leaving sea level . At the summit or high point attained above base camp , the group taking dexamethasone reported less headache , tiredness , dizziness , nausea , clumsiness , and a greater sense of feeling refreshed ( p less than or equal to 0.05 ) . In addition , they reported fewer problems of runny nose and feeling cold , symptoms unrelated to acute mountain sickness . The acetazolamide group differed significantly ( p less than or equal to 0.05 ) from other groups at low elevations ( 1,300 to 1,600 m ) , in that they experienced more feelings of nausea and tiredness , and they were less refreshed . These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness . Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone . This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease" ]

[ "Abstract . This study documented postoperative morbidity during the first 4 months following anterior cruciate ligament ( ACL ) reconstruction using either patellar tendon or hamstring tendon autograft . Sixty-five patients undergoing primary arthroscopically assisted single-incision ACL reconstruction were r and omized to have a central third bone patellar tendon bone autograft ( PT ) or a doubled semitendinosus/doubled gracilis autograft ( HS ) . Postoperatively patients undertook a st and ard ' accelerated ' rehabilitation protocol . Patients were review ed after 2 weeks , 8 weeks , and 4 months . At each review the location and severity of general knee pain and the presence and severity of anterior knee pain ( AKP ) were recorded as were the presence and size of an effusion as well as the active and passive flexion and passive extension deficits compared to the contralateral limb . Pain on kneeling , KT-1000 measured side to side difference in anterior tibial displacement , isokinetic assessment of quadriceps and hamstring peak torque deficits , IKDC score and Cincinnati sports activity level were also recorded after 4 months . After 2 weeks more patients in the PT group complained of AKP and reported that the pain was more severe . After 8 weeks there was no significant difference between the groups for any variable . After 4 months the severity of general pain experienced and the incidence of pain on kneeling were greater in the PT group . The PT group also demonstrated a significantly greater quadriceps peak torque deficit at 240 ° /s . IKDC scores were higher in the HS group , but Cincinnati sports activity scores were higher in the PT group . Although we observed a lower morbidity in the HS group , primarily related to pain , the severity of pain in both groups was relatively low and , in light of the higher mean sports activity level observed in the PT group at 4 months the clinical impact of the difference may not be significant", "BACKGROUND There are no controlled , prospect i ve studies comparing the 10-year outcomes of anterior cruciate ligament ( ACL ) reconstruction using patellar tendon ( PT ) and 4-str and hamstring tendon ( HT ) autografts . HYPOTHESIS Comparable results are possible with HT and PT autografts . STUDY DESIGN Cohort study ; Level of evidence , 2 . METHODS One hundred eighty ACL-deficient knees that met inclusion criteria underwent ACL reconstruction ( 90 HT autograft , 90 PT autograft ) by one surgeon and were treated with an accelerated rehabilitation program . All knees were observed in a prospect i ve fashion with subjective , objective , and radiographic evaluation at 2 , 5 , 7 , and 10-year intervals . RESULTS At 10 years , there were no differences in graft rupture rates ( 7/90 PT vs. 12/90 HT , P = .24 ) . There were 20 contralateral ACL ruptures in the PT group , compared with 9 in the HT group ( P = .02 ) . In all patients , graft rupture was associated with instrumented laxity > 2 mm at 2 years ( P = .001 ) . Normal or near-normal function of the knee was reported in 97 % of patients in both groups . In the PT group , harvest-site symptoms ( P = .001 ) and kneeling pain ( P = .01 ) were more common than in the HT group . More patients reported pain with strenuous activities in PT knees than in HT knees ( P = .05 ) . Radiographic osteoarthritis was more common in PT knees than the HT-reconstructed knees ( P = .04 ) . The difference , however , was composed of patients with mild osteoarthritis . Other predictors of radiographic osteoarthritis were single-legged hop test at 1 year and the need for further knee surgery . An \" ideal \" outcome , defined as an overall International Knee Documentation Committee grade of A or B and a radiographic grade of A at 10 years after ACL reconstruction , was associated with mm of instrumented laxity at 2 years , the absence of additional surgery in the knee , and HT grafts . CONCLUSIONS It is possible to obtain excellent results with both HT and PT autografts . We recommend HT reconstructions to our patients because of decreased harvest-site symptoms and radiographic osteoarthritis", "Two commercially available knee ligament arthrometers ( KT-1000 MEDmetric Corporation , San Diego , California and Kneelax MR Systems , Haarlem , The Netherl and s ) were used to measure anterior tibial translation . In this study 91 subjects with no history of knee pathology were tested using both devices . Both normal knees were tested and comparison of recorded anterior translation ( millimeters ) was performed . Absolute numbers at forces of 67N , 89N , 134N , and manual maximum displacements were recorded . Side-to-side differences were calculated and data were compared . There was a significant difference found between the absolute values of each device . The KT-1000 was found to record greater values in millimeters of translation . Although the absolute values were significantly different , the side-to-side differences were not significantly different between devices", "Background : Numerous studies have compared patellar tendon ( PT ) and hamstring tendon ( HS ) anterior cruciate ligament ( ACL ) reconstructions in the short to midterm , but fewer long-term results have been published . Hypothesis : There will be no difference in functional outcome between ACL reconstruction performed with PT and HS grafts , but PT grafts will have more donor site morbidity . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Sixty-five patients undergoing ACL reconstruction were r and omized to receive either a PT graft or a 4-str and HS graft . Early results were reported at 4 , 8 , 12 , 24 , and 36 months . Forty-seven patients ( 22 of 31 PT and 25 of 34 HS ) were review ed at a mean of 15.3 years . Results : Four graft ruptures ( 1 PT , 3 HS ) and 6 contralateral ACL injuries ( 4 PT , 2 HS ) occurred in the group that was review ed . There was no statistically significant difference between the groups for any of the variables measured . There was a similar incidence of anterior knee pain and kneeling pain in both groups . The previously observed increased extension deficit in the PT group at 3 years was not present at 15 years , and there was no significant between-group difference in knee laxity . A higher proportion of patients in the PT group were participating in sport on a weekly basis ( 73 % PT , 48 % HS ; P = .05 ) . There was no difference in the degree of osteoarthritis between the groups . Conclusion : This r and omized controlled trial showed that HS and PT ACL reconstructions have comparable results at an average 15-year follow-up . Contrary to the study hypothesis , some of the graft differences seen at earlier review were not present at 15 years , and patients with PT grafts were more active in sport participation . Overall , both graft types provided good long-term subjective and objective outcomes", "Background : Short-term and mid-term differences between hamstring and patellar tendon autografts for anterior cruciate ligament ( ACL ) reconstruction are well documented . Systematic review s highlight the lack of long-term results between the two grafts . Hypothesis : Seventeen years after ACL reconstruction , no difference will be found in functional outcome , quality of life , and graft failure between patients with patellar tendon ( PT ) or semitendinosus and gracilis tendon ( STG ) autografts ; however , a significant difference will be seen in the prevalence of osteoarthritis . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : Sixty-four patients were included in this prospect i ve study ( 32 in each group ) . A single surgeon performed primary ACL reconstruction in alternating sequence . Forty-eight patients ( 24 in each group ) were evaluated 17 years after ACL reconstruction : A clinical assessment was made based on the International Knee Documentation Committee ( IKDC ) form , instrumented laxity was measured with KT-1000 arthrometer , and radiography of the operated knee was conducted and assessed for degenerative disease . The Lysholm question naire and the Short Form–36 version 2 question naire were filled out by the patients . Results : At the 17-year follow-up , no statistically significant differences were seen with respect to graft failure ( 2 reruptures in the semitendinosus and gracilis tendon [ STG ] group [ 6.3 % ] and 3 reruptures in the PT group [ 9.4 % ] ) and functional outcome . Increased instrumented laxity ( > 3 mm ) measured with KT-1000 arthrometer was seen in significantly more patients in the STG group ( 8 in the STG group compared with 2 in the PT group ; P = .03 ) with a mean side-to-side difference of 2.17 ± 1.86 mm in the STG group compared with 1.33 ± 1.93 mm in the PT group . A significant difference was found in frequency of knee osteoarthritis (OA)—100 % in the PT group compared with 71 % in the STG group ( P = .004 ) . Patients in the PT group tended to have higher grade OA according to the IKDC grading system , with an average grade of 1.46 in the PT group compared with 1 in the STG group ( P = .055 ) . The degenerative changes in the PT group were more common in the medial and patellofemoral compartments ( P = .003 and P = .04 , respectively ) . Conclusion : Both autografts provided good to excellent subjective outcomes . No significant differences were noted in graft failure and clinical instability . However , significantly more patients in the STG group had increased instrumented anteroposterior translation measured with KT-1000 arthrometer , and there was a greater prevalence of knee OA at 17 years after surgery in the PT group", "Background Functional outcome question naires have become a common part of patient follow-up in the orthopaedic community . The modified Cincinnati Knee Rating System and the International Knee Documentation Committee ( IKDC ) subjective scale were design ed to provide clinicians with information regarding a patient ’s functional and clinical status after knee surgery . Hypothesis The functional outcome data reported on the modified Cincinnati Knee Rating System and the IKDC subjective question naire are equivalent . Study Design Cohort study ( diagnosis ) ; Level of evidence , 2 . Methods Between 2000 and 2007 , all patients with complex knee disorders seen in our orthopaedic clinic were prospect ively followed and given simultaneously the modified Cincinnati Knee Rating System and the IKDC subjective question naires to report their functional outcomes . The total scores of each instrument were compared at each time of evaluation . As a measure of responsiveness , the st and ardized response means were calculated . A second within-patient analysis was also performed to determine if the results would be different when looked at by the patient . Results There were a total of 130 patients with a total of 444 modified Cincinnati Knee Rating System question naires and 462 IKDC subjective complete question naires included in the study . Overall total scores on both the modified Cincinnati Knee Rating System and the IKDC subjective question naires were equivalent in a population analysis . Overall total scores showed improvement in function over time from preoperative measurement through the 2-year follow-up . The individual patient analysis demonstrated that , for a specific patient , it was possible that up to 34 % of the population would report a total score of more than 10 points difference , depending on the scale selected . Conclusion The modified Cincinnati Knee Rating System and the IKDC subjective rating question naires reported by patient population provide similar results . The practitioner who is not performing a population -based study but following individual patients for recovery will find that the individual question naires may offer different functional limitations . Individual differences were lost in the population means , with the approximate balance of positive and negative score differences masking the individual patient differences", "PURPOSE To evaluate the subjective outcomes , knee stability , and donor-site morbidity after revision ACL reconstruction using either autologous ipsilateral quadriceps tendon or contralateral semitendinosus-gracilis tendon . METHODS A sample size calculation suggested that we needed 25 patients in each group to detect e quality between both groups . Therefore , we evaluated 30 consecutive patients who underwent an ACL revision surgery with ipsilateral bone-quadriceps tendon grafts and 30 consecutive patients with the contralateral semitendinosus-gracilis grafts between January 2010 and December 2012 . Because of follow-up and exclusion criteria , finally 51 patients were evaluated . All patients were followed prospect ively for at least 2 years with KT1000 arthrometer testing and the International Knee Documentation Committee ( IKDC ) objective grading . At the 24-month follow-up , additional clinical scores were evaluated : the Knee Injury Osteoarthritis Outcome Score ( KOOS ) , the Lysholm score , assessing pain during kneeling , and anterior knee pain . RESULTS The KT1000 postoperative arthrometer side-to-side difference was 2.0 ± 1.2 mm for the quadriceps group and 3.0 ± 2.9 mm for the semitendinosus-gracilis group . The difference was not statistically significant ( P = .461 ) . There was also no difference in the rate of positive pivot-shift tests between groups ( P = .661 ) . The Lysholm score was 82.5 ± 18 in the quadriceps group and 73.8 ± 19 in the semitendinosus-gracilis group . The difference was not statistically significant ( P = .060 ) . There was also no significant difference in the single KOOS subscores , assessing pain while kneeling and anterior knee pain ( included in the KOOS score ) . No rerupture occurred during follow-up . CONCLUSIONS Revision ACL reconstruction using the quadriceps tendon graft showed clinical outcomes similar to those of the contralateral semitendinosus-gracilis graft in terms of knee stability and function . Thus , the bone-quadriceps tendon graft may be a good alternative to the contralateral semitendinosus-gracilis tendon graft for revision ACL reconstruction . LEVEL OF EVIDENCE Level II , prospect i ve comparative study", "ACL reconstruction with bone patellar tendon bone ( BPTB ) grafts has been shown to produce dependable results . Recently , reconstructions with double-looped semitendinosus gracilis ( DLSG ) grafts have become common . The prevailing opinion is that ACL reconstruction with patellar tendon graft produces a more stable knee with more anterior knee pain than DLSG grafts , while the functional results and knee scores are similar . The present study evaluates BPTB grafts fixed with metallic interference screws and DLSG grafts fixed with Bone Mulch Screw on the femur and WasherLoc fixation on the tibia . All else being the same , there is no difference in the outcome between the two grafts and fixation methods . This is a prospect i ve r and omized multicenter study . A total of 115 patients with isolated ACL ruptures were r and omized to either reconstruction with BPTB grafts fixed with metal interference screws ( 58 patients ) or DLSG grafts ( 57 patients ) fixed with Bone Mulch Screws and WasherLoc Screws . Follow-up was at one and two years ; the latter by an independent observer . At two years , one ACL revision had been performed in each group . Eight patients in the DLSG group and one in the BPTB group underwent meniscus surgery in the follow-up period ( P = 0.014 ) . Mean Lysholm score at the two year follow-up was 91 ( SD ± 10.3 ) in the DLSG group and also 91 ( SD ± 10.2 ) in the BPTB group . Mean KT-1000 at two years was 1.5 mm in the BPTB group and 1.8 mm in the DLSG group ( n.s . ) . At two years , four patients in the BPTB group and three in the DLSG group had a Lachman test grade 2 or 3 ( n.s . ) . More patients in the BPTB group had pain at the lower pole of the patella ( P = 0.04 ) . Peak flexion torque and total flexion work were lower in the DLSG group at one year ( P = 0.003 and P = 0.000 ) and total flexion work also at two years ( P = 0.05 ) . BPTB ACL reconstruction fixed with interference screws and DLSG fixed with Bone Mulch Screws on the femur and WasherLoc Screws on the tibia produce satisfactory and nearly identical outcomes . Among our patients in the DLSG group , flexion strength was lower , and more patients underwent meniscus surgery in the follow-up period . The BPTB group has more anterior knee pain", "Purpose Graft choice for anterior cruciate ligament ( ACL ) reconstruction is crucial , however the optimal graft source remains a topic of controversy . The purpose of this study is to compare subjective and functional patient-reported outcomes ( PRO ) after single-bundle ACL reconstruction using quadriceps tendon ( QT ) or hamstring tendon ( HT ) autografts for single-bundle ACL reconstruction . We hypothesize that there is no difference in patient-reported functional outcomes after ACL reconstruction using either HT- or QT autograft . Methods All data were extracted from a prospect ively collected ACL registry . A total of 80 patients with at least 2-year follow-up were included in this study . A total of 40 patients with primary ACL reconstruction using a QT autograft harvested via a minimally invasive technique were matched by sex , age and pre-injury Tegner and Lysholm score to 40 patients who received HT autografts . Subjective and functional PRO scores including Lysholm score , Tegner activity level and visual analogue scale for pain were obtained at 6 , 12 and 24 months after index surgery . Results No significant difference between the QT and the HT group was seen at any follow-up in regard to any of the PRO scores for function or pain . 24 months post-surgery the mean Tegner activity score of the HT group was significantly ( p = 0.04 ) lower compared to the pre-injury status . At final follow-up , 27 patients ( 67.5 % ) in the QT group and 32 patients ( 80.0 % ) in the HT returned to their pre-injury activity level ( n.s . ) . A total of 37 patients ( 92.5 % ) of the QT cohort and 35 patients ( 87.5 % ) of the HT cohort reported “ good ” or “ excellent ” results according to the Lysholm score ( n.s . ) . “ No pain ” or “ slight pain ” during severe exertion was reported by 33 patients ( 82.5 % ) with QT autograft and 28 patients ( 82.4 % ) with HT autograft ( n.s . ) . Conclusion There is no significant difference between PRO 2 years post-operative using either QT or HT autografts . Both QT and HT grafts show acceptable and comparable PRO scores making the QT a reliable graft alternative to HT for primary ACL reconstruction . Level of evidence III", "BACKGROUND The comparison between HT and QT grafts in strength recovery and function after an ACLR is scarce in the literature . METHODS A total of 56 participants were enrolled in this r and omized controlled trial and placed into two groups : HT or QT . The hamstring/quadriceps ( H/Q ) ratio was the primary end-point measured with a Genu-3 dynamometer . Peak torque , functional assessment ( Lysholm knee scoring scale and Cincinnati Knee Rating System ) , and anteroposterior laxity ( KT-2000 ™ arthrometer ) were also assessed . An intention-to-treat analysis was performed . RESULTS The results of the H/Q ratio analysis of the participants over time revealed significant differences at 60 , 180 , and 300 ° /s at three , six , and 12months of follow-up ( 60 ° /s : F=5.3 , p=0.005 ; 180 ° /s : F=5.5 , p=0.004 ; 300 ° /s : F=5.1 , p=0.005 ) . Furthermore , they revealed significant differences at 60 ° /s , 180 ° /s , and 300 ° /s in the participants over time for peak torque in the extensor muscle strength at three and six months of follow-up , with higher values in the hamstring tendon group but not at 12months of follow-up . There were no significant differences in functional endpoints or arthrometer assessment s at 24months of follow-up . CONCLUSION An ACLR with a QT graft showed similar functional results with a better isokinetic H/Q ratio compared to an ACLR with the HT at 12months of follow-up in soccer players . This higher H/Q ratio observed with the QT could be an advantage of this graft over the HT for an ACLR", "Objective : To compare 3 anatomically positioned autografts for anterior cruciate ligament ( ACL ) reconstruction , by measuring patient-reported disease-specific quality of life at 2 years postoperatively . Design : Double-blinded , r and omized clinical trial with intraoperative computer-generated treatment allocation . Patients and an independent trained evaluator were blinded . Setting : University-based orthopedic referral practice . Patients : Three hundred thirty patients ( 14 - 50 years ; 183 male patients ) with isolated ACL deficiency were equally r and omized to : ( 1 ) patellar tendon , PT : 28.7 years ( SD = 9.7 ) ; ( 2 ) quadruple-str and ed hamstring tendon , HT : 28.5 years ( SD = 9.9 ) ; and ( 3 ) double bundle using HT , DB : 28.3 years ( SD = 9.8 ) ; 322 patients completed 2-year follow-up . Intervention : Anterior cruciate ligament reconstruction using PT , HT , or DB autografts . Main Outcome Measures : Measured at baseline , 1 and 2 years postoperatively— primary : anterior cruciate ligament quality -of-life scores ; secondary : International Knee Documentation Committee ( IKDC ) scores , KT-1000 arthrometer , pivot shift , range of motion , Tegner activity , Cincinnati Occupational Scale , and single-leg hop . Proportions of correct graft type guesses by the patients and evaluator assessed blinding effectiveness . Results : Baseline characteristics were not different . Anterior cruciate ligament quality -of-life scores increased over time for all groups ( P = 0.001 ) but were not different at 2 years ( P = 0.591 ) : PT = 84.6 ( SD = 16.6 , 95 % confidence interval [ CI ] = 81.4 - 87.8 ) , HT = 82.5 ( SD = 17.7 , 95 % CI = 79.2 - 85.9 ) , and DB = 82.4 ( SD = 17.5 , 95 % CI = 79.1 - 85.7 ) . Two-year KT-1000 side-to-side differences ( PT = 1.86 mm ; HT = 2.97 mm ; DB = 2.65 mm ) were statistically significant between PT – HT ( P = 0.002 ) and PT – DB ( P = 0.044 ) . The remaining secondary outcomes were not statistically different . Correct graft type guesses occurred 51 % of the time for patients and 46 % for the evaluator . Conclusions : Two-year disease-specific quality -of-life outcome was not different between the ACL reconstruction techniques . The PT reconstructions had significantly lower side-to-side differences on static stability measures . Patient and evaluator blinding was achieved . Level of Evidence : Level 1 ( Therapeutic Studies ) . Clinical Relevance : This high- quality , large , double-blind r and omized clinical trial ( RCT ) addresses the insufficient evidence in the literature comparing PT , single-bundle hamstring , and DB hamstring reconstructions for ACL rupture in adults . In addition to the clinical and functional results , this RCT uniquely reports on the disease-specific , patient-reported quality -of-life outcome at 2 years postoperatively", "BACKGROUND The aim of the study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third bone-patellar tendon-bone ( BTB ) autografts and triple/quadruple semitendinosus ( ST ) autografts . HYPOTHESIS In the long-term , ACL reconstruction using BTB autografts will render more donor-site problems than ST autografts . STUDY DESIGN R and omized controlled trial ; Level of evidence , 1 . METHODS A r and omized series of 71 patients ( 22 women and 49 men ) with a unilateral ACL rupture who underwent reconstructive surgery were included in the study . The BTB graft was used in 34 patients ( BTB group ) and the ST-tendon graft was used in 37 patients ( ST group ) . The patients were examined a median of 86 months ( range , 68 to 114 months ) after the reconstruction . RESULTS Sixty-eight of 71 patients ( 96 % ) were examined at follow-up . The clinical assessment s at follow-up revealed no significant differences between the BTB group and the ST group in terms of the Lysholm score , Tegner activity level , International Knee Documentation Committee evaluation system , 1-legged hop test , KT-1000 arthrometer laxity measurements , manual Lachman test , and range of motion . A significant improvement was seen in both groups compared with the preoperative values in terms of most clinical assessment s. Donor-site morbidity in the form of knee-walking ability , kneeling ability , and area of disturbed anterior knee sensitivity revealed no significant differences between the groups . CONCLUSION Seven years after ACL reconstruction , the subjective and objective outcomes were similar after using the central -third BTB autograft and triple/quadruple ST autograft . Furthermore , no difference in terms of donor-site morbidity was found between the 2 groups", "PURPOSE OF THE STUDY The aim of this prospect i ve study was to evaluate functional outcomes and knee joint stability after double-bundle anterior cruciate ligament reconstruction using three-tunnel quadriceps tendon-bone graft and four-tunnel hamstring graft ( semi-tendinosus and gracilis muscles ) . MATERIAL Group 1 included 20 patients undergoing reconstruction with quadriceps tendon- bone graft group ; 2 comprised of 20 patients treated by hamstring graft . There were 26 men and 14 women , with an average age of 27 ( range , 16 to 44 ) years . The minimum follow-up period was one year . METHODS In group 1 patients , semi-anatomic anterior cruciate ligament reconstruction was performed by a three-tunnel technique ( two tunnels in the femur and one in the tibia ) using quadriceps femoris muscle graft . Group 2 patients were treated by anatomic four-tunnel reconstruction ( two tunnels in the femur and two in the tibia ) with the use of hamstring graft . Functional outcomes were evaluated on the basis of Lysholm and IKDC scores . Antero-posterior stability was measured with aKT-1000 arthrometer and rotational stability was assessed by the pivot-shift test . For statistical evaluation , the level of significance ( p ) was set at average Lysholm score of 88.9 ± 12 ( 76 - 100 ) points for group 1 , and 87.9 ± 11 ( 62 - 100 ) points for group 2 ; there was no statistically significant difference . The rounded average result of the functional IKDC score after surgery was the same in the two groups ( 80 ± 10 ) . The joints treated by the three-tunnel technique had on average better antero-posterior stability , but this was not statistically significant . The pivot-shift phenomenon was not seen in either of the groups . Operative times in both groups were comparable . An intra-operative fracture of the patella occurred in two patients of group 1 . DISCUSSION No similar prospect i ve study comparing the outcomes of the methods reported here has been found in the internatio- nal literature . The studies so far published have not included any such comparison or they compared other techniques , such as single- versus double-bundle reconstructions . CONCLUSIONS Based on Lysholm and IKDC score evaluation and antero-posterior and rotational stability assessment , it can be concluded that both the three- and the four-tunnel technique of anterior cruciate ligament reconstruction gave similar results , with no significant differences , at one-year follow-up . However , these are only short-term results and only a long-term follow-up can prove or disprove the validity of this conclusion", "BACKGROUND The choice of graft for anterior cruciate ligament reconstruction is a matter of debate , with patellar and hamstring tendons being the two most popular autologous graft options . The objective of this study was to determine in a prospect i ve , r and omized clinical trial whether two grafts ( bone-patellar tendon-bone or doubled hamstring tendons ) fixed with modern devices affect the two-year minimum clinical and radiographic outcomes of anterior cruciate ligament reconstruction . METHODS One hundred and twenty patients with a chronic unilateral rupture of the anterior cruciate ligament underwent arthroscopically assisted reconstruction with use of either autologous bone-patellar tendon-bone or doubled hamstring tendon grafts , in a strictly alternating manner . Both groups were comparable with regard to demographic data , preoperative activity level , mechanism of injury , interval between the injury and the operation , and the amount of knee laxity present preoperatively . The same well-proven surgical technique and aggressive controlled rehabilitation was used . An independent observer , who was blinded with regard to the involved leg and the type of graft , performed the outcome assessment with use of a visual analog scale , the new International Knee Documentation Committee form , the Knee Injury and Osteoarthritis Outcome Score , the Functional Knee Score for Anterior Knee Pain , and an arthrometric and an isokinetic dynamometric evaluation . Radiographs were also made . RESULTS At the two-year follow-up evaluation , no differences were found in terms of the visual analog score , the Knee Injury and Osteoarthritis Outcome Score , the new International Knee Documentation Committee subjective and objective evaluation scores , the KT-1000 side-to-side laxity measurements , the Functional Knee Score for Anterior Knee Pain , muscle strength recovery , or return to sports activities . In the bone-patellar tendon-bone group , we found a higher prevalence of postoperative kneeling discomfort ( p skin sensitivity ( p femoral tunnel widening ( p pivot-shift glide ( p = 0.035 ) . CONCLUSIONS We believe that , with use of accurate and proven surgical and rehabilitation techniques , both grafts are an equivalent option for anterior cruciate ligament reconstruction", "Purpose The purpose of this article was to demonstrate an anterior cruciate ligament ( ACL ) reconstruction technique using oval tunnels . Aim of this single bundle technique is to fit the footprint anatomy of the ACL as closely as possible . Technique and patients The presented technique is a single bundle technique using a semitendinosus graft . For femoral tunnel placement , a specific medial portal aim er ( Karl Storz , Tuttlingen , Germany ) is used . Aim ing and drilling of the femoral tunnel are performed via the medial portal . Oval tunnels are created by stepwise dilatation with ovally shaped dilatators . The position of the femoral tunnel is visualized and controlled with the arthroscope via the medial portal . For the tibial tunnel placement , a specific aim er was used as well . With this technique , 24 patients were operated and all intra- and postoperative complications were analyzed prospect ively . The tunnel position was documented postoperatively by CT scan . Results There were no significant intra- and postoperative complications associated with the oval tunnel technique . The postoperative 3D CT scan revealed that all femoral and tibial tunnels were located within the area of the anatomical ACL insertions . Conclusions This article presents an ACL reconstruction technique using oval dilatators and medial portal aim ers to create oval tunnels . These oval tunnels match the insertion site anatomy much closer than round tunnels do . Level of Evidence Level IV , case series", "Background : The quadriceps tendon ( QT ) autograft is known as an effective graft for anterior cruciate ligament ( ACL ) reconstruction and shows a similar functional outcome to the bone-patellar tendon-bone ( BPTB ) in r and omized controlled trials , with a lesser incidence of complications . Up until now , only 2 studies have compared QT to hamstring tendon ( HT ) autograft . Hypothesis : The functional outcomes of the QT technique are at least as good as those of the HT technique , with the same morbidity . Study Design : Cohort study ; Level of evidence , 3 . Methods : Ninety-five patients underwent isolated ACL reconstruction between January 1 and December 31 , 2012 . Fifty underwent ACL reconstruction with the QT and 45 with the HT . The same surgical technique , fixation method , and postoperative protocol were used in both groups . The following parameters were evaluated : surgical revisions , functional outcome ( Lysholm , Knee injury and Osteoarthritis Outcome Score [ KOOS ] , Tegner , subjective International Knee Documentation Committee ) , joint stability ( KT-1000 , Lachman , pivot shift ) , anterior knee pain ( Shelbourne-Trumper score ) , and isokinetic strength . Descriptive statistics are presented for these variables using the Student t test . Results : Eighty-six patients ( 45 QT , 41 HT ) were review ed with a mean follow-up of 3.6 ± 0.4 years ; minimum follow-up was 3 years . There were 4 reoperations in the QT group ( including 1 ACL revision ) and 3 in the HT group ( including 2 ACL revisions ) ( P > .05 ) . The Lysholm ( 89 ± 6.9 vs 83.1 ± 5.3 ) , KOOS Symptoms ( 90 ± 11.2 vs 81 ± 10.3 ) , and KOOS Sport ( 82 ± 11.3 vs 67 ± 12.4 ) scores were significantly better in the QT group than in the HT group . In terms of stability , the mean side-to-side difference was 1.1 ± 0.9 mm for the QT group and 3.1 ± 1.3 mm for the HT group based on KT-1000 measurements ( P The negative Lachman component was higher in the QT group than in the HT group ( 90 % vs 46 % , P the negative pivot-shift component to be higher in the QT group than in the HT group ( 90 % vs 64 % , P = .052 ) . The Shelbourne-Trumper score was the same in both groups . There was no difference between groups in terms of isokinetic strength . Conclusion : The use of a QT graft in ACL reconstruction leads to equal or better functional outcomes than does the use of an HT graft , without affecting morbidity", "PURPOSE To analyze the long-term evaluation of clinical , functional , and magnetic resonance imaging ( MRI ) results after implant-free press-fit anterior cruciate ligament ( ACL ) reconstruction with bone-patella tendon ( BPT ) versus quadrupled hamstring tendon ( HT ) grafts . METHODS Sixty-two ACL-insufficient patients were included in a prospect i ve , r and omized study ( 31 BPT and 31 HT ) . Both surgical procedures were performed without any implants by a press-fit technique by the senior author . The femoral tunnel was drilled through the anteromedial portal for anatomic placement . At 8.8 years after reconstruction , 53 patients ( 28 BPT and 25 HT ) were examined by different clinical and functional tests . Bilateral MRI scans were performed and interpreted by an independent radiologist . RESULTS On follow-up , the score on the International Knee Documentation Committee evaluation form was significantly better in the HT group . The clinical examination including range of motion , KT-1000 test ( MEDmetric , San Diego , CA ) , and pivot-shift test showed no significant differences . On isokinetic testing , the mean quadriceps strength was close to normal ( 96 % ) in both groups , but the hamstring strength was lower in the HT group ( 100.3%/95.1 % ) . Kneeling ( 1.5/1.1 , P = .002 ) , knee walking ( 1.72/1.14 , P = .002 ) , and single-leg hop test ( 95.8%/99.1 % , P = .057 ) were better in the HT group . The MRI findings about the mean degree of cartilage lesion ( International Cartilage Repair Society protocol ) of the operated ( 2.1/2.1 ) and nonoperated ( 1.4/1.8 ) knee showed no significant differences . No significant difference was found in the grade of medial or lateral meniscal lesion or the number of patients having meniscal lesions when the operated and nonoperated knees were compared . Tunnel measurements , Caton-Deschamps Index , and the sagittal ACL angle were similar . CONCLUSIONS The implant-free press-fit technique for anterior cruciate ligament reconstruction by use of bone-patellar tendon and hamstring grafts with anatomic graft placement is an innovative technique to preserve the cartilage and meniscal status without significant differences between the operated and nonoperated knees in the long term . Significantly less anterior knee pain was noted in the hamstring group , when testing for kneeling and knee walking . LEVEL OF EVIDENCE Level II , prospect i ve comparative study", "Background Patellar and hamstring tendon autografts are the most frequently used graft types for anterior cruciate ligament reconstruction , but few direct comparisons of outcomes have been published . Hypothesis There is no difference in outcome between the two types of reconstruction . Study Design Prospect i ve r and omized clinical trial . Methods After isolated anterior cruciate ligament rupture , 65 patients were r and omized to receive either a patellar tendon or a four-str and hamstring tendon graft reconstruction , and results were review ed at 4 , 8 , 12 , 24 , and 36 months . Results Pain on kneeling was more common and extension deficits were greater in the patellar tendon group . There were greater quadriceps peak torque deficits in the patellar tendon group at 4 and 8 months but not thereafter . In the hamstring tendon group , active flexion deficits were greater from 8 to 24 months , and KT-1000 arthrometer side-to-side differences in anterior knee laxity at 134 N were greater . Cincinnati knee scores , International Knee Documentation Committee ratings , and rates of return to preinjury activity levels were not significantly different between the two groups . Conclusions Both grafts result ed in satisfactory functional outcomes but with increased morbidity in the patellar tendon group and increased knee laxity and radiographic femoral tunnel widening in the hamstring tendon group", "PURPOSE The purpose of this r and omized controlled study was to compare knee stability , kneeling pain , harvest site pain , sensitivity loss , and subjective clinical outcome after primary anterior cruciate ligament ( ACL ) reconstruction with either bone-patellar tendon-bone ( BPTB ) or quadriceps tendon-bone ( QTB ) autografts in a noninferiority study design . METHODS From 2005 to 2009 , a total of 51 patients were included in the present study . Inclusion criteria were isolated ACL injuries in adults . Twenty-five patients were r and omized to BPTB grafts and 26 to QTB grafts . An independent examiner performed follow-up evaluations 1 and 2 years postoperatively . Anteroposterior knee laxity was measured with a KT-1000 arthrometer ( MEDmetric , San Diego , CA ) . Anterior knee pain was assessed clinical ly and by knee-walking ability . Knee Injury and Osteoarthritis Outcome Score ( KOOS ) and subjective International Knee Documentation Committee ( IKDC ) score were used for patient-evaluated outcome . RESULTS Anterior knee laxity was equal between the 2 groups with KT-1000 values of 1.1 ± 1.4 mm and 0.8 ± 1.7 mm st and ard deviation ( SD ) at follow-up in QTB and BPTB groups , respectively ( P = .65 ) , whereas positive pivot shift test results were seen less frequently ( 14 % compared with 38 % , respectively ; P = .03 ) . Anterior kneeling pain , evaluated by the knee walking ability test , was significantly less in the QTB group , with only 7 % of patients grading knee walking as difficult or impossible compared with 34 % in the BPTB group . At 1 and 2 years ' follow-up , there was no difference between the 2 groups in subjective patient-evaluated outcome . The IKDC score was 75 ± 13 patients and 76 ± 16 SD at 1-year follow-up in QTB and BPTB groups , respectively ( P = .78 ) . At 2 years , 12 patients were lost to follow-up , result ing in 18 in the BPTB group and 21 in the QTB group . CONCLUSIONS The use of the QTB graft results in less kneeling pain , graft site pain , and sensitivity loss than seen with BPTB grafts ; however , similar anterior knee stability and subjective outcomes are seen . The results of this study show that QTB is a viable option for ACL reconstruction . LEVEL OF EVIDENCE Level II , r and omized controlled clinical trial", "OBJECTIVE To evaluate whether increased laxity of the knee during daily physical activities such as stair climbing is associated with progression of knee joint osteoarthritis ( OA ) . METHODS During the years 2001 - 2003 , 136 patients with bilateral primary medial compartment knee joint OA were enrolled in this prospect i ve study . Baseline data collected were body mass index ( BMI ) , muscle power , radiographic joint space width , mechanical axis on st and ing radiography , and anteroposterior ( AP ) knee laxity before and after physical exercise . After 8 years of followup , 84 patients were reexamined to assess radiographic changes . Radiographic disease progression was defined as progression of > 1 grade on the Kellgren/Lawrence scale . RESULTS AP knee laxity increased significantly after stair climbing . Patients with OA progression and those without progression did not differ significantly in age , sex , baseline quadriceps muscle strength , mechanical axis , joint space width , and AP knee laxity before exercise . The 2 groups of patients did , however , differ significantly in baseline BMI and change in AP knee laxity due to exercise . The risk of progression of knee OA increased 4.15-fold with each millimeter of increase in the change in AP knee laxity due to exercise and 1.24-fold with each point increase in the BMI . CONCLUSION Our results indicate that patients with OA progression have significantly greater changes in knee joint laxity during physical activities and a higher BMI than patients without OA progression . These findings suggest that larger changes in knee laxity during repetitive physical activities and a higher BMI play significant roles in the progression of knee OA", "Background Controversy remains over the most appropriate graft for anterior cruciate ligament reconstruction . Hypothesis There is no significant difference in outcomes after 4-str and hamstring and patellar tendon autograft anterior cruciate ligament reconstructions using similar fixation techniques . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Between August 2000 and May 2003 , 64 Keller Army Hospital patients with complete anterior cruciate ligament tears were r and omized to hamstring ( n = 32 ) or patellar tendon ( n = 32 ) autograft anterior cruciate ligament reconstruction . Operative graft fixation and rehabilitative techniques were the same for both groups . Follow-up assessment s included the Single Assessment Numeric Evaluation score , Lysholm score , International Knee Documentation Committee score , and Knee Injury and Osteoarthritis Outcome Score . Postoperative radiographs were analyzed for tunnel location and orientation . Results Eleven women and 53 men were r and omized . Eighty-three percent of the patients ( 53 of 64 ) had follow-up of greater than 2 years , or to the point of graft rupture or removal ( average follow-up , 36 months ) . Four hamstring grafts ( 12.5 % ) and three patellar tendon grafts ( 9.4 % ) ( P = .71 ) ruptured . One deep infection in a hamstring graft patient necessitated graft removal . Forty-five of the 56 patients with intact grafts had greater than 2-year follow-up . Patients with patellar tendon grafts had greater Tegner activity scores ( P = .04 ) . Single Assessment Numeric Evaluation scores were 88.5 ( 95 % confidence interval : 83.1 , 93.8 ) and 90.1 ( 95 % confidence interval : 85.2 , 96.1 ) for the hamstring and patellar tendon groups , respectively ( P = .53 ) . Lysholm scores were 90.3 ( 95 % confidence interval : 84.4 , 96.1 ) and 90.4 ( 95 % confidence interval : 84.5 , 96.3 ) for the hamstring and patellar tendon groups , respectively ( P = .97 ) . There were no significant differences in knee laxity , kneeling pain , isokinetic peak torque , International Knee Documentation Committee score , or Knee Injury and Osteoarthritis Outcome Scores . Postoperative graft rupture correlated with more horizontal tibial tunnel orientation . Conclusion Hamstring and patellar tendon autografts provide similar objective , subjective , and functional outcomes when assessed at least 2 years after anterior cruciate ligament reconstruction" ]

[ "OBJECTIVES To investigate the effects of darifenacin controlled-release ( CR ) and oxybutynin extended-release ( ER ) on cognitive function ( particularly memory ) in older subjects . METHODS Healthy subjects ( n=150 ) > /=60 years were r and omised to darifenacin , oxybutynin ER or placebo in a multicentre , double-blind , double-dummy , parallel-group , 3-week study . Doses were administered according to US labels : oxybutynin ER 10 mg once daily ( od ) , increasing to 15 mg od then 20 mg od by week 3 ; darifenacin 7.5 mg od in weeks 1 and 2 , then 15 mg od in week 3 . The primary end point was accuracy on the Name-Face Association Test ( delayed recall ) at week 3 . RESULTS Results of the Name-Face Association Test at week 3 showed no significant difference between darifenacin and placebo on delayed recall ( mean difference , -0.06 , p=0.908 ) . In contrast , oxybutynin ER result ed in memory impairment , with significantly lower scores than placebo and darifenacin ( mean differences , -1.30 , p=0.011 and -1.24 , p=0.022 , respectively ) for delayed recall on the Name-Face Association Test at week 3 . Additional tests of delayed recall indicated significant memory impairment with oxybutynin ER versus placebo at certain time points , whereas darifenacin was similar to placebo . No between-treatment differences were detected in self-rated memory , demonstrating that subjects were unaware of memory deterioration . CONCLUSIONS While darifenacin had no significant effects on memory versus placebo , oxybutynin ER caused significant memory deterioration ( magnitude of effect comparable to brain aging of 10 years ) . The results also demonstrate that subjects may not recognise/report memory deterioration", "INTRODUCTION Anti-cholinergic medications have been associated with increased risks of cognitive impairment , premature mortality and increased risk of hospitalisation . Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer , yet little is known about associated adverse outcomes in this setting . METHODS A sub study of 112 participants in a r and omised control trial who had cancer and an Australia modified Karnofsky Performance Scale ( AKPS ) score ( AKPS ) of 60 or above , explored survival and health service utilisation ; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale ( modified version ) longitudinally to death . A st and ardised starting point for prospect ively calculating survival was an AKPS of 60 or above . RESULTS Baseline entry to the sub- study was a mean 62 + /- 81 days ( median 37 , range 1 - 588 ) days before death ( survival ) , with mean of 4.8 ( median 3 , SD 4.18 , range 1 - 24 ) study assessment s in this time period . Participants spent 22 % of time as an inpatient . There was no significant association between anti-cholinergic score and time spent as an inpatient ( adjusted for survival time ) ( p = 0.94 ) ; or survival time . DISCUSSION No association between anti-cholinergic load and survival or time spent as an inpatient was seen . Future studies need to include cognitively impaired population s where the risks of symptomatic deterioration may be more substantial", "BACKGROUND Observational studies report a relationship between anticholinergic drug scale ( ADS ) score and cognitive function . This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population . METHODS This r and omized , controlled , single-blinded trial , recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway . The participants were r and omly allocated ( 1:1 ) to intervention or control . The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug review s. Primary end point was Consortium to Establish a Registry for Alzheimer 's Disease 10-wordlist test for immediate recall . Secondary end points were Mini-Mental Sate Examination , delayed recall and recognition of words , saliva flow , and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks , and the study groups were compared after adjusting for baseline differences . RESULTS Eighty-seven patients were included . The median ADS score was reduced by 2 units ( p immediate recall was 0.54 words between the intervention and control group ( 95 % confidence interval [ CI ] : -0.91 , 2.05 ; p = .48 ) . The study groups did not differ significantly in any of the other cognitive end points , salvia flow , or SAA at either follow-up ( p > .18 ) . CONCLUSION Pharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function in nursing home residents . Moreover , the drug changes did not reduce SAA or mouth dryness significantly , which might indicate limited applicability of the ADS score to prevent prescription risks in this population", "PURPOSE Overactive bladder is common in the elderly population , which is susceptible to cognitive disorders and drug induced cognitive impairment . Existing overactive bladder treatments may cause adverse events , such as cognitive impairment , due to antagonism of the M1 receptor in the central nervous system . In this study we evaluated the effect of darifenacin , an M3 selective antagonist , on cognitive function in elderly volunteers without clinical dementia . MATERIAL S AND METHODS This double-blind , 3-period crossover study r and omized 129 volunteers 65 years or older with no/mild cognitive impairment to receive 3 of 5 treatments , namely darifenacin controlled release ( 3.75 , 7.5 or 15 mg once daily ) , darifenacin immediate-release ( 5 mg 3 times daily ) or matching placebo for 14 days . Each treatment period was separated by 7 days of washout . Cognitive function tests were completed at baseline and at treatment end . RESULTS For the primary end points of memory scanning sensitivity , speed of choice reaction time and word recognition sensitivity , there were no statistically significant differences for darifenacin vs placebo . There were no statistically significant differences in secondary variables except memory scanning speed , which increased in all groups relative to baseline , but improvement was greater with placebo than with 3.75 mg darifenacin . Darifenacin treatment was not associated with changes in alertness , contentment or calmness , which are likely to be clinical ly relevant . Darifenacin was well tolerated . CONCLUSIONS : In elderly volunteers 2 weeks of treatment with darifenacin had no effect on cognitive function compared with baseline and it was not significantly different from placebo . This may be related to its M3 receptor selectivity with negligible M1 receptor antagonism", "Abstract Objective To assess the potential of anticholinergic drugs as a cause of non-degenerative mild cognitive impairment in elderly people . Design Longitudinal cohort study . Setting 63 r and omly selected general practice s in the Montpellier region of southern France . Participants 372 people aged > 60 years without dementia at recruitment . Main outcome measures Anticholinergic burden from drug use , cognitive examination , and neurological assessment . Results 9.2 % of subjects continuously used anticholinergic drugs during the year before cognitive assessment . Compared with non-users , they had poorer performance on reaction time , attention , delayed non-verbal memory , narrative recall , visuospatial construction , and language tasks but not on tasks of reasoning , immediate and delayed recall of wordlists , and implicit memory . Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35 % of non-users , and anticholinergic drug use was a strong predictor of mild cognitive impairment ( odds ratio 5.12 , P = 0.001 ) . No difference was found between users and non-users in risk of developing dementia at follow-up after eight years . Conclusions Elderly people taking anticholinergic drugs had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired , although not at increased risk for dementia . Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors", "OBJECTIVES To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men . DESIGN Prospect i ve cohort study . SETTING A Department of Veterans Affairs primary care clinic . PARTICIPANTS Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension . MEASUREMENTS The outcomes were measured using the Hopkins Verbal Recall Test ( HVRT ) for short-term memory and the instrumental activity of daily living ( IADL ) scale for executive function at baseline and during follow-up . Anticholinergic medication use was ascertained using participants ' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anticholinergic score . RESULTS Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs . On average , a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point ( 95 % confidence interval (CI)= 0.05 - 0.58 ) and 0.10-point ( 95 % CI=0.04 - 0.17 ) decrease in the HVRT and IADLs , respectively , independent of other potential risk factors for cognitive impairment , including age , education , cognitive and physical function , comorbidities , and severity of hypertension . The association was attenuated but remained statistically significant with memory ( 0.29 , 95 % CI=0.01 - 0.56 ) and executive function ( 0.08 , 95 % CI=0.02 - 0.15 ) after further adjustment for concomitant non-anticholinergic medications . CONCLUSION Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men . Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects", "The pathogenesis of delirium in acute stroke is incompletely understood . The use of medications with anticholinergic ( ACH ) activity is associated with an increased frequency of delirium . We hypothesized that the intake of medications with ACH activity is associated with delirium in acute stroke patients . Delirium was assessed using the DSM‐IV‐TR criteria and the Delirium Rating Scale , in a sample of consecutive patients with an acute ( ≤4 days ) cerebral infa rct or intracerebral haemorrhage ( ICH ) . We performed a gender and age matched case – control study . Twenty‐two delirious stroke patients ( cases ) and 52 non‐delirious patients ( controls ) were compared concerning the intake of ACH medications ( i ) before stroke , ( ii ) during hospitalization but before the assessment . The variables associated with delirium on bivariate analysis were entered in a stepwise logistic regression analysis . The final regression model ( Nagelkerke R2 = 0.65 ) retained non‐neuroleptics ACH medication during hospitalization ( OR = 24.4 ; 95 % CI = 2.18–250 ) , medical complications ( OR = 20.8 ; 95 % CI = 3.46–125 ) , ACH medication taken before stroke ( OR = 17.5 ; 95 % CI = 1.00–333.3 ) and ICH ( OR = 16.9 ; 95 % CI = 2.73–100 ) as independent predictors of delirium . This preliminary result indicates that drugs with subtle ACH activity play a role in the pathogeneses of delirium in acute stroke . Medication with ACH activity should be avoided in acute stroke patients", "BACKGROUND The use of drugs with anticholinergic adverse effects is often deemed inappropriate in elderly ( aged > or = 65 years ) patients , yet studies continue to show extensive use in this population at high risk for adverse drug events ( ADEs ) . The burden of drug-related anticholinergic symptoms in community-dwelling elderly patients has not been well described . OBJECTIVE The aim of this study was to assess the prevalence of anticholinergic symptoms , corresponding symptom burden , and anticholinergic-related ADEs in a sample of community-dwelling elderly veterans . METHODS This prospect i ve cohort study was conducted at the primary care clinics at the Veterans Affairs Medical Center ( VAMC ) , Iowa City , Iowa . The study sample included r and omly selected patients with intact cognitive function attending the VAMC and prescribed > or = 5 scheduled medications . Data on current prescription and nonprescription drug use were elicited by a trained research assistant and a clinical pharmacist from patient interviews and electronic medical records . The prevalence and severity of 7 anticholinergic symptoms ( dry mouth , constipation , blurred vision , confusion , urinary hesitation , dry eyes , and drowsiness ) were assessed at baseline . The occurrence of ADEs at 12 weeks was compared between patients using anticholinergic drugs and those not using them . RESULTS A total of 532 patients were included ( 97.9 % men ; mean age , 74.3 years ; 27.1 % used at least 1 anticholinergic drug ) . Twenty-two anticholinergic drugs ( 16 prescription medications , 6 over-the-counter medications ) were identified . The mean number of anticholinergic symptoms was significantly higher in the group using anticholinergic drugs ( 3.1 vs 2.5 ; P anticholinergic drugs : dry mouth ( 57.6 % vs 45.6 % ) and constipation ( 42.4 % vs 29.4 % ) ( both , P anticholinergic drugs reported an ADE considered related to an anticholinergic drug . CONCLUSIONS Anticholinergic drug use was common ( 27.1 % ) in these elderly veterans with intact cognitive function . The mean number of anticholinergic symptoms was significantly greater in this group , and the prevalences of dry mouth and constipation were significantly higher in the group using anticholinergic drugs ( all , P Anticholinergic-related ADEs were rare ( 0.8 % ) . Although anticholinergic drugs should generally be avoided in the elderly , individual risks and benefits for a patient should be considered", "Background Drugs with anticholinergic effects are associated with adverse events such as delirium and falls as well as cognitive decline and loss of independence . Objective The aim of the study was to evaluate the association between anticholinergic burden and both cognitive and functional status , according to the hypothesis that the cumulative anticholinergic burden , as measured by the Anticholinergic Cognitive Burden ( ACB ) Scale and Anticholinergic Risk Scale ( ARS ) , increases the risk of cognitive decline and impairs activities of daily living . Methods This cross-sectional , prospect i ve study ( 3-month telephone follow-up ) was conducted in 66 Italian internal medicine and geriatric wards participating in the Registry of Polytherapies SIMI ( Società Italiana di Medicina Interna ) ( REPOSI ) study during 2010 . The sample included 1,380 in patients aged 65 years or older . Cognitive status was rated with the Short Blessed Test ( SBT ) and physical function with the Barthel Index . Each patient ’s anticholinergic burden was evaluated using the ACB and ARS scores . Results The mean SBT score for patients treated with anticholinergic drugs was higher than that for patients receiving no anticholinergic medications as also indicated by the ACB scale , even after adjustment for age , sex , education , stroke and transient ischaemic attack [ 9.2 ( 95 % CI 8.6–9.9 ) vs. 8.5 ( 95 % CI 7.8–9.2 ) ; p = 0.05 ] . There was a dose – response relationship between total ACB score and cognitive impairment . Patients identified by the ARS had more severe cognitive and physical impairment than patients identified by the ACB scale , and the dose – response relationship between this score and ability to perform activities of daily living was clear . No correlation was found with length of hospital stay . Conclusions Drugs with anticholinergic properties identified by the ACB scale and ARS are associated with worse cognitive and functional performance in elderly patients . The ACB scale might permit a rapid identification of drugs potentially associated with cognitive impairment in a dose – response pattern , but the ARS is better at rating activities of daily living", "Abstract Background : Many potentially inappropriate drugs prescribed to older people have anticholinergic properties as adverse effects and are therefore potentially harmful . These effects typically include constipation , dry mouth , blurred vision , dizziness and slowing of urination . It has been shown that drugs with anticholinergic properties ( DAPs ) are associated with cognitive decline and dementia , may contribute to events such as falls , delirium and impulsive behaviour , are associated with self-reported adverse effects and physical impairment , and may even be associated with mortality . However , studies of the prognostic implication s of DAPs remain scarce . Objective : To evaluate the impact of DAPs on hospitalization and mortality in older patients with stable cardiovascular disease ( CVD ) . Methods : This was a prospect i ve study with a mean follow-up of 3.3 years involving two study groups : users ( n = 295 ) and non-users ( n = 105 ) of DAPs . The participants were 400 community-dwelling older people ( aged 75–90 years ) with stable CVD participating in a secondary prevention study of CVD ( DEBATE ) in Helsinki , Finl and . The use of DAPs was estimated using definitions from the previous scientific literature . The Charlson Comorbidity Index ( CCI ) was used to estimate the burden of co-morbidity and the Mini-Mental State Examination test was used to assess cognitive function . The risks in the two study groups for hospital visits , number of days spent in hospital care and mortality were measured from 2000 to the end of 2003 . Results : The unadjusted follow-up mortality was 20.7 % and 9.5 % among the users and non-users of DAPs , respectively ( p = 0.010 ) . However , the use of DAPs was not a significant predictor of mortality in multivariate analysis after adjustment for age , sex and CCI score ( hazard ratio 1.57 ; 95 % CI 0.78 , 3.15 ) . The mean ± SD number of hospital days per person-year was higher in the DAP user group ( 14.9± 32.5 ) than in the non-user group ( 5.2± 12.3 ) [ p of DAPs predicted the number of days spent in hospital ( p = 0.011 ) . Conclusions : The use of DAPs in older patients with stable CVD was associated with an increased number of hospital days but not with mortality", "OBJECTIVES To examine whether anticholinergic medications have effects on the level of cognitive function or cognitive decline in persons in their early to mid 60s . METHODS A r and omly selected community-based sample of 2058 persons aged 60 - 64 at baseline was interviewed twice over four years . Anticholinergic medication use was determined from self-report medication data using the Anticholinergic Drug Scale . Cognition was assessed with the California Verbal Learning Test I ( one trial ) , Digits Backwards , the Symbol Digit Modalities Test , the Mini-Mental State Exam and simple and choice reaction time . Persons meeting criteria for Mild Cognitive Impairment were identified in a clinical sub study . Mixed models adjusting for age , sex , self-rated depression and physical health , and total number of medications were used to analyse the data . RESULTS There was a significant main effect of anticholinergic group averaged across time for the Symbol Digits Modalities Test with poorer performance among anticholinergic medication users . Main effects for the other cognitive tests and mild cognitive impairment were non-significant . No time by anticholinergic group interactions were significant . CONCLUSIONS This study suggests that exposure to anticholinergic medication is associated with lower level of complex attention in the young-old , but not with greater cognitive decline over time . Although the clinical significance of this is not clear , caution should be taken when prescribing medications with anticholinergic effects to older persons", "Objectives : To assess the cognitive effects of single doses of solifenacin 10 mg compared with placebo ( primary objective ) and oxybutynin immediate release ( IR ) 10 mg ( secondary objective ) in elderly subjects . Methods : Single-centre , r and omised , double-blind , placebo-controlled study in 12 healthy elderly volunteers , with three crossover periods separated by two 14-day washout periods . Each sequence consisted of a single dose of solifenacin 10 mg in one period , oxybutynin IR 10 mg in another and placebo in another . Aspects of attention , information processing , working memory , episodic memory and self-rated mood and alertness were tested using the vali date d Cognitive Drug Research computerised assessment system . Results : There was no evidence from absolute mean values or changes from baseline to suggest that solifenacin 10 mg impaired cognition or self-ratings of mood and alertness versus placebo . Post-hoc ANCOVA showed no statistically significant cognitive deterioration with solifenacin versus placebo , when measured at a time point closest to the probable Cmax of solifenacin . Oxybutynin was associated with statistically significant impairments in several measures of cognitive function at a time point corresponding with its probable Cmax . Conclusion : In this pilot study , single 10 mg doses of solifenacin did not show any clear propensity to impair cognitive function in a healthy elderly population", "OBJECTIVES To evaluate the association between the Drug Burden Index ( DBI ) , a measure of a person 's total exposure to anticholinergic and sedative medications that includes principles of dose-response and maximal effect and is associated with impaired physical function in community-dwelling older people , and falls in residents of residential aged care facilities ( RACFs ) . DESIGN Data were drawn from participants in a r and omized controlled trial that investigated falls and fractures . SETTING RACFs in Sydney , Australia . PARTICIPANTS Study participants ( N=602 ; 70.9 % female ) were recruited from 51 RACFs . Mean age was 85.7 ± 6.4 , and mean DBI was 0.60 ± 0.66 . MEASUREMENTS Medication history was obtained on each participant . Drugs were classified as anticholinergic or sedative and a DBI was calculated . Falls were measured over a 12-month period . Comorbidity , cognitive impairment ( Mini-Mental State Examination ) and depression ( Geriatric Depression Scale ) were determined . RESULTS There were 998 falls in 330 individuals during a follow-up period of 574.2 person-years , equating to an average rate of 1.74 falls per person-year . The univariate negative binomial regression model for falls showed incidence rate ratios of 1.69 ( 95 % confidence interval (CI)=1.22 - 2.34 ) for low DBI ( age , sex , history of falling , cognitive impairment , depression , use of a walking aid , comorbidities , polypharmacy , and incontinence , incident rate ratios of 1.61 ( 95 % CI=1.17 - 2.23 ) for low DBI and 1.90 ( 95 % CI=1.30 - 2.78 ) for high DBI were obtained . CONCLUSION DBI is significantly and independently associated with falls in older people living in RACFs . Interventional studies design ed for this population are needed to determine whether reducing DBI , through dose reduction or cessation of anticholinergic and sedative drugs , can prevent falls ", "Objective The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a r and omized , double-blind trial . Method Three hundred and seventy-seven patients were r and omly assigned to receive 2–6 mg/day of risperidone or 5–20 mg/day of olanzapine for 8 weeks . Cognitive function was assessed with a focused cognitive assessment battery ; in addition , extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale ( ESRS ) , and the positive and negative syndrome scale ( PANSS ) was rated for all patients . Results Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test , the trail-making test , the California verbal learning test , the continuous performance test , and some aspects of verbal fluency and spatial working memory . No differences in the effects of the drugs on any of the cognitive tests were noted . Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects . Conclusions Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning . Previous reports of greater benefits of olanzapine over risperidone in a small- sample pilot study were not substantiated . These results are not due in general to changes in clinical symptoms or movement disorders , suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia", "OBJECTIVES To describe the association between anticholinergic medications and incident delirium in hospitalized older adults with cognitive impairment and to test the hypothesis that anticholinergic medications would increase the risk of incident delirium . DESIGN Observational cohort study . SETTING Urban public hospital in Indianapolis , Indiana . PARTICIPANTS One hundred forty-seven participants aged 65 and older with cognitive impairment who screened negative for delirium at the time of admission to a general medical ward . MEASUREMENTS Cognitive function at the time of admission was assessed using the Short Portable Mental Status Question naire ( SPMSQ ) . Anticholinergic medication orders between the time of admission and the final delirium assessment were evaluated . Anticholinergic medication orders were identified using the Anticholinergic Cognitive Burden Scale . Delirium was assessed using the Confusion Assessment Method . RESULTS Fifty-seven percent of the cohort received at least one order for possible anticholinergic medications , and 28 % received at least one order for definite anticholinergic medications . The incident rate for delirium was 22 % of the entire cohort . After adjusting for age , sex , race , baseline SPMSQ score , and Charlson Comorbidity Index , the odds ratio ( OR ) for developing delirium in those with orders for possible anticholinergic medications was 0.33 ( 95 % confidence interval ( CI ) = 0.10 - 1.03 ) . The OR for developing delirium among those with orders for definite anticholinergic medications was 0.43 ( 95 % CI = 0.11 - 1.63 ) . CONCLUSION The results did not support the hypothesis that prescription of anticholinergic medications increases the risk of incident delirium in hospitalized older adults with cognitive impairment . This relationship needs to be established using prospect i ve study design s with medication dispensing data to improve the performance of predictive models of delirium" ]

[ "We have recently demonstrated that glucocorticoid ( GC ) suppresses bone formation and enhances bone resorption , with result ant bone loss . This altered bone turnover is not due to the action of parathyroid hormone ( PTH ) , but appears to be related to the suppression of osteoprotegerin ( OPG ) . As vitamin K2 ( menatetrenone ) has been used for the treatment of osteoporosis , the present study was carried out to evaluate the effect of vitamin K2 on GC-induced bone loss . Twenty patients with chronic glomerulonephritis treated with GC for the first time were chosen for this study . Ten patients received GC alone ( group A ) and the other 10 patients each received 15 mg of vitamin K2 per day in addition to GC ( group B ) . Markers of bone metabolism , including serum OPG , osteocalcin ( OC ) , bone-specific alkaline phosphatase activity ( BAP ) , PTH , tartrate-resistant acid phosphatase ( TRAP ) , and bone mineral density ( BMD ) , were measured before and during the treatment . OPG was significantly decreased in group A ( P TRAP was markedly increased in both groups , more particularly in group A ( P PTH was decreased in group A , but was increased in group B. OC was decreased at month 1 but subsequently increased until month 12 in both groups . BAP had decreased at month 3 in group A ( P BMD of the lumbar spine was significantly reduced after 6 months ( P GC may , at least in part , play a role in the prevention and treatment of GC-induced bone loss", "BACKGROUND Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures", "It has been previously shown that the level of circulating undercarboxylated osteocalcin ( ucOC ) is elevated in elderly women in comparison with young , healthy , premenopausal ones . To underst and the mechanism of the increase in the ucOC in the elderly and to assess its potential consequences on bone fragility , we have measured ucOC in the sera of 195 elderly institutionalized women 70 - 101 yr of age . In 45 women ( 23 % ) serum ucOC was above the upper limit of the normal range for young women . The level of ucOC was negatively correlated with 25OHD ( r = -0.32 , P hip fracture and their baseline ucOC level was higher ( P serum calcium , phosphate , alkaline phosphatase , creatinine , PTH , 250HD , and total and carboxylated OC . The risk of hip fracture was increased in women with elevated ucOC ( relative ratio 5.9 , 99.9 % Cl 1.5 - 22.7 , P calcium/vitamin D2 treatment , ucOC decreased ( P ucOC in the elderly reflects not only some degree of vitamin K deficiency but also their poor vitamin D status , suggesting that vitamin D may be important , either directly or indirectly through its effect on bone turnover , for achieving a normal gamma-carboxylation of OC . The ucOC , but not conventional calcium metabolism parameters , predicts the subsequent risk of hip fracture , suggesting that serum ucOC reflects some changes in bone matrix associated with increased fragility", "BACKGROUND Vitamin K mediates the gamma-carboxylation of glutamyl residues on several bone proteins , notably osteocalcin . High serum concentrations of undercarboxylated osteocalcin and low serum concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture . However , data are limited on the effects of dietary vitamin K. OBJECTIVE We investigated the hypothesis that high intakes of vitamin K are associated with a lower risk of hip fracture in women . DESIGN We conducted a prospect i ve analysis within the Nurses ' Health Study cohort . Diet was assessed in 72327 women aged 38 - 63 y with a food-frequency question naire in 1984 ( baseline ) . During the subsequent 10 y of follow-up , 270 hip fractures result ing from low or moderate trauma were reported . RESULTS Women in quintiles 2 - 5 of vitamin K intake had a significantly lower age-adjusted relative risk ( RR : 0.70 ; 95 % CI : 0.53 , 0.93 ) of hip fracture than women in the lowest quintile ( Risk of hip fracture was also inversely associated with lettuce consumption ( RR : 0.55 ; 95 % CI : 0.40 , 0.78 ) for one or more servings per day compared with one or fewer servings per week ) , the food that contributed the most to dietary vitamin K intakes . CONCLUSIONS Low intakes of vitamin K may increase the risk of hip fracture in women . The data support the suggestion for a re assessment of the vitamin K requirements that are based on bone health and blood coagulation", "BACKGROUND Vitamin K has been suggested to have a role in bone metabolism , and low vitamin K intake has been related to low bone density and increased risk of osteoporotic fracture . OBJECTIVE The objective of this study was to determine whether phylloquinone ( vitamin K(1 ) ) intake and biochemical indicators of vitamin K status are related to bone mineral content ( BMC ) and markers of bone formation and bone resorption in girls . DESIGN Vitamin K status [ plasma phylloquinone concentration and percentage of undercarboxylated osteocalcin ( % ucOC ) ] was measured at baseline in a study of 245 healthy girls aged 3 - 16 y. Cross-linked N-telopeptide of type 1 collagen ( NTx ) breakdown , osteocalcin , and bone-specific alkaline phosphatase were measured to reflect bone resorption and formation . BMC of the total body , lumbar spine , and hip and dietary phylloquinone intake were measured annually for 4 y. RESULTS Phylloquinone intake ( median : 45 microg/d ) was not consistently associated with bone turnover markers or BMC . Better vitamin K status ( high plasma phylloquinone and low % ucOC ) was associated with lower bone resorption and formation . Plasma phylloquinone was inversely associated with NTx and osteocalcin concentrations ( P ucOC was positively associated with NTx and bone-specific alkaline phosphatase concentrations ( P BMC or gain in BMC over the 4-y study period . CONCLUSIONS Better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical US diet . R and omized phylloquinone supplementation trials are needed to further underst and the potential benefits of phylloquinone on bone acquisition in growing children", "Background : Low bone mass leading to stress fractures is a well-known and yet unsolved problem among female athletes . Purpose : To quantify the rate of bone loss in healthy female athletes and investigate the effects of estrogen and vitamin K supplementation on bone loss . Study Design : Prospect i ve cohort study . Methods : We classified 115 female endurance athletes into amenorrheic , eumenorrheic , or estrogen-supplemented groups and r and omized them to receive either placebo or vitamin K1 . The bone mineral densities of the subjects ' femoral neck and lumbar spine were measured at baseline and after 2 years . Results : Bone mineral density in the lumbar spine remained constant , but bone density in the femoral neck had decreased significantly after 2 years in all three subgroups . The decrease was higher in amenorrheic ( —6.5 % ± 4.0 % ) than in eumenorrheic ( —3.2 % ± 4.1 % ) and estrogen-supplemented athletes ( —3.9 % ± 3.1 % ) . Supplementation with vitamin K did not affect the rate of bone loss . Conclusions : The rate of bone loss in all three subgroups of female athletes was unexpectedly high ; neither estrogen nor vitamin K supplementation prevented bone loss . Clinical Relevance : High-intensity training maintained over several years must be regarded in women as a risk factor for osteoporosis , and protocol s for optimal treatment should be developed", "The effect of maternal phylloquinone supplementation on vitamin K in breast milk was studied to establish : ( 1 ) if phylloquinone is the source of menaquinone-4 in breast milk ; ( 2 ) the dose-effect relationship between intake and obtainable levels . Four groups of lactating mothers with a full-term healthy infant participated and took oral phylloquinone supplements of 0.0 ( n 8) , 0.8 ( n 8) , 2.0 ( n 8) , and 4.0 ( n 7 ) mg/d for 12d , starting at day 4 post-partum . Milk sample s were collected on days 4 , 8 , 16 , and 19 . Blood sample s were collected on days 4 and 16 . Vitamin K and vitamin E concentrations , the latter for reason of comparison , were assayed . Phylloquinone and menaquinone-4 were present in all milk sample s : 5.84 ( SD 2.31 ) and 2.98 ( SD 1.51 ) nmol/l ( n 31 ) respectively , in colostrum ( day 4 sample ) . A strong correlation between the vitamers was found ( r 0.78 , P Breast-milk phylloquinone levels were raised in a dose-dependent manner : 4- , 12- , and 30-fold on day 16 for the 08 , 2.0 , and 4.0 mg group respectively . In addition , menaquinone-4 levels were higher : 2.5- ( P Plasma of supplemented subjects contained 3- , 5- , and 10-fold higher phylloquinone levels on day 16 . Detectable menaquinone-4 was found in ten of thirty-one day 4 plasma sample s. All day 16 plasma sample s of the 4 mg supplemented group contained the vitamin . There was no correlation between the K-vitamers in plasma . Vitamin E and phylloquinone appear to differ in their distribution in breast milk , milk : plasma concentration ratios were milk : plasma concentration ratio of menaquinone-4 was > 10 . In conclusion , dietary phylloquinone is a source of menaquinone-4 in breast milk . Phylloquinone supplementation to lactating mothers may be of benefit to the newborn infant , since both phylloquinone and menaquinone-4 are raised by supplementation", "BACKGROUND Previous studies have shown that alendronate can increase bone mineral density ( BMD ) and prevent radiographically defined ( morphometric ) vertebral fractures . The Fracture Intervention Trial aim ed to investigate the effect of alendronate on the risk of morphometric as well as clinical ly evident fractures in postmenopausal women with low bone mass . METHODS Women aged 55 - 81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture . Results for women with at least one vertebral fracture at baseline are reported here . 2027 women were r and omly assigned placebo ( 1005 ) or alendronate ( 1022 ) and followed up for 36 months . The dose of alendronate ( initially 5 mg daily ) was increased ( to 10 mg daily ) at 24 months , with maintenance of the double blind . Lateral spine radiography was done at baseline and at 24 and 36 months . New vertebral fractures , the primary endpoint , were defined by morphometry as a decrease of 20 % ( and at least 4 mm ) in at least one vertebral height between the baseline and latest follow-up radiograph . Non-spine clinical fractures were confirmed by radiographic reports . New symptomatic vertebral fractures were based on self-report and confirmed by radiography . FINDINGS Follow-up radiographs were obtained for 1946 women ( 98 % of surviving participants ) . 78 ( 8.0 % ) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 ( 15.0 % ) in the placebo group ( relative risk 0.53 [ 95 % Cl 0.41 - 0.68 ] ) . For clinical ly apparent vertebral fractures , the corresponding numbers were 23 ( 2.3 % ) alendronate and 50 ( 5.0 % ) placebo ( relative hazard 0.45 [ 0.27 - 0.72 ] ) . The risk of any clinical fracture , the main secondary endpoint , was lower in the alendronate than in the placebo group ( 139 [ 13.6 % ] vs 183 [ 18.2 % ] ; relative hazard 0.72 [ 0.58 - 0.90 ] ) . The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 ( 0.23 - 0.99 ) and 0.52 ( 0.31 - 0.87 ) . There was no significant difference between the groups in numbers of adverse experiences , including upper-gastrointestinal disorders . INTERPRETATION We conclude that among women with low bone mass and existing vertebral fractures , alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures , as well as other clinical fractures", "PURPOSE To assess the comparative effectiveness of several medications on bone mineral density , biochemical bone markers , and the incidence of vertebral fractures in postmenopausal women with osteoporosis . METHODS A total of 396 postmenopausal women , aged 50 to 75 years , were allocated r and omly to six equal-sized groups : hormone replacement therapy , etidronate , eel calcitonin , alfacalcidol , vitamin K ( menatetrenone ) , or control ( no treatment ) . Thoracic and lumbar spine radiographs , bone mineral density at the distal radius , and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study . RESULTS Compared with baseline , the 2-year mean changes in bone mineral density were 2.0 % for hormone replacement therapy , -0.5 % for etidronate , 1.6 % for calcitonin , -3.6 % for alfacalcidol , -1.9 % for vitamin K , and -3.3 % for control . Seventeen ( 26 % ) of the 66 control patients developed new vertebral fractures . Compared with controls , the relative risks of vertebral fracture were 0.35 ( 95 % confidence interval [ CI ] : 0.14 to 0.83 ) for hormone replacement therapy , 0.40 ( 95 % CI : 0.17 to 0.92 ) for etidronate , 0.41 ( 95 % CI : 0.17 to 0.93 ) for calcitonin , 0.56 ( 95 % CI : 0.26 to 1.12 ) for alfacalcidol , and 0.44 ( 95 % CI : 0.20 to 0.99 ) for vitamin K. CONCLUSION We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy , etidronate , and calcitonin , and significant improvements in bone mineral density with hormone replacement therapy and calcitonin", "Although several observational studies have demonstrated an association between vitamin K status and bone mineral density ( BMD ) in postmenopausal women , no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far . In the trial presented here we have investigated the potential complementary effect of vitamin K1 ( 1 mg/day ) and a mineral + vitamin D supplement ( 8 µg/day ) on postmenopausal bone loss . The design of our study was a r and omized , double-blind , placebo-controlled intervention study ; 181 healthy postmenopausal women between 50 and 60 years old were recruited , 155 of whom completed the study . During the 3-year treatment period , participants received a daily supplement containing either placebo , or calcium , magnesium , zinc , and vitamin D ( MD group ) , or the same formulation with additional vitamin K1 ( MDK group ) . The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years , as measured by DXA . The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck : after 3 years the difference between the MDK and the placebo group was 1.7 % ( 95 % Cl : 0.35–3.44 ) and that between the MDK and MD group was 1.3 % ( 95 % Cl : 0.10–3.41 ) . No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine . If co-administered with minerals and vitamin D , vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck", "Significant reduction in bone mineral density ( BMD ) occurs in patients with Parkinson 's disease ( PD ) , correlating with immobilization and with vitamin D deficiency , and increasing the risk of hip fracture , especially in elderly women . As a biological indicator of compromised vitamin K status , an increased serum concentration of undercarboxylated osteocalcin ( Oc ) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women . We evaluated treatment with vitamin K(2 ) ( menatetrenone ; MK-4 ) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD . In a r and om and prospect i ve study of PD patients , 60 received 45 mg of MK-4 daily for 12 months , and the remaining 60 ( untreated group ) did not . At baseline , patients of both groups showed vitamin D and K(1 ) deficiencies , high serum levels of ionized calcium , and glutaminic residue ( Glu ) Oc , and low levels of parathyroid hormone ( PTH ) and 1,25-dihydroxyvitamin D [ 1,25-(OH)(2)D ] , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion . BMD in the second metacarpals increased by 0.9 % in the treated group and decreased by 4.3 % in the untreated group ( p Vitamin K(2 ) level increased by 259.8 % in the treated group . Correspondingly , significant decreases in Glu Oc and calcium were observed in the treated group , in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures ( eight at the hip and two at other sites ) in the untreated group , and one hip fracture occurred among treated patients ( p = 0.0082 ; odds ratio = 11.5 ) . The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration , and it can also decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1,25-(OH)(2)D concentration", "Abstract The effect of the combined administration of vitamin D3 and vitamin K2 on bone mineral density ( BMD ) of the lumbar spine was examined in postmenopausal women with osteoporosis . Ninety-two osteoporotic women who were more than 5 years after menopause , aged 55–81 years , were r and omly divided into four administration groups : vitamin D3 ( 1α hydroxyvitamin D3 , 0.75 μg/day ) ( D group ; n = 29 ) , vitamin K2 ( menatetrenone , 45 mg/day ) ( K group ; n = 22 ) , vitamin D3 plus vitamin K2 ( DK group , n = 21 ) , and calcium ( calcium lactate , 2 g/day ) ( C group ; n = 20 ) . BMD of the lumbar spine ( L2–L4 ) was measured by dual energy X-ray absorptiometry at 0 , 1 , and 2 years after the treatment started . There were no significant differences in age , body mass index , years since menopause , and initial BMD among the four groups . One-way analysis of variance ( ANOVA ) with repeated measurements showed a significant decrease in BMD in the C group ( P increase in BMD in the D and K groups compared with that in the C group ( P in BMD in the DK group compared with that in the C , D , and K groups ( P of vitamin D3 and vitamin K2 , compared with calcium administration , appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "The purpose of this study is to evaluate the efficacy of vitamin K2 and 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2D3 ] in preventing bone loss induced by estrogen deficiency during therapy with the GnRH agonist ( GnRH-a ) leuprolide . One hundred ten women ( mean age , 46.2+/-0.5 yr ) , receiving leuprolide therapy for estrogen-dependent diseases ( such as endometriosis and uterine leiomyomas ) , were r and omly allocated into four groups ( group A , leuprolide only ; group B , leuprolide with vitamin K2 ; group C , leuprolide with 1,25-(OH)2D3 ; and group D , leuprolide with vitamin K2 and 1,25-(OH)2D3 ) . Bone mineral density of the lumbar spine was measured by dual-energy x-ray absorptiometry before and after 6 months of treatment . Bone formation and resorption markers were also measured before and after 6 months of treatment . There were no significant differences in the background parameters among the four groups . Bone mineral density was reduced in all four groups , but the percent changes varied slightly , at - 5.25 % ( group A ) , -3.72 % ( P Bone formation markers were significantly increased in all four groups , and the percent changes of bone formation markers were highest in group B. Bone resorption markers also increased significantly in all four groups after treatment of 6 months . Group B tended to have the highest percent changes of bone resorption markers among the four groups , but these increases were not significantly different between any of the groups . Vitamin K2 , especially when combined with 1,25-(OH)2D3 , can partially prevent bone loss caused by estrogen deficiency . However , because this effect is attributable mainly to the activation of bone formation , it is not sufficient to eliminate bone loss induced by GnRH-a therapy", "OBJECTIVES To investigate the effect of vitamin K2 treatment for a year on spinal bone mineral density ( BMD ) in postmenopausal women , comparing with vitamin D3 hormone replacement therapy and to determine the factors which affect the efficacy of vitamin K2 therapy . SUBJECTS AND METHODS Seventy-two postmenopausal women were r and omized into four groups and treated with respective agents . Before the therapy , 6 and 12 months after the treatment , their lumbar spine BMD were measured by dual energy X-ray absorptiometry . The rates of change in BMD ( delta BMD ) were calculated . Correlations of BMD with age , year since menopause and the initial BMD were determined . RESULTS Vitamin K2 suppressed the decrease in spinal BMD as compared with no treatment group . BMD in women treated with vitamin K2 was inversely correlated with their age ( r = -0.54 ; P Vitamin K2 therapy may be a useful method for preventing postmenopausal spinal bone mineral loss . In addition , the therapy should be started early in postmenopausal period", "BACKGROUND Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia , but their effects on fractures are unknown . METHODS We r and omly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone ( 1 - 34 ) or placebo , administered subcutaneously by the women daily . We obtained vertebral radiographs at base line and at the end of the study ( median duration of observation , 21 months ) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry . RESULTS New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent , respectively , of the women in the 20-microg and 40-microg parathyroid hormone groups ; the respective relative risks of fracture in the 20-microg and 40-microg groups , as compared with the placebo group , were 0.35 and 0.31 ( 95 percent confidence intervals , 0.22 to 0.55 and 0.19 to 0.50 ) . New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group ( relative risk , 0.47 and 0.46 , respectively [ 95 percent confidence intervals , 0.25 to 0.88 and 0.25 to 0.861 ) . As compared with placebo , the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck ; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points . Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo . Parathyroid hormone had only minor side effects ( occasional nausea and headache ) . CONCLUSIONS Treatment of postmenopausal osteoporosis with parathyroid hormone ( 1 - 34 ) decreases the risk of vertebral and nonvertebral fractures ; increases vertebral , femoral , and total-body bone mineral density ; and is well tolerated . The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects", "We attempted to investigate whether vitamin K2 ( menatetrenone ) treatment effectively prevents the incidence of new fractures in osteoporosis . A total of 241 osteoporotic patients were enrolled in a 24-month r and omized open label study . The control group ( without treatment ; n = 121 ) and the vitamin K2-treated group ( n = 120 ) , which received 45 mg/day orally vitamin K2 , were followed for lumbar bone mineral density ( LBMD ; measured by dual-energy X-ray absorptiometry [ DXA ] ) and occurrence of new clinical fractures . Serum level of Glu-osteocalcin ( Glu-OC ) and menaquinone-4 levels were measured at the end of the follow-up period . Serum level of OC and urinary excretion of deoxypyridinoline ( DPD ) were measured before and after the treatment . The background data of these two groups were identical . The incidence of clinical fractures during the 2 years of treatment in the control was higher than the vitamin K2-treated group ( chi2 = 10.935 ; p = 0.0273 ) . The percentages of change from the initial value of LBMD at 6 , 12 , and 24 months after the initiation of the study were -1.8 + /- 0.6 % , -2.4 + /- 0.7 % , and -3.3 + /- 0.8 % for the control group , and 1.4 + /- 0.7 % , -0.1 + /- 0.6 % , and -0.5 + /- 1.0 % for the vitamin K2-treated group , respectively . The changes in LBMD at each time point were significantly different between the control and the treated group ( p = 0.0010 for 6 months , p = 0.0153 for 12 months , and p = 0.0339 for 24 months ) . The serum levels of Glu-OC at the end of the observation period in the control and the treated group were 3.0 + /- 0.3 ng/ml and 1.6 + /- 0.1 ng/ml , respectively ( p serum level of OC measured by the conventional radioimmunoassay ( RIA ) showed a significant rise ( 42.4 + /-6.9 % from the basal value ) in the treated group at 24 months ( 18.2 + /- 6.1 % for the controls;p = 0.0081 ) . There was no significant change in urinary DPD excretion in the treated group . These findings suggest that vitamin K2 treatment effectively prevents the occurrence of new fractures , although the vitamin K2-treated group failed to increase in LBMD . Furthermore , vitamin K2 treatment enhances gamma-carboxylation of the OC molecule", "BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people", "Significant reduction in bone mineral density ( BMD ) occurs in stroke patients on the hemiplegic and contralateral sides , correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition , and increasing the risk of hip fracture . We evaluated the efficacy of vitamin K2 ( menatetrenone : menaquinone-4 ; MK-4 ) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients . In a r and om and prospect i ve study , of 108 hemiplegic patients following stroke , 54 received 45 mg menatetrenone daily ( MK-4 group , n = 54 ) for 12 months , and the remaining 54 ( untreatment group ) did not . Nine patients excluded from the study . The BMD in the second metacarpals and serum indices of bone metabolism were determined . BMD on the hemiplegic side increased by 4.3 % in the MK-4 group and decreased by 4.7 % in the untreated group ( p BMD on the intact side decreased by 0.9 % in the MK-4 group and by 2.7 % in the untreated group ( p both groups showed vitamin D and K1 deficiencies , high serum levels of ionized calcium , pyridinoline cross-linked carboxyterminal telopeptide of type I collagen ( ICTP ) , and low levels of parathyroid hormones ( PTH ) and bone Gla proteins ( BGP ) , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) and compensatory PTH secretion . Both vitamins K1 and K2 increased by 97.6 % and 666.9 % , respectively , in the MK-4 group . Correspondingly , a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group , in association with a simultaneous increase in both PTH and 1 , 25-[OH]2D . One patient in the untreated group suffered from a hip fracture , compared with none in the MK-4 group . The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration , and it also can decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1 , 25-[OH]2D concentration", "Abstract . The purpose of the present study was to compare the effects of etidronate and menatetrenone on bone mineral density ( BMD ) and the incidence of vertebral fractures in postmenopausal women with osteoporosis . Seventy-two osteoporotic women , more than 5 years after menopause , 53–78 years of age , were r and omly divided into three administration groups : E group ; intermittent cyclical etidronate ( 200 mg/day , 14 days per 3 months ; n = 25 ) ; M group ; menatetrenone ( 45 mg/day , daily ; n = 23 ) ; and C group ( control ) ; calcium lactate ( 2 g/day , daily ; n = 24 ) . Forearm BMD was measured by dual-energy X-ray absorptiometry at 0 , 6 , 12 , 18 , and 24 months after the treatment started . There were no significant differences in age , body mass index , years since menopause , and initial BMD among the three groups . One-way analysis of variance ( ANOVA ) with repeated measurements showed a significant decrease in BMD in the C group ( P increase in BMD in the M group compared with that in the C group ( P increase in BMD in the E group compared with that in the C and M groups ( P The indices of new vertebral fractures/1000 patient-years in the E and M groups were significantly higher than that in the C group ( χ2 = 47.7 ; P in BMD produced by me-natetrenone , this agent , as well as etidronate , may have the potential to reduce osteoporotic vertebral fractures in postmenopausal women with osteoporosis" ]

[ "To compare the use of r and omized controls ( RCTs ) and historical controls ( HCTs ) for clinical trials , we search ed the literature for therapies studied by both methods . We found six therapies for which 50 RCTs and 56 HCTs were reported . Forty-four of 56 HCTs ( 79 percent ) found the therapy better than the control regimen , but only 10 of 50 RCTs ( 20 percent ) agreed . For each therapy , the treated patients in RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups , with HCT control patients generally doing worse than the RCT control groups . Adjustment of the outcomes of the HCTs for prognostic factors , when possible , did not appreciably change the results . The data suggest that biases in patient selection may irretrievably weight the outcome of HCts in favor of new therapies . RCTs may miss clinical ly important benefits because of inadequate attention to sample size . The predictive value of each might be improved by reconsidering the use of p less than 0.05 as the significance level for all types of clinical trials , and by the use of confidence intervals around estimates of treatment effects", "A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity", "Study Design . The study was carried out as an open , r and omized , multicenter , parallel‐group study with an observation period of 12 months . Four Norwegian physiotherapy institutes took part . Patients were subsequently followed for 12 months of home exercise on their own , without the supervision of a physiotherapist . Objectives . 1 ) To investigate and compare the effects of two different exercise programs on low back problems in patients after a 1‐year training program under the supervision of a physiotherapist . 2 ) To investigate the effect supervision by , and motivation from , physiotherapists has on training compliance and efficacy . Summary of Background Data . After ordinary physiotherapy treatment for low back problems , patients were r and omly allocated either to a conventional training program design ed by physiotherapists or to a training program using a new Norwegian‐developed training apparatus called the TerapiMaster . The study included 153 patients with low back problems , all of whom had been referred to physiotherapy by their general practitioners . One hundred twenty‐six patients were followed for an additional 12 months when performing home exercise programs on their own . Methods . Monitoring patient satisfaction with the training program , compliance with the program , and absenteeism from work during the training period . Results . Patient satisfaction with both training programs was high , with about 83 % of participating patients completing the study in accordance with the protocol . Mean absenteeism ( SD ) during the preceding year totaled 82.5 days ( 19.8 ) in the conventional training group and 61.6 days ( 14.7 ) in the TerapiMaster group . Significant reductions to 17.2 days ( 6.0 ) and 15.4 days ( 5.3 ) in the two groups , respectively , were recorded during the training period , corresponding to a 75 % to 80 % reduction compared with the preceding 1‐year period . Mean absenteeism showed a further significant decline during the 12‐month period without supervised training . The average values were 9.9 days ( 3.2 ) for conventional training and 9.3 days ( 3.1 ) for the TerapiMaster , respectively . Conclusions . Both exercise programs reduced absenteeism significantly ( 75‐80 % ) . No difference in the effects of the two different programs was discernible . Regular follow‐up through encouragement and variation in the training programs appear to be important factors for motivating patients to adhere to regular exercise programs for low back problems . This thesis was corroborated by the 12‐month study of unsupervised exercise", "CONTEXT Low back pain is a frequent and costly health problem . Prevention of low back pain is important both for the individual patient and from an economic perspective . OBJECTIVE To assess the efficacy of lumbar supports and education in the prevention of low back pain in industry . DESIGN A r and omized controlled trial with a factorial design . SETTING The cargo department of an airline company in the Netherl and s. PARTICIPANTS A total of 312 workers were r and omized , of whom 282 were available for the 6-month follow-up . INTERVENTIONS Subjects were r and omly assigned to 4 groups : ( 1 ) education ( lifting instructions ) and lumbar support , ( 2 ) education , ( 3 ) lumbar support , and ( 4 ) no intervention . Education consisted of 3 group sessions on lifting techniques with a total duration of 5 hours . Lumbar supports were recommended to be used during working hours for 6 months . MAIN OUTCOME MEASURES Low back pain incidence and sick leave because of back pain during the 6-month intervention period . RESULTS Compliance with wearing the lumbar support at least half the time was 43 % . In the 282 subjects for whom data were available , no statistically significant differences in back pain incidence ( 48 [ 36 % ] of 134 with lumbar support vs 51 [ 34 % ] of 148 without , P=.81 ) or in sick leave because of low back pain ( mean , 0.4 days per month with lumbar support vs 0.4 days without , P=.52 ) were found among the intervention groups . In a subgroup of subjects with low back pain at baseline , lumbar supports reduced the number of days with low back pain per month ( median , 1.2 vs 6.5 days per month ; P=.03 ) . CONCLUSIONS Overall , lumbar supports or education did not lead to a reduction in low back pain incidence or sick leave . The results of the subgroup analysis need to be confirmed by future research . Based on our results , the use of education or lumbar supports can not be recommended in the prevention of low back pain in industry", "We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11", "The aim of the present controlled study was to evaluate the effect of a general fitness program , performed by an occupational health service , using pre-post assessment for a number of different outcome measures . A total of 160 employees working in the central home care service district of Umeå , Sweden were asked to participate in a program of a 1-year long exercise program . Of the 160 selected , 54 subjects declined to participate and nine subjects were rejected after a medical check up . The remaining 97 subjects participated in a schedule consisting of pre-post medical and physiotherapy examinations , question naires concerning sociodemography , musculoskeletal and general health complaints and work environment , physiological tests of cardiovascular fitness , and of strength and endurance of shoulder flexors and knee extensors , and registration of sick leave . The subjects were r and omly assigned to an exercise ( treatment ) or control group . The exercise group trained twice a week for 1 year using a mixed program including exercises for coordination , strength/endurance , and fitness . The test schedule was repeated for both groups after 1 year . The exercise intervention was associated with positive changes in prevalence and intensity of musculoskeletal and psychosomatic complaints , better physiotherapy status ( less muscle tightness , better neck mobility , and less tender points ) , increased shoulder strength and increased coordination in thigh muscles . However , the exercise group reported worse situations post-exercise concerning aspects of their physical and psychosocial work-environment ( i.e. , concerning ergonomy , influence , appreciation and communication with work manager ) , which might have been due to stress associated with the exercise situation", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "Back-related injuries have become a major health problem in the workplace , affecting as many as 35 percent of the work force and accounting for about 25 percent of all compensation cl aims . This study evaluates a back injury prevention program among employees in a northern California county in 1989 - 90 . Six divisions of the county government were selected for the study because they had the highest prevalence of back pain experienced and the most back-related injuries in recent years . Four of the six divisions were r and omly selected as the intervention group and the remaining two , the control group . Overall , 77 percent or 205 of the targeted employees in the intervention group participated in the study . The intervention group was given an identical health risk assessment ( HRA ) before and after the 1-year back injury prevention program that offered employees a combination of education , training , physical fitness activities , and ergonomic improvement . The control group was neither given the HRA nor offered the program . The back injury and cost data of both the control and intervention groups were collected before and after the 1-year intervention . The results showed a modest overall decline in back pain prevalence rates , but significant improvement in satisfaction and reduction in risky behaviors . Cost-benefit analysis showed the net benefit of introducing back injury prevention program was $ 161,108 , and the return on investment is 179 percent . Therefore , the study offers suggestive evidence for the initial benefits of a back injury prevention program and lends support to the widely held belief that health promotion in the workplace can reduce employee health risks , increase healthful behaviors and attitudes , and improve attitudes toward the employer organization . Whether such intervention will continue to reap benefits in future years depends , to a large extent , on a favorable work environment and the maintenance and continuation of positive behavioral changes", "This study was design ed to determine which method of instruction in body mechanics results in the higher subsequent use of the techniques taught . Two groups were formed from nursing personnel at a rural general medical-surgical hospital in the southwestern United States . Subjects from the direct care nursing staff were r and omly assigned to one of the two groups . One group attended two hours of classroom instruction in body mechanics , while the other completed an independent study module . Subjects were pre- and posttested using the Work-Related Body Mechanics Evaluation ( Carlton , 1987 ) while performing a st and ardized lifting task in the clinical setting . Using analysis of covariance , no significant differences were found in the posttest scores of the two groups", "This study was funded in part by NIH grant AR36308 The authors thank the employees of the United States Postal Service and the American Postal Workers Union ( APWU ) , Boston Metro Area Local , and Maith and lers Local 301 for their help and cooperation ; therapists from the Department of Rehabilitation Services , Bngham and Women 's Hospital for help in training workers ; and Ms Nancy Tanner for", "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", "& NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems", "This study was design ed to determine the effect of multimodal intervention and the prevention of back injury , and to evaluate the adverse side effects of using a lumbosacral corset in the workplace . Subjects were 90 male warehouse workers r and omly selected from over 800 employees at a grocery distribution center . Subjects were assigned to three groups : true controls , no back school , no brace orthoses ; back school only ; and back school plus wearing a custom molded lumbosacral orthosis . Comparisons of pre-testing and 6-month follow-up posttesting for abdominal strength , cognitive data , work injury incidence and productivity and use of health care services were evaluated . Controls and training-only group showed no changes in strength productivity or lost time . Orthoses and training-group showed no changes in strength productivity or accident rate ; however , they showed substantially less lost time . This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss . It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries", "The personnel at a geriatric hospital were r and omized into two groups . One group was allowed to exercise during working hours to improve back muscle strength , endurance , and coordination . The other group did not participate in the exercise program and received no further advice or information . After 13 months , the training group had increased back muscle strength . One subject had been absent from work 28 days in the training group whereas 12 subjects had been absent 155 days from work because of low back pain in the control group ( P back pain complaints and intensity of back pain in the training group also decreased in a statistically significant way . Every hour spent by the physiotherapist on the training group reduced the work absence among the participants by 1.3 days , result ing in a cost/benefit ratio greater than 10", "We analysed the results of 221 comparisons of an innovation with a st and ard treatment in surgery published in six leading surgery journals in 1983 to relate features of study design to the magnitude of gain . For each comparison we measured the gain attributed to the innovation over the st and ard therapy by the Mann-Whitney statistic and the difference in proportion of treatment successes . For primary treatments ( aim ed at curing or ameliorating a patient 's principal disease ) , an average gain of 0.56 was produced by 20 r and omized controlled trials . This was less than the 0.62 average for four non-r and omized controlled trials , 0.63 for 19 externally controlled trials , and 0.57 for 73 record review s ( 0.50 represents a toss-up between innovation and st and ard ) . For secondary therapies ( used to prevent or treat complications of therapy ) , the average gain was 0.53 for 61 r and omized controlled trials , 0.58 for eleven non-r and omized controlled trials , 0.54 for eight externally controlled trials , and 0.55 for 18 record review s. Readers of studies evaluating new treatments , particularly for primary treatments , may consider adjustment of the gain according to the study type", "Thirty food service workers were r and omly assigned to two groups ; one group received body mechanics instruction while the other did not . The application of the instruction was measured by evaluating the subjects ' use of body mechanics on a novel lifting and lowering task and during performance on the job . Results indicated that the group which received instruction performed significantly better on the novel task than the group that received no instruction . However , no significant difference between groups was found in performance in the work environment . The role of the occupational therapist in a work-related safety program is also discussed", "The purpose s of this study were to evaluate the effect of a weekly exercise program on short-term sick leave ( less than 50 days ) attributable to back pain and to determine whether changes in absenteeism were related to changes in cardiovascular fitness . Subjects were r and omly assigned to an exercise group ( n = 58 ) and a control group ( n = 53 ) . Sick leave attributable to back pain was determined in the intervention period of 1 1/2 years and a comparable 1 1/2-year period prior to the study . In the exercise group , the number of episodes of back pain and the number of sick-leave days attributable to back pain in the intervention period decreased by over 50 % . Absenteeism attributable to back pain increased in the control group . The decrease in sick leave in the exercise group was not accompanied by any change in cardiovascular fitness . Suggestions for establishing exercise programs are given", "Thirty young workers ( aged 14 to 19 years ) employed as groundskeepers and custodians were r and omly assigned to two groups ; one group received body mechanics instruction and the other did not . The instruction focused on proper spinal alignment in the work environment . Instruction on low back pain began with one classroom session before the subjects ' first day of work and continued during employment with two on-site sessions . The effect of instruction was evaluated through the observation of body mechanics during actual work performance . The results of the study indicate that the group that received instruction performed significantly better than the control group . This paper also discusses the occupational therapist 's role in providing job-specific body mechanics instruction in the work environment as a primary method of preventing low back pain" ]

[ "IMPORTANCE Short-term studies show that bariatric surgery causes remission of diabetes . The long-term outcomes for remission and diabetes-related complications are not known . OBJECTIVES To determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery . DESIGN , SETTING , AND PARTICIPANTS The Swedish Obese Subjects ( SOS ) is a prospect i ve matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden . Of patients recruited between September 1 , 1987 , and January 31 , 2001 , 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline . For the current analysis , diabetes status was determined at SOS health examinations until May 22 , 2013 . Information on diabetes complications was obtained from national health registers until December 31 , 2012 . Participation rates at the 2- , 10- , and 15-year examinations were 81 % , 58 % , and 41 % in the control group and 90 % , 76 % , and 47 % in the surgery group . For diabetes assessment , the median follow-up time was 10 years ( interquartile range [ IQR ] , 2 - 15 ) and 10 years ( IQR , 10 - 15 ) in the control and surgery groups , respectively . For diabetes complications , the median follow-up time was 17.6 years ( IQR , 14.2 - 19.8 ) and 18.1 years ( IQR , 15.2 - 21.1 ) in the control and surgery groups , respectively . INTERVENTIONS Adjustable or nonadjustable b and ing ( n = 61 ) , vertical b and ed gastroplasty ( n = 227 ) , or gastric bypass ( n = 55 ) procedures were performed in the surgery group , and usual obesity and diabetes care was provided to the control group . MAIN OUTCOMES AND MEASURES Diabetes remission , relapse , and diabetes complications . Remission was defined as blood glucose mg/dL and no diabetes medication . RESULTS The diabetes remission rate 2 years after surgery was 16.4 % ( 95 % CI , 11.7%-22.2 % ; 34/207 ) for control patients and 72.3 % ( 95 % CI , 66.9%-77.2 % ; 219/303 ) for bariatric surgery patients ( odds ratio [ OR ] , 13.3 ; 95 % CI , 8.5 - 20.7 ; P the diabetes remission rates decreased to 6.5 % ( 4/62 ) for control patients and to 30.4 % ( 35/115 ) for bariatric surgery patients ( OR , 6.3 ; 95 % CI , 2.1 - 18.9 ; P the cumulative incidence of microvascular complications was 41.8 per 1000 person-years ( 95 % CI , 35.3 - 49.5 ) for control patients and 20.6 per 1000 person-years ( 95 % CI , 17.0 - 24.9 ) in the surgery group ( hazard ratio [ HR ] , 0.44 ; 95 % CI , 0.34 - 0.56 ; P Macrovascular complications were observed in 44.2 per 1000 person-years ( 95 % CI , 37.5 - 52.1 ) in control patients and 31.7 per 1000 person-years ( 95 % CI , 27.0 - 37.2 ) for the surgical group ( HR , 0.68 ; 95 % CI , 0.54 - 0.85 ; P = .001 ) . CONCLUSIONS AND RELEVANCE In this very long-term follow-up observational study of obese patients with type 2 diabetes , bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care . These findings require confirmation in r and omized trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01479452", "BACKGROUND Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone . In an analysis of data from a nonr and omized , prospect i ve , controlled study , we examined the effects of bariatric surgery on the prevention of type 2 diabetes . METHODS In this analysis , we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls ( with matching performed on a group , rather than individual , level ) . None of the participants had diabetes at baseline . Patients in the bariatric-surgery cohort underwent b and ing ( 19 % ) , vertical b and ed gastroplasty ( 69 % ) , or gastric bypass ( 12 % ) ; nonr and omized , matched , prospect i ve controls received usual care . Participants were 37 to 60 years of age , and the body-mass index ( BMI ; the weight in kilograms divided by the square of the height in meters ) was 34 or more in men and 38 or more in women . This analysis focused on the rate of incident type 2 diabetes , which was a prespecified secondary end point in the main study . At the time of this analysis ( January 1 , 2012 ) , participants had been followed for up to 15 years . Despite matching , some baseline characteristics differed significantly between the groups ; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group . At 15 years , 36.2 % of the original participants had dropped out of the study , and 30.9 % had not yet reached the time for their 15-year follow-up examination . RESULTS During the follow-up period , type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group , corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years , respectively ( adjusted hazard ratio with bariatric surgery , 0.17 ; 95 % confidence interval , 0.13 to 0.21 ; P bariatric surgery was influenced by the presence or absence of impaired fasting glucose ( P=0.002 for the interaction ) but not by BMI ( P=0.54 ) . Sensitivity analyses , including end-point imputations , did not change the overall conclusions . The postoperative mortality was 0.2 % , and 2.8 % of patients who underwent bariatric surgery required reoperation within 90 days owing to complications . CONCLUSIONS Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons . ( Funded by the Swedish Research Council and others ; Clinical Trials.gov number , NCT01479452 . )", "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 There is some evidence that quality of life ( QOL ) in patients with chronic obstructive pulmonary disease ( COPD ) may predict clinical outcomes and use of re sources . This study examined whether QOL scores could prospect ively predict re-admission for COPD or death within 12 months of an original admission , and whether QOL scores predicted home nebuliser provision . METHODS The study was carried out in all acute medical wards of Aberdeen Royal Infirmary , Woodend and City Hospitals , Aberdeen over 12 months . A total of 377 patients admitted with an exacerbation of COPD were identified in this time , 111 of whom were not included in the study because they refused the interview or died before discharge . The remaining 266 patients completed the St George 's Respiratory Question naire ( SGRQ ) . Information on spirometric parameters , nebuliser provision at discharge , provision of domiciliary oxygen , and re-admission within 12 months was collected from patient notes . RESULTS The mean age of the patients was 68 years and 53 % were men . The mean ( SD ) forced expiratory volume in one second ( FEV1 ) was 38.8 (18.0)% predicted and forced vital capacity ( FVC ) was 58.9 (23.8)% predicted . Higher ( worse ) scores on the SGRQ were significantly related to re-admission for COPD in the next 12 months ( difference = 4.8 , 95 % CI 1.6 to 8.0 ) . Patients who were re-admitted and died from COPD did not differ in SGRQ scores from those who were re-admitted and survived for more than 12 months . Re-admission was not related to sex , age , or pulmonary function . One hundred and thirty eight patients did not have a home nebuliser before admission . Of these , 14 were provided with a home nebuliser at discharge . Patients provided with nebulisers had significantly worse SGRQ scores and worse FVC . The 41 patients given domiciliary oxygen did not differ in SGRQ or spirometric parameters . Logistic regression analysis of the three SGRQ subscales ( Symptom , Impact and Activity ) , adjusting for lung function , age and sex , showed that all three subscales were significantly related to hospital readmission and that Impact scores were related to nebuliser provision . Women did not differ from men in Symptom scores on the SGRQ but differed markedly on the Activity and Impact scales . CONCLUSIONS It is concluded that poor scores on the SGRQ , a QOL scale which measures patient distress and coping , are associated with re-admission for COPD and use of re sources such as nebulisers , independent of physiological measures of disease severity", "PURPOSE Self-directed and supervised exercise were compared with usual care in a clinical trial design ed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer . PATIENTS AND METHODS One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life , aerobic capacity , and body weight . Participants were r and omly allocated to one of three intervention groups : usual care ( control group ) , self-directed exercise , or supervised exercise . Quality of life , aerobic capacity , and body weight measures were repeated at 26 weeks . The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks . RESULTS Physical functioning in the control group decreased by 4.1 points , whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups , respectively ( P = .04 ) . Post hoc analysis showed a moderately large ( and clinical ly important ) difference between the self-directed and control groups ( 9.8 points ; P = .01 ) and a more modest difference between the supervised and control groups ( 6.3 points ; P = .09 ) . No significant differences between groups were observed for changes in quality of life scores . In a secondary analysis of participants stratified by type of adjuvant therapy , supervised exercise improved aerobic capacity ( + 3.5 mL/kg/min ; P = .01 ) and reduced body weight ( -4.8 kg ; P chemotherapy . CONCLUSION Physical exercise can blunt some of the negative side effects of breast cancer treatment , including reduced physical functioning . Self-directed exercise is an effective way to improve physical functioning compared with usual care . In participants not receiving chemotherapy , supervised exercise may increase aerobic capacity and reduce body weight compared with usual care", "We have developed a rehabilitation programme at home and have investigated its effects on quality of life ( QOL ) , lung function , and exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . We studied 43 patients with severe airflow obstruction : forced expiratory volume in one second ( FEV1 ) 1.3 + /- 0.4 l ( mean + /- SD ) , FEV1/inspiratory vital capacity ( IVC ) 37 + /- 7.9 % . After stratification , 28 patients were r and omly allocated in a home rehabilitation programme for 12 weeks . Fifteen patients in a control group received no rehabilitation . The rehabilitation group received physiotherapy by the local physiotherapist , and supervision by a nurse and a general practitioner . Quality of life was assessed by the four dimensions of the Chronic Respiratory Question naire ( CRQ ) . We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea , emotion , and mastery . Lung function showed no changes in the rehabilitation group . The exercise tolerance improved significantly in the rehabilitation group compared to the control group . The improvement in quality of life was not correlated with the improvement in exercise tolerance . Rehabilitation of COPD patients at home may improve quality of life ; this improvement is not correlated with an improvement in lung function and exercise tolerance", "PURPOSE We report on a clinical trial developed to compare four different instruments that provide overall quality -of-life ( QOL ) scores , ranging from a simple , one-item instrument to more detailed instruments . Two issues addressed were ( 1 ) Will QOL tools suffer from missing data when used in a community-based cooperative group setting ? , and ( 2 ) Are there additional data generated by a more detailed multiitem instrument over that provided by a single-item global QOL question ? MATERIAL S AND METHODS A four-arm r and omized trial was design ed to compare four instruments that provide overall QOL scores in patients with advanced colorectal cancer . Patients and physicians completed the single-item Spitzer Uniscale ( UNISCALE ) at baseline and monthly . Patients were r and omly assigned to complete , in addition , either the 22-item Functional Living Index-Cancer ( FLIC ) , the five-item Spitzer QOL index ( QLI ) , a picture-face scale ( PICT ) , or nothing else . RESULTS A total of 128 patients were r and omized . Greater than 90 % complete QOL data were obtained . There was strong correlation , concordance , and criterion-related validity among all four patient-completed tools . The UNISCALE had a greater decrease over time than did the FLIC ( P=.005 ) , which suggests a greater sensitivity ; the UNISCALE was similar to the QLI and the PICT in this regard . Physicians provided lower UNISCALE scores than patients . Results supported the hypothesis that QOL is prognostic for survival . CONCLUSION Patients can effectively complete QOL tools in a cooperative group setting with proper education of health care providers and patients . A simple single-item tool ( UNISCALE ) appears to be appropriate to obtain a measure of overall QOL", "BACKGROUND AND PURPOSE The Rol and -Morris Question naire ( RMQ ) is a self-administered disability measure in which greater levels of disability are reflected by higher numbers on a 24-point scale . The RMQ has been shown to yield reliable measurements , which are valid for inferring the level of disability , and to be sensitive to change over time for groups of patients with low back pain . Little is known about the usefulness of this instrument in aiding decision making regarding individual patients . The purpose of this study was to determine the minimum level of detectable change when the RMQ is applied to individual patients . SUBJECTS The study sample consisted of 60 out patients with low back pain . METHODS The RMQ was administered at the subjects ' initial visit and again 4 to 6 weeks later . Conditional st and ard errors of measurement ( CSEMs ) were computed for initial and follow-up RMQ scores , and these values were used to estimate the minimum level of detectable change . Results . Minimum levels of detectable change at the 90 % confidence level varied from 4 to 5 RMQ points . CONCLUSION AND DISCUSSION The magnitude of CSEMs is sufficiently small to detect change in patients with initial scores in the central portion of the scale ( 4 - 20 RMQ points ) ; however , the magnitude is too large to detect improvement in patients with scores of less than 4 and deterioration in patients who have scores greater than 20", "PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program", "In this study , the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures , in order to identify the threshold where changes in clinical asthma measures are perceivable by patients . The study included 281 asthmatic patients , aged 18 - 63 yrs , in a r and omized , placebo-controlled clinical trial of a leukotriene antagonist . Changes were related in : 1 ) asthma symptom scores ; 2 ) inhaled beta-agonist use ; 3 ) forced expiratory volume in one second ( FEV1 ) ; and 4 ) peak expiratory flow ( PEF ) to a global question that queried overall change in asthma since starting the study drug . Additional analyses examined differences in the group reporting minimal improvement by treatment ( active treatment versus placebo ) , sex and age groups . The average minimal patient perceivable improvement for each measure was : 1 ) -0.31 points for the symptom score on a scale of 0 - 6 ; 2 ) -0.81 puffs x day(-1 ) for inhaled beta-agonist use ; 3 ) 0.23 L for FEV1 ; and 4 ) 18.79 L x min(-1 ) for PEF . In general placebo-treated patients and older patients , who reported minimal improvement , experienced less mean improvement from baseline than active-treated patients and younger patients , who reported minimal improvement . Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes . However , interpretation should be carried out cautiously when reporting a single value as a clinical ly important change", "OBJECTIVES : Endoscopy-negative gastroesophageal reflux disease ( GERD ) lacks objective markers of disease severity . Evaluation of therapies for GERD must therefore rely on subjective measures , including patient self-report question naires , to measure the clinical effectiveness of therapeutic interventions . We aim ed to evaluate the previously vali date d Gastrointestinal Symptoms Rating Scale ( GSRS ) and the Quality of Life in Reflux and Dyspepsia ( QOLRAD ) question naires for reliability and responsiveness to change over time . METHODS : Patients ( n = 1143 ) with heartburn , but no esophagitis included in a r and omized clinical trial assessing the effectiveness of active treatment with proton pump inhibitors over 4 wk were evaluated . RESULTS : The test-retest reliability of both question naires over time was good to excellent ( GSRS 0.53–0.69 ; QOLRAD 0.65–0.76 ) , as was the responsiveness estimated by st and ardized response means ( GSRS reflux dimension , −1.43 ; QOLRAD 0.81–1.43 ) and effect sizes ( GRSR reflux dimension , −1.74 ; QOLRAD 0.82–1.56 ) . The relationship between improvement in the GSRS reflux dimension score and the amount of clinical benefit as estimated by the patients themselves ( based on the Overall Treatment Evaluation ) suggested a minimally clinical relevant change is 0.5 on the seven grade d scales applied . The importance rating indicated that an important change in the GSRS reflux dimension and the QOLRAD dimensions is equivalent to 1.0 , and a very important change to 1.5 . CONCLUSIONS : The GSRS and QOLRAD are valid question naires that are reliable and sensitive to change . Both question naires should be suitable for use in clinical trials of therapeutic interventions for patients with heartburn", "Objectives : To establish a link between the minimal important difference ( MID ) and the st and ard error of measurement ( SEM ) for all responsive dimensions of the Asthma Quality of Life Question naire ( AQLQ ) . Methods : Secondary data analysis of baseline and follow-up interview data from 198 out patients with asthma enrolled in a r and omized controlled trial and receiving care at a major urban academic medical center 's general medicine clinics . Domain statistics for baseline and follow-up interviews were examined for the AQLQ . The baseline SEM values were compared with established AQLQ MID st and ards using weighted κ values . Results : One SEM identified the MID in responsive AQLQ dimensions . Weighted κ values ( 0.88–0.93 ) vali date d excellent agreement between these two criteria . Conclusion : This is the third study to support using one SEM to identify important individual change in health-related quality of life ( HRQoL ) measures . However , refinement of the process for determining a measure 's clinical ly meaningful differences is still needed to secure a link between the SEM and the identification of relevant HRQoL change over time", "BACKGROUND --Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease ( COPD ) . However , appropriately controlled studies have not previously been performed , nor have the benefits of different types of continuation programme for rehabilitation been investigated . Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD . METHODS --Thirty six patients with severe airways obstruction ( mean SD ) forced expiratory volume in one second ( FEV1 ) 1.3(0.4 ) 1 , FEV1/inspiratory vital capacity ( IVC ) 37.2(7.9)% ) were studied . Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner . During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session . Thereafter , 11 patients ( group A ) received a session of physiotherapy once weekly while 12 patients ( group B ) received a session of physiotherapy once a month . The control group C ( 13 patients ) received no rehabilitation at all . Quality of life was assessed by the Chronic Respiratory Question naire , exercise tolerance by the six minute walking distance , and lung function by FEV1 and IVC . Outcome measures were assessed at baseline and at three , six , 12 , and 18 months . RESULTS --Long term improvements in quality of life were found in patients in groups A and B , but not in those in group C compared with baseline , but these only reached significance in group B at all time points . Patients in group B had a higher quality of life than those in group C only at three and 12 months . There was a decrease in both six minute walking distance ( at 12 and 18 months ) and IVC ( at three , 12 , and 18 months ) in patients in group C compared with the baseline measurement . Between groups analysis showed no differences for six minute walking distance , FEV1 , and IVC . CONCLUSIONS --This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months . The change in quality of life was not associated with a change in exercise tolerance", "OBJECTIVE To compare the st and ard error of measurement ( SEM ) with established st and ards for clinical ly relevant intra-individual change in an evaluation of health-related quality of life . DESIGN Secondary analysis of data from a r and omized controlled trial . SUBJECTS Six hundred and five out patients with a history of cardiac problems attending the general medicine clinics of a major academic medical center . MEASURES Baseline and follow-up interviews included a modified version of the Chronic Heart Failure Question naire ( CHQ ) and the SF-36 . The SEM values corresponding to established st and ards for minimal clinical ly important differences ( MCIDs ) on the CHQ were determined . Individual change on the SF-36 was explored using the same SEM criterion . RESULTS One-SEM changes in this population corresponded well to the patient-driven MCID st and ards on all CHQ dimensions ( weighted kappas ( 0.87 ; P SEM to evaluate individual patient change should be explored among other health-related quality of life instruments with established st and ards for clinical ly relevant differences . Only then can it be determined whether the one-SEM criterion can be consistently applied as a proxy for clinical ly meaningful change", "To assess the impact of disease and treatment on patients with advanced non-small cell lung cancer ( NSCLC ) , we set out to determine a clinical ly meaningful change ( CMC ) on the Lung Cancer Subscale ( LCS ) and the Trial Outcome Index ( TOI ) of the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) question naire . We used data from Eastern Cooperative Oncology Group study 5592 ( E5592 ) , a r and omized trial comparing three chemotherapeutic regimens in 599 advanced NSCLC patients . Patients completed the FACT-L at baseline ( pretreatment ) , 6 weeks , 12 weeks , and 6 months . Comparing across baseline performance status ( 0 vs. 1 ) , prior weight loss ( or = 5 % ) , and primary disease symptoms ( 1 ) , LCS and TOI score differences ranged from 2.4 to 3.6 and 6.5 to 9.2 , respectively ( all Ps improvement in LCS score from baseline to 12 weeks was 2.4 points in patients who had responded to treatment versus 0.0 points in patients who had progressive disease . Twelve-week LCS change scores for patients progressing early were 3.1 points worse than those of patients progressing later ( mean = -1.2 vs.1.9 , respectively ) . Similarly , the average TOI change score from baseline to 12 weeks was -6.1 for patients who had progressive disease versus -0.8 points for patients who had responded to treatment . Twelve-week TOI change scores for patients progressing early ( mean = -8.1 ) were 5.7 points worse than those of patients progressing later ( mean = -8.1 vs. -2.4 , respectively ) . Analyses assuming nonr and om missing data result ed in slightly larger differences . Clinical ly relevant change scores were estimated as two to three points for the LCS and five to seven points for the TOI , setting upper limits for minimal CMCs . These values were comparable to suggested distribution-based criteria of a minimally important difference . These results support use of a two to three point change in the LCS and five to six point change on the TOI of the FACT-L as a CMC , and offer practical direction for inclusion of important patient-based endpoints in lung cancer clinical trials", "The purpose was to determine the minimally important clinical difference ( MICD ) in fatigue as measured by the Profile of Mood States , Schwartz Cancer Fatigue Scale ( SCFS ) , General Fatigue Scale , and a 10-point single-item fatigue measure . The MICD is the smallest amount of change in a symptom ( e.g. , fatigue ) measure that signifies an important change in that symptom . Subjects rated the degree of change in their fatigue over 2 days on a Global Rating Scale . 103 patients were enrolled on this multisite prospect i ve repeated measures design . MICD was determined following established procedures at two time points . Statistically significant changes were observed for moderate and large changes in fatigue , but not for small changes . The scales were sensitive to increases in fatigue over time . The MICD , presented as mean change , for each scale and per item on each scale is : POMS = 5.6 , per item = 1.1 , SCFS = 5.0 , per item = 0.8 , GFS = 9.7 , per item = 1.0 , and the single item measure of fatigue was 2.4 points . This information may be useful in interpreting scale scores and planning studies using these measures", "The use of quality -of-life indices in therapeutic trials is gaining recognition as important outcome variables for evaluating the total impact of antihypertensive therapy . While the statistical significance of treatment differentials in quality -of-life indices has been well documented , their clinical relevance still remains unclear . The interpretation of clinical trial quality -of-life treatment differentials depends on a clear underst and ing of the normal variability in the index due to changes in day-to-day living and the relationship between the size of the differential and shifts in population responses . Using the results from a large-scale r and omized clinical trial on quality of life and antihypertensive therapy , a rationale for the interpretation of clinical trial results for use by the practicing clinician is presented", "OBJECTIVES To report on the further development of the Incontinence Quality of Life Instrument ( I-QOL ) , a self-report quality of life measure specific to urinary incontinence ( UI ) , including its measurement model , responsiveness , and effect size . METHODS Incontinent female patients ( 141 with stress , 147 with mixed UI ) completed the I-QOL and comparative measures at screening , pretreatment , and four subsequent follow-up visits during participation in a multicenter , double-blind , placebo-controlled , r and omized trial assessing the efficacy of duloxetine . Psychometric testing followed st and ardized procedures . RESULTS Factor analysis confirmed an overall score and three subscale scores ( avoidance and limiting behaviors , psychosocial impacts , and social embarrassment ) . All scores were internally consistent ( alpha = 0.87 to 0.93 ) and reproducible ( ICC = 0.87 to 0.91 ) . The pattern of previously reported correlations with the Short-Form 36-item Health Survey and Psychological Well-Being Schedule were confirmed . Responsiveness statistics using changes in the independent measures of stress test pad weight , number of incontinent episodes , and patient global impression of improvement ranged from 0.4 to 0.8 . Minimally important changes ranged from 2 % to 5 % in association with these measures and effect sizes . CONCLUSIONS In a clinical trial , the I-QOL proved to be valid , reproducible , and responsive to treatment for UI in women", "OBJECTIVE To estimate minimal clinical ly important differences ( MCID ) of effects measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) in patients with osteoarthritis ( OA ) of the lower extremities undergoing a comprehensive inpatient rehabilitation intervention . METHODS A prospect i ve cohort study assessed patients ' health by the WOMAC at baseline ( entry into the clinic ) and at the 3 month followup , and by a transition question naire asking about the change of \" health in general related to the OA joint \" during that time period . The WOMAC section score differences between the \" equal \" group and the \" slightly better \" and \" slightly worse \" groups result ed in the MCID for improvement and for worsening . RESULTS In total 192 patients were followed up . The MCID for improvement ranged from 0.80 to 1.01 points on the continuous WOMAC numerical rating scale from 0 to 10 , reflecting changes of 17 to 22 % of baseline scores . The MCID for worsening conditions ranged from 0.29 ( 6 % ) to 1.03 points ( 22 % ) . In the transition reply subjectively unchanged patients reported a \" pessimistic bias \" of 0.35 to 0.51 points , except for the stiffness section . Both MCID and pessimistic bias showed regression to the mean and baseline dependency . CONCLUSION The assessment of MCID using the transition method is a heuristic and valid strategy to detect particular rehabilitation effects in patients with OA of the lower extremities with the use of the WOMAC , and it is worth implementing . The size of the MCID and of the systematic bias is comparable to that assessed by other methods and in other therapeutic setting", "OBJECTIVE To discuss the concepts of the minimal clinical ly important difference ( MCID ) and the smallest detectable difference ( SDD ) and to examine their relation to required sample sizes for future studies using concrete data of the condition-specific Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and the generic Medical Outcomes Study 36-Item Short Form ( SF-36 ) in patients with osteoarthritis of the lower extremities undergoing a comprehensive inpatient rehabilitation intervention . METHODS SDD and MCID were determined in a prospect i ve study of 122 patients before a comprehensive inpatient rehabilitation intervention and at the 3-month followup . MCID was assessed by the transition method . Required SDD and sample sizes were determined by applying normal approximation and taking into account the calculation of power . RESULTS In the WOMAC sections the SDD and MCID ranged from 0.51 to 1.33 points ( scale 0 to 10 ) , and in the SF-36 sections the SDD and MCID ranged from 2.0 to 7.8 points ( scale 0 to 100 ) . Both question naires showed 2 moderately responsive sections that led to required sample sizes of 40 to 325 per treatment arm for a clinical study with unpaired data or total for paired followup data . CONCLUSION In rehabilitation intervention , effects larger than 12 % of baseline score ( 6 % of maximal score ) can be attained and detected as MCID by the transition method in both the WOMAC and the SF-36 . Effects of this size lead to reasonable sample sizes for future studies lying below n = 300 . The same holds true for moderately responsive question naire sections with effect sizes higher than 0.25 . When design ing studies , assumed effects below the MCID may be detectable but are clinical ly meaningless", "Changes in health-related quality of life ( HRQoL ) were evaluated in patients with chronic obstructive pulmonary disease ( COPD ) following treatment with placebo , salmeterol 50 microg twice a day or 100 microg twice a day by metered-dose inhaler . Patients completed the disease-specific St. George 's Respiratory Question naire ( SGRQ ) and the Medical Outcomes Study Short Form 36 ( SF-36 ) at baseline and after 16 wk of treatment . Data from 283 patients ( 95 patients in the placebo group and 94 in each salmeterol group ) were available for HRQoL analysis . Apart from a small difference in ages , all treatment groups were well matched at baseline in terms of forced expiratory volume in one second ( FEV1 ) and HRQoL scores . Compared with placebo , salmeterol 50 microg twice a day was associated with significant improvements in SGRQ \" Total \" and \" Impacts \" scores which exceeded the threshold for a clinical ly significant change . This was not seen with salmeterol 100 microg twice a day . Changes in SGRQ and SF-36 scores correlated . They also showed a weak but significant relationship with FEV1 . This study has shown that a modest change in lung function may be associated with clinical ly significant gain in health and well-being in COPD patients" ]

[ "Abstract This long-term extension of an 8-week r and omized , naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam ( n = 47 ) and paroxetine ( n = 37 ) over a 3-year total treatment duration . Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine ( both taken at bedtime ) . This study reports data from the long-term period ( 34 months ) , following the initial 8-week treatment phase . Thus , total treatment duration was 36 months . Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine , but patients with partial primary treatment success were switched to the combination therapy . At initiation of the long-term study , the mean doses of clonazepam and paroxetine were 1.9 ( SD , 0.30 ) and 38.4 ( SD , 3.74 ) mg/d , respectively . These doses were maintained until month 36 ( clonazepam 1.9 [ SD , 0.29 ] mg/d and paroxetine 38.2 [ SD , 3.87 ] mg/d ) . Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine ( mean difference : CGI-Severity scale −3.48 vs −3.24 , respectively , P = 0.02 ; CGI-Improvement scale 1.06 vs 1.11 , respectively , P = 0.04 ) . Both treatments similarly reduced the number of panic attacks and severity of anxiety . Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine ( 28.9 % vs 70.6 % , P efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course . There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events", " Background Anxiety disorders are among the most common psychiatric illnesses , with generalized anxiety disorder ( GAD ) being one of the most common . Sleep disturbances are highly prevalent in GAD patients . While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials , mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin . Thus , the objective of this study was to model the longitudinal latent effect of pregabalin or usual care ( UC ) therapies on changes in sleep in out patients with GAD under routine clinical practice . Methods Male and female GAD out patients , aged 18 years or above , from a 6-month prospect i ve noninterventional trial were analyzed . Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms ( assessed with Hamilton Anxiety Scale ) and sleep disturbances ( assessed with Medical Outcomes Study -Sleep Scale [ MOS-S ] ) were estimated by a conditional latent curve model applying structural equation modeling . Results A total of 1,546 pregabalin-naïve patients were analyzed , 984 receiving pregabalin and 562 UC . Both symptoms of anxiety and sleep disturbances were significantly improved in both groups , with higher mean ( 95 % confidence interval ) score reductions in subjects receiving pregabalin : −15.9 ( −15.2 ; −16.6 ) vs −14.5 ( −13.5 ; −15.5 ) , P=0.027 , in Hamilton Anxiety Scale ; and −29.7 ( −28.1 ; −31.3 ) vs −24.0 ( −21.6 ; −26.4 ) , P , in MOS-S. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant ( γ = −3.99 , P reduction in anxiety symptoms . A mediation model showed that 70 % of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement . Conclusion A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect , not mediated by improvements in anxiety symptoms", "Background : Remission has become one of the leading outcome criteria in clinical trials . Data collected by this research group assessed the rate of remission after 6 months of treatment of generalized anxiety disorder ( GAD ) with venlafaxine XR , to search for predictors of remission and to define how early on in treatment later remission can be predicted . Method : Two hundred sixty-eight patients with a GAD diagnosis enrolled into an open-label 6-month-treatment trial with venlafaxine XR ( 75 - 225 mg/day ) . Remission was defined by a Hamilton anxiety scale total score ≤7 . Logistic regression approaches were used to find out how early on in treatment later remission could be predicted , as well as to determine predictors of remission . In addition , adverse events were also followed over time . Results : While the total enrolled patient sample ( n = 268 ) had a remission rate of 53 % , 6-month completers ( n = 159 ) had a remission rate of 79 % . The only statistically significant predictor of remission , independent of baseline anxiety and depression levels , was a low Eysenck neuroticism score . The remission status outcome could best be predicted after 8 weeks of treatment when a CGI-I score of 1 or 2 predicted later remission with 78 % accuracy and later nonremission with 91 % accuracy . The incidence of adverse events decreased over the 6-month period , with sexual adverse events decreasing the least . Conclusion : The only significant predictor of remission was a low score on the Eysenck neuroticism scale . The earliest reliable prediction of later remission , based on improvement , could be made after 8 weeks of treatment with 91 % accuracy", "Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies . This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder . Patients who satisfactorily completed a 12-week , double-blind , placebo-controlled study of paroxetine and clomipramine could choose to continue receiving their r and omized treatment for a further 36 weeks . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression Scale , the Hamilton Anxiety Rating Scale , the Marks Sheehan Phobia Scale and the Sheehan Disability Scale . In total , 176 patients were included in the intention-to-treat population . The number of full panic attacks decreased in all three groups during the 12-week study , and improvements continued with long-term therapy . Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks , and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks . There were no significant differences between paroxetine and clomipramine . The proportion of patients who withdrew from the study due to adverse effects was greater in the clomipramine group ( 19 % ) than in either the paroxetine group ( 7 % ) or the placebo group ( 9 % ) . Paroxetine was significantly more effective than placebo and as effective as ( but better tolerated than ) clomipramine in the long-term treatment of panic disorder . Not only was efficacy maintained , but continued improvement was also seen , indicating the importance of long-term treatment in patients with panic disorder", "Variation in genes involved in serotonergic signaling is thought to be associated with antidepressant treatment response in generalized anxiety disorder ( GAD ) . We examined a possible interaction between the serotonin transporter gene ( SLC6A4 ) 5-HTTLPR/rs25531 haplotype and the serotonin 2A receptor gene ( HTR2A ) single-nucleotide polymorphism ( SNP ) rs7997012 in antidepressant treatment outcome in GAD . Patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study . Genotypes obtained for the 5-HTTLPR/rs25531 ( La/La , La/S or S/S ) haplotype and rs7997012 SNP ( G or A ) in the European American population ( n=112 ) were used for pharmacogenetic analysis . Our data show that subjects with genotypes La/La+G/G or La/La+G/A ( n=28 ) had significantly lower Hamilton Anxiety Scale ( HAM-A ) scores than those with genotypes La/S+A/A or S/S+A/A ( n=12 ) at 6 months ( HAM-A difference=10.7 ; P HAM-A differences of 4.3 ( 5-HTTLPR/rs25531 : La/La versus La/S+S/S ) and 4.8 ( rs7997012 : G/G+G/A versus A/A ) , showing for the first time a significant gene – gene interaction between these markers", "The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) as maintenance monotherapy for patients with generalized anxiety disorder ( GAD ) . Time-to-event ( anxiety symptom recurrence ; maximum 52 weeks ) multicenter , r and omized-withdrawal , parallel-group , double-blind , placebo-controlled study of quetiapine XR ( 50–300 mg/day ) following open-label run-in ( 4–8 weeks ) and open-label stabilization ( ≥12 weeks ) . Primary variable : time from r and omization to anxiety event . Secondary variables included : Hamilton Anxiety Rating Scale ( HAM-A ) total , HAM-A psychic/somatic anxiety factors , Clinical Global Impression-Severity of Illness ( CGI-S ) , and Quality of Life , Enjoyment and Satisfaction Question naire ( Q-LES-Q ) scores ; adverse events ( AE ) reporting . Four hundred and thirty-two patients , stabilized on quetiapine XR , were r and omized to continue quetiapine XR ( N=216 ) or switch to placebo ( N=216 ) . Risk of anxiety symptom recurrence was significantly reduced by 81 % for quetiapine XR versus placebo : hazard ratio=0.19 ( 95 % confidence interval 0.12–0.31 ; P receiving quetiapine XR ( N=22 , 10.2 % ) than placebo ( N=84 , 38.9 % ) experienced anxiety symptom recurrence . Significant differences were observed between quetiapine XR and placebo in : HAM-A total , psychic/somatic , CGI-S ( all P Q-LES-Q ( P 10 % ) during open-label treatment were dry mouth , sedation , somnolence , dizziness , fatigue , and constipation . During r and omized treatment , the most common AEs for quetiapine XR were headache and nasopharyngitis . Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR , with tolerability results consistent with the known profile of quetiapine ", "The pituitary adenylate cyclase-activating peptide ( PACAP ) and its receptor ( PAC1 ) are involved in stress response and anxiety . Genotypes for PACAP/PAC1 were examined for effects on treatment response to venlafaxine XR in generalized anxiety disorder . The Asp54Gly ( rs2856966 ) variant in the PACAP gene was associated with better treatment outcome ", "BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients", "BACKGROUND Existing literature on panic disorder ( PD ) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy ( CBT ) , Selective Serotonin Reuptake Inhibitor ( SSRI ) or both combined ( CBT+SSRI ) . METHOD Patients were r and omized to CBT , SSRI or CBT+SSRI which each lasted one year including three months of medication taper . Participating patients kept record of the frequency of panic attacks throughout the full year of treatment . Rate of improvement on panic frequency and the relationship between rate of improvement and baseline agoraphobia ( AG ) were examined . RESULTS A significant decline in frequency of panic attacks was observed for each treatment modality . SSRI and CBT+SSRI were associated with a significant faster rate of improvement as compared to CBT . Gains were maintained after tapering medication . For patients with moderate or severe AG , CBT+SSRI was associated with a more rapid improvement on panic frequency as compared to patients receiving either mono-treatment . LIMITATIONS Frequency of panic attacks was not assessed beyond the full year of treatment . Second , only one process variable was used . CONCLUSIONS Patients with PD respond well to each treatment as indicated by a significant decline in panic attacks . CBT is associated with a slower rate of improvement as compared to SSRI and CBT+SSRI . Discontinuation of SSRI treatment does not result in a revival of frequency of panic attacks . Our data suggest that for patients without or with only mild AG , SSRI-only will suffice . For patients with moderate or severe AG , the combined CBT+SSRI treatment is recommended", "One hundred six patients diagnosed according to DSM-III as suffering from agoraphobia with panic disorder , panic disorder with limited phobic avoidance , or uncomplicated panic disorder entered an acute 8-week treatment phase . Patients who improved received an additional 6 months ' maintenance treatment . Significantly more patients treated with alprazolam than with imipramine hydrochloride or placebo remained in therapy and experienced panic attack and phobia relief during the acute treatment phase . During the maintenance phase , neither tolerance nor daily dose increase was observed . All patients who completed the maintenance phase ( 27 in the alprazolam group , 11 in the imipramine group , and 10 in the placebo group ) were panic free at the end of 8 months of study treatment . Alprazolam therapy was effective and well tolerated at a mean daily dose of 5.7 mg . Imipramine hydrochloride ( 175 mg/d ) also produced significant panic relief but was associated with poor patient acceptance", "OBJECTIVE Older adults with anxiety disorders are burdened by impairment in neurocognition , which may be mediated by elevated circulating cortisol levels . In a r and omized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder , we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function . METHODS We examined 60 adults aged 60 years and older , who took part in a 12-week trial of escitalopram versus placebo for generalized anxiety disorder . All subjects had pre-treatment and post-treatment assessment s that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation . RESULTS Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory but no association with executive tasks ( measures of working memory and set shifting ) . Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes : memory improvement was seen with cortisol reduction among patients receiving escitalopram but not among patients receiving placebo . CONCLUSION Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of generalized anxiety disorder predicted changes in immediate and delayed memory . This finding suggests a novel treatment strategy in late-life anxiety disorders : targeting hypothalamic-pituitary- adrenal axis dysfunction to improve memory", "Discontinuation effects following cessation of 12 and 24 wk of pregabalin treatment for generalized anxiety disorder ( GAD ) were evaluated in a placebo- and lorazepam-controlled , r and omized , double-blind , multicentre trial conducted in 16 countries . The study design consisted of two 12-wk treatment periods ( periods 1 and 2 ) , each followed by a 1-wk taper and two post-discontinuation assessment s , one immediately following the taper and one 1-wk post-taper . Patients were assigned to receive an initially flexible dose of pregabalin 450 - 600 mg/d , pregabalin 150 - 300 mg/d , or lorazepam 3 - 4 mg/d for 6 wk ; responders continued fixed-dose therapy for 6 additional weeks . Patients entering period 2 continued on the same fixed dose or switched to placebo . Discontinuation effects were evaluated with the Physician Withdrawal Checklist ( PWC ) and reported discontinuation-emergent signs and symptoms . Rebound anxiety was measured with the Hamilton Anxiety Rating Scale . GAD symptoms improved with all treatments and improvements were maintained over 12 and 24 wk . Low levels of discontinuation symptoms were evident in all treatment groups . For patients who received active treatment during both periods , mean ( 95 % confidence interval ) increases on the PWC from last visit on active treatment to the second post-discontinuation assessment were : pregabalin 450 - 600 mg/d : 2.8 ( 1.6 - 3.9 ) , pregabalin 150 - 300 mg/d : 1.7 ( 0.7 - 2.8 ) , lorazepam 3 - 4 mg/d : 2.2 ( 1.0 - 3.5 ) . Rates of rebound anxiety were also low at both 12 and 24 wk ( 0 - 6 % ) . This suggests that risk of discontinuation symptoms and rebound anxiety are low for pregabalin after 12 and 24 wk of treatment", "Objective : To eluci date the consequences of broadening DSM-IV criteria for generalized anxiety disorder ( GAD ) , we examined prospect ively the evolution of GAD symptoms in two groups of patients ; one group diagnosed according to DSM-IV criteria and the other , according to broader criteria . Method : Multicentre , prospect i ve and observational study conducted on outpatient psychiatric clinics . Patients were selected from October 2007 to January 2009 and diagnosed with GAD according to DSM-IV criteria ( DSM-IV group ) or broader criteria . Broader criteria were considered 1-month of excessive or non-excessive worry and only 2 of the associated symptoms listed on DSM-IV for GAD diagnosis . Socio-demographic data , medical history and functional outcome measures were collected three times during a 6-month period . Results : 3,549 patients were systematic ally recruited ; 1,815 patients in DSM-IV group ( DG ) and 1,264 in broad group ( BG ) ; 453 patients did not fulfil inclusion criteria and were excluded . Most patients ( 87.9 % in DG , 82.0 % in BG ) were currently following pharmacological therapies ( mainly benzodiazepines ) to manage their anxiety symptoms . The changes observed during the study were : 49.0 % and 58.0 % , respectively of patients without anxiety symptoms as per HAM-A scale at the 6 month visit ( p=0.261 ) and 59.7 % and 67.7 % , respectively ( p=0.103 ) of responder rates ( > 50 % reduction of baseline scoring ) . Conclusion : Broadening of GAD criteria does not seem to affect psychiatric care results in subjects with GAD , is able to identify the core symptoms of the disease according to the DSM-IV criteria and could lead to an earlier diagnosis", "Background This naturalistic open label follow-up study had three objectives :1 ) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment2 ) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia.3 ) To observe paroxetine 's tolerability over a 24 month period . Methods 143 patients with panic disorder ( PD ) , with or without agoraphobia , successfully finished a short-term ( ie 12 week ) trial of paroxetine treatment . All patients then continued to receive paroxetine maintenance therapy for a total of 12 months . At the end of this period , 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase . The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored , as in the first group , for another year while medication-free . The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a r and omized manner . Results Only 21 of 143 patients ( 14 % ) relapsed during the one year medication discontinuation follow-up phase . There were no significant differences in relapse rates between the patients who received intermediate-term ( up to 12 months ) paroxetine and those who chose the long-term course ( 24 month paroxetine treatment ) . 43 patients ( 30.1 % ) reported sexual dysfunction . The patients exhibited an average weight gain of 5.06 kg . All patients who eventually relapsed demonstrated significantly greater weight increase ( 7.3 kg ) during the treatment phase . Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation . Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment", "CONTEXT Generalized anxiety disorder ( GAD ) is a chronic disorder in need of reliable data to guide long-term treatment . OBJECTIVES To assess the benefits of 6 and 12 months ' treatment of GAD with venlafaxine hydrochloride extended release ( XR ) in patients who improved after 6 months ' open-label venlafaxine XR treatment . DESIGN After 6 months ' open-label venlafaxine XR treatment , improved patients were r and omized to venlafaxine XR or placebo for 6 months . All venlafaxine XR patients still in the study at 12 months were r and omized to receive venlafaxine XR or placebo , and all placebo patients continued taking placebo for another 6 months . SETTING One urban site ( 5 locations ) . PATIENTS Of 268 patients with a diagnosis of GAD entering the open-label venlafaxine XR treatment phase , 158 ( 59.0 % ) completed 6 months , and 136 ( 50.7 % ) entered relapse phase 2 ( 6 - 12 months ) . Fifty-nine ( 43.4 % ) of 136 patients entered phase 3 ( 12 - 18 months ) . INTERVENTION Six months ' open-label treatment with venlafaxine XR , followed by double-blind venlafaxine XR or placebo for 2 relapse phases , each lasting 6 months . MAIN OUTCOME MEASURES Time to relapse while receiving venlafaxine XR or placebo after 6 and after 12 months of treatment . Relapse was strictly defined to safeguard against assigning patients with venlafaxine XR discontinuation symptoms or temporary anxiety increase as relapse . RESULTS For objective 1 , relapse rates in phase 2 ( months 6 - 12 ) were 9.8 % on venlafaxine XR and 53.7 % on placebo ( P relapse rates after 12 months on placebo ( 32.4 % ) were lower than after 6 months on venlafaxine XR ( 53.7 % ) ( P < .03 ) . CONCLUSIONS Treatment of GAD with an antidepressant should be continued for at least 12 months . Preliminary data demonstrate that improved patients who relapse while off their antianxiety medication after at least 6 months of treatment will again most likely respond to a second course of treatment with the same medication . Trial Registration clinical trials.gov Identifier : NCT00183274", "Background We evaluated the effects of once-daily extended-release quetiapine fumarate ( quetiapine XR ) on patient-reported outcomes in generalized anxiety disorder ( GAD ) . Methods This is a report of a pooled analysis from three acute 8-week , r and omized , placebocontrolled , fixed-dose ( 50 , 150 , 300 mg/day ) studies and a 52-week maintenance flexible dose ( 50–300 mg/day ) study of quetiapine XR monotherapy in patients with GAD . Quality of Life Enjoyment and Satisfaction Question naire Short Form ( Q-LES-Q-SF ) percent maximum total scores ( items 1–14 ) , item 15 ( “ satisfaction with medication ” ) , item 16 ( “ overall life satisfaction ” ) , and Pittsburgh Sleep Quality Index ( PSQI ) global scores are reported . Sheehan Disability Scale ( SDS ) total scores were also assessed ( maintenance study only ) . Results The acute studies showed significant improvements at week 8 in Q-LES-Q-SF percent maximum total score with quetiapine XR 150 mg/day ( P 16 with quetiapine XR 50 ( P versus placebo ; PSQI global scores significantly improved with quetiapine XR 50 , 150 , and 300 mg/day versus placebo ( P versus placebo with quetiapine XR 50–300 mg/day in Q-LES-Q-SF percent total score , item 15 and item 16 scores , PSQI global score , and SDS total score . Conclusion Quetiapine XR 150 mg/day ( acute studies ) and 50–300 mg/day ( maintenance study ) improved quality of life , overall functioning , and sleep quality in patients with GAD", "BACKGROUND This investigation assessed the effect of personality disorders ( PersDs ) on time to remission in patients with generalized anxiety disorder , social phobia , or panic disorder . METHODS Selected Axis I and II predictors of time to remission during 5 years of follow-up were assessed in 514 patients with 1 or more of these anxiety disorders who participated in the Harvard/Brown Anxiety Research Program , a multisite , prospect i ve , longitudinal , naturalistic study . RESULTS The presence of a PersD predicted a 30 % lower likelihood of generalized anxiety disorder remission , a 39 % lower likelihood of social phobia remission , and no difference in likelihood of panic disorder remission . More specifically , a lower likelihood of remission from generalized anxiety disorder was predicted by the presence of avoidant PersD ( 34 % lower ) and dependent PersD ( 14 % lower ) . The presence of avoidant PersD predicted a 41 % lower likelihood of social phobia remission . The presence of major depressive disorder did not account for these findings . CONCLUSIONS Our findings provide new data on the pernicious effect of PersDs on the course of generalized anxiety disorder and social phobia but not panic disorder , suggesting that PersDs have a differential effect on the outcome of anxiety disorders", "BACKGROUND Controlled prospect i ve studies of the simultaneous long-term outcome of several mental disorders are rare . This study sought to determine if there were important differences between the outcome of anxiety and depressive disorders after 12 years and to examine their main predictors . METHOD A cohort of 210 people seen in general practice psychiatric clinics with a DSM-III diagnosis of generalized anxiety disorder ( 71 ) , panic disorder ( 74 ) , or dysthymic disorder ( 65 ) , including combined anxiety-depressive disorder ( cothymia ) ( 67 ) was followed up after 12 years . Interview assessment s of symptoms , social functioning and outcome were made , the latter using a new scale , the Neurotic Disorder Outcome Scale . Seventeen baseline predictors were also examined . RESULTS Data were obtained from 201 ( 96 % ) patients , 17 of whom had died . Only 73 ( 36 % ) had no DSM diagnosis at the time of follow-up . Using univariate and stepwise multiple linear regression those with cothymia , personality disorder , recurrent episodes and greater baseline self-rated anxiety and depression ratings had a worse outcome than others ; initial diagnosis did not contribute significantly to outcome and instability of diagnosis over time was much more common than consistency . CONCLUSION Only two out of five people with the common neurotic disorders have a good outcome despite alleged advances in treatment . Those with greater mood symptoms and pre-morbid personality disorder have the least favourable outcome . It is suggested that greater attention be paid to the concurrent treatment of personality disorder and environmental factors rather than symptoms as these may be the real cause of apparent treatment resistance", "Carbon dioxide ( CO2 ) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder ( PD ) . Anti-panic drugs decrease CO2 reactivity after the first days of treatment ; however , the clinical meaning of this finding has not yet been established . This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors ( SSRIs ) on CO2 reactivity and compared the relationships between 35 % CO2 hyperreactivity modulation and short-term clinical outcome . One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were r and omly assigned to treatment groups with imipramine , clomipramine , paroxetine , sertraline , or fluvoxamine . A double-blind , r and omized design was applied . Each patient received the 35 % CO2 challenge on days 0 , 7 , and 30 . The severity of clinical symptomatology was measured on days 0 and 30 . Decreased hyperreactivity to 35 % CO2 in all five treatment groups was already evident after the first week . The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement . Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month . The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity . They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “ respiratory ” PD", "BACKGROUND Generalized anxiety disorder ( GAD ) is a common and serious disease with a lifetime prevalence of 4.3 % to 5.9 % . It is underdiagnosed in primary care . METHODS Recommendations on the treatment of GAD are given on the basis of all available findings from pertinent r and omized trials , retrieved by a selective search of the literature . RESULTS Among psychotherapeutic techniques , various kinds of cognitive behavioral therapy ( CBT ) have been found useful in controlled trials . The drugs of first choice include selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-norepinephine reuptake inhibitors ( SNRIs ) , and the calcium-channel modulator pregabalin . Tricyclic antidepressants are also effective but have more adverse effects than SSRIs . Although benzodiazepines are effective anxiolytic agents for short-term use , they should not be given over the long term because of the danger of addiction . Buspirone , an azapirone , was found to be effective in a small number of trials , but the findings across trials are inconsistent . The response rate of GAD to CBT in published studies lies between 47 % and 75 % , while its response rate to drug treatment lies between 44 % and 81 % . CONCLUSION The treatment of GAD with CBT and drugs is evidence -based and has a good chance of improving the manifestations of the disorder", "OBJECTIVE This study evaluated the efficacy and tolerability of agomelatine in the prevention of relapse in patients with generalized anxiety disorder ( GAD ) . METHOD Patients with GAD ( Hamilton Anxiety Rating Scale [ HARS ] ≥ 22 , with items 1 and 2 ≥ 2 , item 1 + 2 ≥ 5 ; Montgomery-Asberg Depression Rating Scale [ MADRS ] ≤ 16 ; and HARS total score between screening and baseline ) who responded to a 16-week course of agomelatine 25 - 50 mg/d treatment were r and omly assigned to receive continuation treatment with agomelatine ( n = 113 ) or placebo ( n = 114 ) for 26 weeks . The main outcome measure was time to relapse during this maintenance period . The estimated risk of relapse was calculated using the Kaplan-Meier method , and groups were compared using a log-rank test stratified for country . The study was undertaken in 31 clinical centers in Canada , Denmark , Estonia , Finl and , Hungary , and Sweden from November 2007 to September 2009 . RESULTS During the 6-month maintenance period , the proportion of patients that relapsed during the double-blind period in the agomelatine group ( 22 patients , 19.5 % ) was lower than in the placebo group ( 35 patients , 30.7 % ) . The risk of relapse over time was significantly lower for patients who continued treatment than for those switched to placebo ( P = .046 , log-rank test stratified for country ) . Agomelatine was also superior to placebo in preventing relapse in the subset of more severe patients with baseline HARS total score ≥ 25 and CGI-S score ≥ 5 . The tolerability of agomelatine was good throughout the study , and there were no differences in discontinuation symptoms after withdrawal of agomelatine in comparison to maintenance on agomelatine . CONCLUSIONS The present study extends the positive findings of an earlier short-term study of agomelatine in GAD , demonstrating that agomelatine is effective and well-tolerated in the longer-term treatment of this chronic disorder . TRIAL REGISTRATION www.is rct n.org identifier : IS RCT N38094599", "OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders", "To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines , out patients ( N = 106 ) with a lifetime diagnosis of generalized anxiety disorder ( current diagnosis could be subthreshold ) who had been treated with a benzodiazepine for 8–52 weeks were stabilized for 2–4 weeks on alprazolam in the range of 1–4 mg/day . Patients were then r and omized to 12 weeks of double-blind treatment with either pregabalin 300–600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25 % per week , followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment . Outcome measures included ability to remain benzodiazepine-free ( primary ) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist ( PWC ) . At endpoint , a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo ( 51.4 % vs 37.0 % ) . Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo ( −2.5 vs + 1.3 ; p endpoint mean PWC scores ( 6.5 vs 10.3 ; p = 0.012 ) . Thirty patients ( 53 % ) in the pregabalin group and 19 patients ( 37 % ) in the placebo group completed the study , reducing the power to detect a significant difference on the primary outcome . The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy", "A multicenter , r and omized , placebo-controlled , double-blind study was conducted to evaluate the efficacy of pregabalin in preventing relapse of generalized anxiety disorder ( GAD ) after response to short-term treatment . Out patients ( n=624 ) with GAD for ≥1 year received open-label pregabalin ( 450 mg/day ) for 8 weeks and , if a clinical response was observed , were r and omized to receive either pregabalin ( 450 mg/day ; n=168 ) or placebo ( n=170 ) for 24 weeks . The primary efficacy parameter was time to relapse . Among responders to open-label acute treatment with pregabalin , time to relapse of GAD was significantly longer for patients treated with pregabalin compared with placebo ( P the placebo group had relapsed by day 23 , and at study endpoint , 65 % had relapsed . In the pregabalin group , only 42 % had relapsed by study end . Total attrition during double-blind treatment was somewhat higher on pregabalin compared with placebo ( 21.4 vs. 15.3 % ) ; attrition owing to adverse events ( AEs ) was also somewhat higher on pregabalin ( 6.0 vs. 2.4 % ) . AEs were relatively low in the double-blind phase ; only three AEs occurred with an incidence of more than 5 % on pregabalin and placebo , respectively : infection ( 14.9 vs. 11.2 % ) , headache ( 10.1 vs. 11.2 % ) , and somnolence ( 6.0 vs. 0 % ) . No safety concerns were identified with long-term treatment . The study indicates that pregabalin is an effective treatment for the prevention of relapse in patients with GAD", "OBJECTIVE This study aims to evaluate the differential predictive values of age , age of onset and duration of illness on paroxetine and cognitive-behavioural therapy ( CBT ) outcome in late-life panic disorder with agoraphobia . METHOD Patients 60 years and older with a confirmed diagnosis of panic disorder with agoraphobia ( n = 49 ) were r and omly assigned to paroxetine ( 40 mg/day ) treatment , individual CBT or a waiting-list control condition . Multiple regression analyses were conducted per treatment arm with post-treatment avoidance behaviour and agoraphobic cognitions as the dependent variables . RESULTS Higher age at onset and shorter duration of illness were predictors of superior outcomes following CBT , although these variables did not influence the treatment effects of paroxetine . CONCLUSIONS In late-life agoraphobic panic disorder , chronological age has no impact on treatment modality outcome . In older patients with a late disease onset or shorter duration of illness , CBT is to be preferred over paroxetine , whereas paroxetine might be the treatment of choice for older people with an early onset and short duration of illness", "It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse . This study further explores the relationship between relapse and duration of imipramine treatment in this population . Fifty-one patients , all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and r and omized to double-blind maintenance or placebo substitution , discontinued imipramine treatment eventually and were followed over a 12-month risk period : 27 during first year placebo substitution , 7 after 12 months of imipramine maintenance in placebo substitution , and 17 after variable duration s of imipramine maintenance in open discontinuation . There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation . Duration of imipramine treatment , the method of discontinuation ( open versus placebo substitution ) , or any of the 9 variables from the demographic , clinical , and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse . The rate of relapse after only 6 months of treatment ( 10 out of 27 , 37 % ) was identical to the rate of relapse after 12 to 30 months of treatment ( 9 out of 24 , 37.5 % ) . The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients . Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction", "BACKGROUND Panic disorder ( PD ) is generally regarded as a chronic condition with considerable variation in severity of symptoms . AIMS To describe the long-term outcome of naturalistically treated PD . METHODS Fifty-five out patients with PD , who participated in a placebo-controlled drug trial of the efficacy of alprazolam and imipramine 15 years ago were reassessed with the same instruments used in the original study . RESULTS Complete recovery ( no panic attacks and no longer on medication during the last 10 years ) was seen in 18 % of patients , and an additional 13 % recovered but were still on medication . Fifty-one percent experienced recurrent anxiety attacks whereas 18 % still met diagnostic criteria for PD . The incidence of agoraphobia decreased from 69 % to 20 % . Patients with agoraphobia at admission tended to have a poorer long-term outcome according to daily functioning compared with patients without agoraphobia at admission , although both groups reported improved daily functioning at follow-up . Maintenance medication was common . No benzodiazepine abuse was reported . CONCLUSION PD has a favourable outcome in a substantial proportion of patients . However , the illness is chronic and needs treatment . The short-term treatment given in the drug trial had no influence on the long-term outcome", "Objective : Generalized anxiety disorder ( GAD ) is common in older adults and can be treated with selective serotonin reuptake inhibitors ( SSRIs ) . Genetic variation in the serotonin transporter gene promoter region is posited to be associated with SSRI efficacy : 2 polymorphisms ( 5-HTTLPR S/L and rs25531 g/a ) form a haplotype with the La combination having higher transcription activity than other haplotypes . We hypothesized that GAD patients with no La haplotypes ( La− ) have lower SSRI treatment efficacy than those with 1 to 2 La haplotypes ( La+ ) . Method : The study enrolled subjects aged 60 years or older with a principal diagnosis of GAD into a 12-week , r and omized trial of escitalopram versus placebo . One hundred fifty subjects were genotyped for the serotonin transporter promoter region haplotype and were divided into La− and La+ genotype groups ; the primary analyses were done in European Americans only ( n = 125 ; n = 59 with escitalopram and n = 66 with placebo ) . Results : Escitalopram had no efficacy in the La− group versus moderate efficacy in the La+ group . This genetic moderation of SSRI efficacy was due to a higher placebo response in La− subjects , compared with La+ subjects . Drug concentration did not affect the genetic results . Exploratory analyses suggest that La− subjects had greater variability of anxiety symptoms unrelated to treatment . Conclusions : The serotonin transporter promoter haplotype is associated with variability in SSRI efficacy for late-life GAD . The variability may result from a genetic effect on anxiety symptom variability unrelated to treatment , rather than a pharmacodynamic effect that has been previously assumed . Further research is needed to underst and the pharmacogenetic mechanism of this haplotype", "Antidepressant drugs are the preferred choice for the treatment of generalized anxiety disorder ( GAD ) . However , the choice of pharmacotherapy is determined on a trial- and -error basis , as the underlying mechanisms of treatment response are unknown . We examined whether the COMT gene , which has been known to play a role in antidepressant treatment response in major depressive disorder ( MDD ) , has a pharmacogenetic effect in antidepressant treatment response in GAD . In our study , 156 patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study . Genotypes were obtained for the COMT functional variant rs4680 ( Val158Met ) for all patients ; however , pharmacogenetic analysis was only conducted for the European American population ( n=112 ) . We found no significant association between our primary Hamilton Anxiety Scale outcome measure and rs4680 . However , we did find a nominally significant allelic association between this variant and a secondary treatment outcome measure ( CGI-I ) in our European American population ( n=112 ) . Furthermore , we show a slight dominant effect of the A-allele with the CGI-I measure in the European American population indicating a possible pharmacogenetic role of rs4680 in antidepressant treatment outcome in GAD . Further studies in a larger population are needed to confirm this effect", "Hendriks G‐J , Keijsers GPJ , Kampman M , Oude Voshaar RC , Verbraak MJPM , Broekman TG , Hoogduin CAL . A r and omized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder", "Abstract Objective : Short-term clinical trials have demonstrated the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder ( GAD ) . This study examined long-term safety and tolerability of pregabalin in patients with GAD , social anxiety disorder ( SAD ) , or panic disorder ( PD ) . Research design and methods : Patients ( n = 528 ) completing one of four r and omized , double-blind , placebo-controlled trials of pregabalin for GAD , SAD , or PD were treated , open label , with flexible-dose pregabalin ( 150–600 mg/day ) for 1 year . Clinical trial registration : NCT00150449 . Main outcome measures : The primary outcomes were safety and tolerability . Illness severity was assessed at baseline and Weeks 27/52 using the Clinical Global Impression of Severity ( CGI-S ) scale . Patients were characterized as ‘ responders ’ or ‘ non-responders ’ based on CGI-S scores ≤2 and > 2 , respectively . Analyses were performed on the total anxiety ( GAD , SAD and PD ) and GAD groups . Results : During 1 year of treatment with pregabalin , dizziness ( 12.5 % ) was the only treatment-related adverse event ( AE ) occurring ≥10 % . Somnolence , weight gain , headache and insomnia occurred at 7.6 % , 5.5 % , 5.3 % and 4.7 % , respectively . Few treatment-related AEs were rated as severe in the total anxiety ( 5.1 % ) or GAD ( 3.6 % ) groups . Discontinuation rates due to AEs were similar ( 9.7 % and 10.6 % , respectively ) . No clinical ly significant laboratory , electrocardiogram , or other treatment-related safety findings were noted , except for treatment-related weight gain , which occurred in both the total ( 24.4 % ) and GAD ( 19.4 % ) groups . Mean CGI-S scores were similar at baseline in the total ( n = 528 ; score , 3.4 ) and GAD groups ( n = 330 ; score , 3.6 ) , and CGI-S responder rates were similar at last-observation-carried-forward endpoint ( 51.3 % and 48.1 % , respectively ) . Conclusions : Pregabalin was generally well tolerated in the long-term treatment of anxiety disorders . Improvement in illness severity was maintained over time . The key limitations of this study were that it was not r and omized and neither placebo- nor active-comparator-controlled", "Objectives : Selective serotonin reuptake inhibitors ( SSRIs ) are currently considered as the first drug of choice in the treatment of panic disorder ( PD ) . The aim of this long-term , naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD . Outcome measures included relapse rates and adverse effects . Methods : Two hundred patients with PD were enrolled in our study . All subjects met DSM-IV criteria for PD or PD with agoraphobia ( PDA ) . All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram ( n = 50 ) , fluoxetine ( n = 50 ) , fluvoxamine ( n = 50 ) , or paroxetine ( n = 50 ) in a r and omized , nonblinded fashion . Both the treating psychiatrist and the patients were not blind to the assigned treatment , but the clinician raters were blind to the study medication . The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists . The Panic Self- Question naire , which is a self-report scale , was administered at baseline and then once per month during the duration of the 12-month study . The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study . Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits . The body weight of study subjects was measured at baseline , and then at the 12th month visit end point . Results : Of 200 patients who entered the study , 127 patients ( 63.5 % ) completed the full 12-month protocol . Retention rates were highest for paroxetine ( 76 % [ 38/50 ] ) , intermediate for citalopram ( 68 % [ 34/50 ] ) and fluvoxamine ( 60 % [ 30/50 ] ) , and lowest for fluoxetine ( 50 % [ 25/50 ] ) . Patients who completed the 12-month protocol responded favorably to the study treatment . The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8 . At visits on months 3 , 6 , 9 , and 12 , however , there were no statistically significant differences between the 4 groups in relapse rates ( defined as the occurrence of 1 or more panic attacks during the previous week of treatment ) ( F1,127 = 0.17 ; P = 0.13 [ not statistically significant ] ) . At the 12th month end point , patients in all 4 treatment groups had a statistically significant increase in body weight . Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment . Reports of sexual adverse effects at the 12th month visit were similar in the citalopram , fluoxetine , and paroxetine groups , but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit . Conclusions : Most of our PD patients responded well to 12-month treatment with either citalopram , fluoxetine , fluvoxamine , or paroxetine , and the overall response rate was equal after the first 4 weeks of treatment . Although patients treated with paroxetine had the lowest dropout rates during the initiation phase , they had the highest rate of adverse effects as measured at the 12th month visit . Conversely , patients in the fluvoxamine group had the highest dropout rate ( which was primarily caused by adverse effects in the initiation phase of treatment . ) ; however , patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents . Overall , when measured at the 12th month visit , monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine . In addition , monotherapy with paroxetine , citalopram , and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine", "BACKGROUND This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD . METHODS Analysis of patient-reported data from a r and omized-withdrawal , double-blind , placebo-controlled study of quetiapine XR monotherapy in GAD . Following open-label run-in ( 4 - 8 weeks ) and a 12 - 18-week stabilization phase ( quetiapine XR 50 , 150 , or 300 mg/day ) , eligible patients were r and omized to continue on quetiapine XR or receive placebo for up to 52 weeks . Primary variable was time to an anxiety event . Secondary variables included the Sheehan Disability Scale ( SDS ) and Pittsburgh Sleep Quality Index ( PSQI ) . RESULTS In total , 432 patients were r and omized ( quetiapine XR , N=216 ; placebo , N=216 ) . The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo ( HR 0.19 ; 95 % CI 0.12 , 0.31 ; p Quetiapine XR was more effective than placebo at maintaining SDS total scores ( LSM change : -0.19 vs. 1.01 ; p=0.017 ) and non-work-related SDS domain score ' family life/home responsibilities ' ( -0.13 vs. 0.32 ; p=0.011 ) , but not ' social life ' ( 0.05 vs. 0.34 ; p=0.114 ) . Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ' days lost ' ( -0.05 vs. 0.11 ; p=0.027 ) , but not ' work/school ' ( -0.10 vs. 0.29 ; p=0.051 ) or ' days underproductive ' ( 0.06 vs. 0.13 ; p=0.619 ) . PSQI global scores were reduced from r and omization with quetiapine XR vs. placebo ( 0.39 vs. 1.60 ; p patients with GAD , long-term treatment with quetiapine XR ( 50 - 300 mg/day ) monotherapy was effective at maintaining improvements in functioning and sleep quality", "BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs", "OBJECTIVE Generalized anxiety disorder is common among older adults and leads to diminished health and cognitive functioning . Although antidepressant medications are efficacious , many elderly individuals require augmentation treatment . Furthermore , little is known about maintenance strategies for older people . The authors examined whether sequenced treatment combining pharmacotherapy and cognitive-behavioral therapy ( CBT ) boosts response and prevents relapse in older adults with generalized anxiety disorder . METHOD Participants were individuals at least 60 years of age with generalized anxiety disorder ( N=73 ) who were recruited from outpatient clinics at three sites . Participants received 12 weeks of open-label escitalopram and were then r and omly assigned to one of four conditions : 16 weeks of escitalopram ( 10 - 20 mg/day ) plus modular CBT , followed by 28 weeks of maintenance escitalopram ; escitalopram alone , followed by maintenance escitalopram ; escitalopram plus CBT , followed by pill placebo ; and escitalopram alone , followed by placebo . RESULTS Escitalopram augmented with CBT increased response rates on the Penn State Worry Question naire but not on the Hamilton Anxiety Rating Scale compared with escitalopram alone . Both escitalopram and CBT prevented relapse compared with placebo . CONCLUSIONS This study demonstrates effective strategies for treatment of generalized anxiety disorder in older adults . The sequence of antidepressant medication augmented with CBT leads to worry reduction in the short-term . Continued medication prevents relapse , but for many individuals , CBT would allow sustained remission without requiring long-term pharmacotherapy", "High-potency benzodiazepines , such as clonazepam , are frequently used in the treatment of panic disorder ( PD ) because of their rapid onset of action and good tolerability . However , there is concern about their potential to cause withdrawal symptoms . We aim ed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years . A specific scale for judging withdrawal was also developed , the Composite Benzodiazepine Discontinuation Symptom Scale . We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication . The trial consisted of a 4-month period of tapering and an 8-month follow-up period . The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached , followed by a decrease of 0.25 mg per week . The mean dosage at the start of tapering was 2.7 ± 1.2 mg/d . In total , 51 ( 68.9 % ) of the patients were free of the medication after the 4 months of tapering according to the protocol , and 19 ( 26.0 % ) of the patients needed another 3 months to be free of medication . Clonazepam discontinuation symptoms were mostly mild and included mainly : anxiety , shaking/trembling/tremor , nausea/vomiting , insomnia/nightmares , excessive sweating , tachycardia/palpitations , headache , weakness , and muscle aches . The improvement in PD and general well-being was maintained during both the taper and follow-up phases . Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually . We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk" ]

[ "Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation ( AF ) . We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation . Methods and results Patients r and omized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) trial ( n = 14 264 ) were grouped by baseline AF category : paroxysmal or persistent . Multivariable adjustment was performed to compare thrombo-embolic events , bleeding , and death between groups , in high-risk subgroups , and across treatment assignment ( rivaroxaban or warfarin ) . Of 14 062 patients , 11 548 ( 82 % ) had persistent AF and 2514 ( 18 % ) had paroxysmal AF . Patients with persistent AF were marginally older ( 73 vs. 72 , P = 0.03 ) , less likely female ( 39 vs. 45 % , P patients with paroxysmal AF . In patients r and omized to warfarin , time in therapeutic range was similar ( 58 vs. 57 % , P = 0.94 ) . Patients with persistent AF had higher adjusted rates of stroke or systemic embolism ( 2.18 vs. 1.73 events per 100-patient-years , P = 0.048 ) and all-cause mortality ( 4.78 vs. 3.52 , P = 0.006 ) . Rates of major bleeding were similar ( 3.55 vs. 3.31 , P = 0.77 ) . Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment ( rivaroxaban vs. warfarin , Pinteraction = 0.6 ) . Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation , those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF", "Background and Purpose — We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation ( AF ) , identify the main factors associated with early death , and assess the effect of treatment with different doses of subcutaneous unfractionated heparin ( UFH ) given within 48 hours . Methods — We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial , first for all treatment groups combined . Then , among patients with AF , we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset . Results — A total of 3169 patients ( 17 % ) had AF . Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID , 773 to UFH 5000 IU SC BID , and 1612 to no heparin . Within each of these groups , half of the patients were r and omly assigned to aspirin 300 mg once daily . Compared with patients without AF , patients with AF were more likely to be female ( 56 % versus 45 % ) , to be old ( mean age , 78 versus 71 years ) , to have an infa rct on prer and omization CT ( 57 % versus 47 % ) , and to have impaired consciousness ( 37 % versus 20 % ) . The initial ischemic stroke type was more often a large-artery infa rct ( 36 % versus 21 % ) . A lacunar stroke syndrome was less common ( 13 % versus 26 % ) . Death within 14 days was more common in patients with AF ( 17 % versus 8 % ) and more often attributed to neurological damage from the initial stroke ( 10 % versus 4 % ) . The frequency of recurrent ischemic or undefined stroke was not significantly different ( 3.9 % versus 3.3 % ) . The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU ( n=784 ) , UFH 5000 IU ( n=773 ) , and to no-heparin ( n=1612 ) groups were as follows : ischemic stroke , 2.3 % , 3.4 % , 4.9 % ( P = 0.001 ) ; hemorrhagic stroke , 2.8 % , 1.3 % , 0.4 % ( P any stroke or death , 18.8 % , 19.4 % and 20.7 % ( P = 0.3 ) , respectively . No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent . Conclusions — Acute ischemic stroke patients with AF have a higher risk of early death , which can be explained by older age and larger infa rcts but not by a higher risk of early recurrent ischemic stroke , although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type ( 1.3 % versus 0.9 % ) . In patients with AF the absolute risk of early recurrent stroke is low , and there is no net advantage to treatment with heparin . These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF", "BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in the Framingham Heart Study . METHODS We review ed and adjudicated electrocardiograms ( ECGs ) previously classified as flutter or AF/flutter and another 100 ECGs r and omly selected from AF cases . We examined the clinical correlates of flutter by matching up to 5 AF and 5 referents to each flutter case using a nested case referent design . We determined the 10-year outcomes associated with flutter with Cox models . RESULTS During mean follow-up of 33.0 ± 12.2 years , 112 participants ( mean age 72 ± 10 years , 30 % women ) developed flutter . In multivariable analyses , smoking ( odds ratio [ OR ] 2.84 , 95 % confidence interval [ CI ] 1.54 - 5.23 ) , increased PR interval ( OR 1.28 per SD , 95 % CI 1.03 - 1.60 ) , myocardial infa rct ion ( OR 2.25 , 95 % CI 1.05 - 4.80 ) and heart failure ( OR 5.22 , 95 % CI 1.26 - 21.64 ) were associated with incident flutter . In age- and sex-adjusted models , flutter ( vs referents ) was associated with 10-year increased risk of AF ( hazard ratio [ HR ] 5.01 , 95 % CI 3.14 - 7.99 ) , myocardial infa rct ion ( HR 3.05 , 95 % CI 1.42 - 6.59 ) , heart failure ( HR 4.14 , 95 % CI 1.90 - 8.99 ) , stroke ( HR 2.17 , 95 % CI 1.13 - 4.17 ) , and mortality ( HR 2.00 , 95 % CI 1.44 - 2.79 ) . CONCLUSION We identified the clinical correlates associated with flutter and observed that flutter was associated with multiple adverse outcomes ", "Background — Atrial fibrillation is associated with increased mortality , but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy . Methods and Results — The R and omized Evaluation of Long-Term Anticoagulant Therapy ( RE-LY ) trial r and omized 18 113 patients ( age , 71.5±9 years ; male , 64 % ; CHADS2 score , 2.1±1 ) to receive dabigatran or warfarin . Median follow-up was 2 years , and complete follow-up was achieved in 99.9 % of patients . All deaths were categorized by the investigators using prespecified definitions followed by central adjudication . Overall , 1371 deaths occurred ( annual mortality rate , 3.84 % ; 95 % confidence interval [ CI ] , 3.64–4.05 ) . Cardiac deaths ( sudden cardiac death and progressive heart failure ) accounted for 37.4 % of all deaths , whereas stroke- and hemorrhage-related deaths represented 9.8 % of the total mortality . An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular ( embolism and hemorrhage-related ) mortality ( relative risk , 0.63 ; 95 % CI , 0.45–0.88 ; P=0.007 ) , whereas other causes of death were similar between treatments , including cardiac mortality ( relative risk , 0.96 ; 95 % CI , 0.80–1.15 ; P=0.638 ) . The two strongest independent predictors of cardiac death in this population were heart failure ( hazard ratio , 3.02 ; 95 % CI , 2.45–3.73 ; P and prior myocardial infa rct ion ( hazard ratio , 2.05 ; 95 % CI , 1.61–2.62 ; P of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population . These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00262600", "Background — There is a modest risk of myocardial infa rct ion ( MI ) and myocardial ischemic events in patients with atrial fibrillation . Methods and Results — Data from the RE-LY study ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) were used to report rates of MI , unstable angina , cardiac arrest , and cardiac death and the prespecified net clinical benefit and treatment effects of dabigatran versus warfarin . MI occurred at annual rates of 0.82 % and 0.81 % with dabigatran 110 or 150 mg BID compared with 0.64 % with warfarin ( hazard ratio [ HR ] 1.29 , 95 % confidence interval [ CI ] 0.96–1.75 , P=0.09 for dabigatran 110 mg ; HR 1.27 , 95 % CI 0.94–1.71 , P=0.12 for dabigatran 150 mg ) . Annual rates of a composite of MI , unstable angina , cardiac arrest , and cardiac death were 3.16 % per year with dabigatran 110 mg , 3.33 % per year with dabigatran 150 mg , and 3.41 % per year with warfarin ( HR versus warfarin 0.93 , 95 % CI 0.80–1.06 , P=0.28 for dabigatran 110 mg and HR 0.98 , 95 % CI 0.85–1.12 , P=0.77 for dabigatran 150 mg ) . Events prespecified as “ net clinical benefit ” ( all strokes , systemic embolism , MI , pulmonary embolism , major bleeding , and all-cause death ) occurred at a rate of 7.34 % per year with dabigatran 110 mg , 7.11 % per year with dabigatran 150 mg , and 7.91 % per year with warfarin ( HR 0.92 , 95 % CI 0.84–1.01 , P=0.09 for dabigatran 110 mg and HR 0.90 , 95 % CI 0.82–0.99 , P=0.02 for dabigatran 150 mg ) . The relative effects of dabigatran versus warfarin on myocardial ischemic events were consistent in patients with or without a baseline history of MI or coronary artery disease . Conclusions — There was a nonsignificant increase in MI with dabigatran compared with warfarin , but other myocardial ischemic events were not increased . Treatment effects of dabigatran were consistent in patients at higher and lower risk of myocardial ischemic events . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT 00262600", "BACKGROUND AND PURPOSE Thoracic aortic plaque identified by transesophageal echocardiography heightens the risk of stroke associated with atrial fibrillation ( AF ) . We sought to identify the prevalence , predictors , and implication s of aortic plaque in patients with nonvalvular AF . METHODS Thoracic aortic plaque was prospect ively sought in 770 persons with AF with the use of transesophageal echocardiography and classified as simple or complex on the basis of thickness > /=4 mm , ulceration , or mobility . Clinical and echocardiographic features of thromboembolism were correlated by multivariate analysis . RESULTS Aortic plaque was detected in 57 % of the cohort , and complex plaque was detected in 25 % . Both were found more frequently in the descending than in the proximal aorta . Potentially etiologic patient characteristics independently associated with complex plaque included advanced age , history of hypertension , diabetes , and past or present tobacco use . Comorbidities associated with aortic plaque were prior thromboembolism , increased pulse pressure , ischemic heart disease , stenosis or sclerosis of the aortic valve , mitral annular calcification ( > 10 % ) , elevated serum creatinine concentration , spontaneous echo contrast in the left atrium or appendage , and left atrial appendage thrombus . The prevalence of complex plaque in patients aged pulse pressure > /=65 mm Hg was 4 % ( 95 % CI , 1 % to 6 % ) . CONCLUSIONS Aortic plaque is prevalent in patients with AF and is associated with atherosclerosis risk factors and with left atrial stasis or thrombosis , which are themselves independent stroke risk factors . Since the predominant location of complex plaque was in the descending aorta , the role of aortic plaque as a source of embolism in AF is uncertain", "IMPORTANCE Myocardial infa rct ion ( MI ) is an established risk factor for atrial fibrillation ( AF ) . However , the extent to which AF is a risk factor for MI has not been investigated . OBJECTIVE To examine the risk of incident MI associated with AF . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort of 23,928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) cohort between 2003 and 2007 , with follow-up through December 2009 . MAIN OUTCOMES AND MEASURES Expert-adjudicated total MI events ( fatal and nonfatal ) . RESULTS Over 6.9 years of follow-up ( median 4.5 years ) , 648 incident MI events occurred . In a sociodemographic-adjusted model , AF was associated with about 2-fold increased risk of MI ( hazard ratio [ HR ] , 1.96 [ 95 % CI , 1.52 - 2.52 ] ) . This association remained significant ( HR , 1.70 [ 95 % CI , 1.26 - 2.30 ] ) after further adjustment for total cholesterol , high-density lipoprotein cholesterol , smoking status , systolic blood pressure , blood pressure-lowering drugs , body mass index , diabetes , warfarin use , aspirin use , statin use , history of stroke and vascular disease , estimated glomerular filtration rate , albumin to creatinine ratio , and C-reactive protein level . In subgroup analysis , the risk of MI associated with AF was significantly higher in women ( HR , 2.16 [ 95 % CI , 1.41 - 3.31 ] ) than in men ( HR , 1.39 [ 95 % CI , 0.91 - 2.10 ] ) and in blacks ( HR , 2.53 [ 95 % CI , 1.67 - 3.86 ] ) than in whites ( HR , 1.26 [ 95 % CI , 0.83 - 1.93 ] ) ; for interactions , P = .03 and P = .02 , respectively . On the other h and , there were no significant differences in the risk of MI associated with AF in older ( ≥75 years ) vs younger ( increased risk of incident MI , especially in women and blacks . These findings add to the growing concerns of the seriousness of AF as a public health burden : in addition to being a well-known risk factor for stroke , AF is also associated with increased risk of MI", "OBJECTIVES The aim of this study was to determine the independent hemodynamic effects of an irregular sequence of ventricular cycle lengths in patients with atrial fibrillation ( AF ) . BACKGROUND Atrial fibrillation may reduce cardiac output by several possible mechanisms , including loss of the atrial contribution to left ventricular filling , valvular regurgitation , increased ventricular rate or irregular RR intervals . This study was design ed to evaluate the effects of an irregular RR interval , independent of the average ventricular rate , on cardiac hemodynamic data during AF . METHODS Sixteen patients with AF were studied invasively . During intrinsically conducted AF ( mean rate 102 + /- 22 beats/ min ) , the right ventricular apex electrogram was recorded onto frequency-modulated ( FM ) tape . After atrioventricular node ablation , the right ventricular apex was stimulated in three pacing modes in r and omized sequence : 1 ) VVI at 60 beats/min ; 2 ) VVI at the same average rate as during intrinsically conducted AF ( 102 + /- 22 beats/min ) ; and 3 ) during VVT pacing in which the pacemaker was triggered by playback of the FM tape recording of the right ventricular apex electrogram previously recorded during intrinsically conducted AF ( VVT 102 + /- 22 beats/min ) . RESULTS Compared with VVI pacing at the same average rate , an irregular sequence of RR intervals decreased cardiac output ( 4.4 + /- 1.6 vs. 5.2 + /- 2.4 liters/min , p pulmonary capillary wedge pressure ( 17 + /- 7 vs. 14 + /- 6 mm Hg , p right atrial pressure ( 10 + /- 6 vs. 8 + /- 4 mm Hg , p hemodynamic consequences that are independent of heart rate", "Background and Purpose — In national guidelines , absolute long-term risk of myocardial infa rct ion ( MI ) or coronary death determines target low-density lipoprotein levels , but stroke patients are not explicitly addressed . We determined the absolute 5-year risk of cardiovascular outcomes and their predictors after first ischemic stroke in a multiethnic cohort . Methods — A population -based cohort of first ischemic stroke patients ≥40 years old was prospect ively followed annually for recurrent stroke , MI and cause-specific mortality . Kaplan-Meier 5-year risks for MI or vascular death ( primary outcome ) , and other cardiovascular events , were calculated . Univariate and multivariate Cox proportional hazards models were used to calculate hazard ratios and 95 % CI for predictors of cardiovascular outcomes . Results — Mean age ( n=655 ) was 69.7±12.7 years ; 55.4 % of participants were women , and 51.3 % Hispanic . The 5-year risk of MI or vascular death was 17.4 % ( 95 % CI , 14.2 % to 20.6 % ) . Independent historical predictors of MI or vascular death were age > 70 years ( hazard ratio 1.62 , 1.07 to 2.44 ) , history of coronary artery disease ( hazard ratio 1.76 , 1.13 to 2.74 ) , and atrial fibrillation ( hazard ratio 1.76 , 1.05 to 2.94 ) . In the lowest risk group , those ≤70 years old without coronary artery disease , 5-year risk of MI or vascular death was 9.7 % . Conclusions — The absolute risk of MI or vascular death after ischemic stroke , even in those without high-risk features , approximates levels used by national organizations to design ate groups of patients at high risk of vascular events . The comparability of levels of absolute risk among stroke and cardiac patients may have treatment implication", "OBJECTIVE In healthy persons , cardiovascular risk is the result of multiple interacting risk associates including demographic , clinical , genetic and environmental factors . Several non-invasive tools such as echocardiography , ultrasonography and electrocardiography as well as new biochemical markers were shown to be applicable to predict cardiovascular events . However , implementation of all of these tools has not been tested before . The aim of the study was to evaluate the independent predictors of major adverse cardiovascular events in a prospect i ve population based study , with the use of bioempedance analysis , echocardiography , ultrasonography and ECG . PATIENTS AND METHODS The baseline measurements were conducted on 2230 participants ( 1427 women , 803 men with a mean age of 49 ± 15 ) . The follow-up was done 36 months after the baseline admission via telephone call . Major adverse event was defined as mortality or myocardial infa rct ion or stroke . RESULTS Follow-up data was possible in 1495 participants ( 65 % ) . During the follow-up of 36 months ( 4485 patient years ) , 42 major adverse events occurred ( 0.03 % ) . Among them , 16 were death ( 1 stroke , 2 cancer , 13 cardiac related ) , 12 were stroke and 14 were myocardial infa rct ion . Age , body mass index and atrial fibrillation were independent predictors of major adverse events ; AF being the most powerful ( Odds ratio 10.46 ; 95 % confidence interval [ 1.73 - 63.14 ] ; p = 0.010 ) . CONCLUSIONS Age , lower body mass index and atrial fibrillation were independent predictors of major cardiovascular events in our cohort", "BACKGROUND The risk of acute myocardial infa rct ion ( AMI ) in patients with atrial fibrillation ( AF ) with a CHA2DS2-VASc score of 0 ( for men ) or 1 ( for women ) has not been previously investigated . OBJECTIVE The objective of the present study was to compare the risk of AMI in AF and non-AF subjects with a low ( 0 or 1 ) CHA2DS2-VASc score . METHODS By using the National Health Insurance Research Data base in Taiwan , we identified 7254 men with AF ( with a CHA2DS2-VASc score of 0 ) and 4860 women with AF ( with a CHA2DS2-VASc score of 1 ) . For each study patient , 1 age- , sex- , and CHA2DS2-VASc score-matched subject without AF was r and omly selected to constitute the control group ( n = 12,114 ) . The clinical end point was the occurrence of AMI . RESULTS During a mean follow-up period of 5.7 ± 3.6 years , 258 patients ( 1.1 % ) suffered an AMI , with an annual incidence of 0.29 % and 0.10 % for patients with and without AF . AF was an independent risk factor of AMI , with an adjusted hazard ratio ( HR ) of 2.93 ( 95 % confidence interval 2.21 - 3.87 ; P .001 ) . The risk of AMI was higher in men with AF than in women with AF , with a hazard ratio of 2.24 ( 95 % confidence interval 1.61 - 3.11 ; P patients with a CHA2DS2-VASc score of 0 or 1 , AF was an independent risk factor of AMI . The risk of AMI was higher in men with AF than in women with AF . Cardiovascular risk prevention should be performed as part of the holistic management of AF to minimize the risks of AMI associated with AF", "Prospect i ve data from Busselton , Western Australia , collected during triennial surveys from 1966 - 81 with follow-up of subjects to 1983 , showed that atrial fibrillation ( AF ) was frequent in elderly people and associated with increased mortality . Of 1770 people aged over 60 years , 40 were in atrial fibrillation when first seen and a further 47 developed it during follow-up . Atrial fibrillation was positively associated with angina , history of a myocardial infa rct ion and left bundle branch block . Relative mortality in those with atrial fibrillation compared with those without it , was 1.92 for all causes , 1.82 for death from cardiovascular causes ( excluding stroke ) and 3.78 for deaths from stroke , after adjustment by proportional hazards regression for confounding effects of age , sex , history of a myocardial infa rct ion , an abnormal electrocardiogram , angina , cholesterol level systolic blood pressure and Quetelet 's Index ( weight/height2 ) . The excess relative mortality declined with increasing age for both women and men . This raised relative mortality remained constant with time from the first detection of AF for all causes and cardiovascular causes but appeared to increase with time from detection for stroke death . The risk of death from stroke was greatest in the younger women . The observed risk of death from stroke in patients with AF suggests that anticoagulant use should be considered in selected patients", "OBJECTIVE This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and , if so , whether the increase could be attributed to progressive heart failure or arrhythmic death . BACKGROUND Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias . The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure . METHODS A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality , progressive pump-failure death and arrhythmic death . RESULTS The patients with atrial fibrillation at baseline , compared to those in sinus rhythm , had greater all-cause mortality ( 34 % vs. 23 % , p death attributed to pump-failure ( 16.7 % vs. 9.4 % , p end point of death or hospitalization for heart failure ( 45 % vs. 33 % , p arrhythmic deaths . After multivariate analysis , atrial fibrillation remained significantly associated with all-cause mortality ( relative risk [ RR ] 1.34 , 95 % confidence interval [ CI ] 1.12 to 1.62 , p=0.002 ) , progressive pump-failure death ( RR 1.42 , 95 % CI 1.09 to 1.85 , p=0.01 ) , the composite end point of death or hospitalization for heart failure ( RR 1.26 , 95 % CI 1.03 to 1.42 , p=0.02 ) , but not arrhythmic death ( RR 1.13 ; 95 % CI 0.75 to 1.71 ; p=0.55 ) . CONCLUSIONS The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality , largely explained by an increased risk for pump-failure death . These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction", "BACKGROUND Recent findings suggest that patients with atrial fibrillation ( AF ) , in addition being at thromboembolic risk , are at risk of myocardial infa rct ion ( MI ) . Our aim was to investigate predictors of MI and cardiovascular death in a cohort of patients with AF who were taking anticoagulants . METHODS We prospect ively followed up 1,019 patients with AF for a median of 33.7 months ( 3,223 person-years ) . All patients were treated with oral vitamin K antagonists . Primary outcome was a composite end point of cardiovascular events ( CVEs ) including fatal/nonfatal MI , cardiac revascularization , and cardiovascular death . RESULTS The mean age of the patients was 73.2 years , and 43.8 % were women . At follow-up , 111 CVEs ( 3.43%/y ) had occurred : 47 fatal-nonfatal MI/revascularization and 64 cardiovascular deaths . In addition , 31 stroke/transient ischemic attacks ( 0.96%/y ) were recorded . Patients experiencing CVEs were older ( P metabolic syndrome ( MetS ) ( P = .005 ) , heart failure ( P = .001 ) , and prior cardiac ( P cerebrovascular events ( P smoking ( HR , 2.158 ; 95 % CI , 1.193 - 3.901 ; P = .011 ) , history of cerebrovascular ( HR , 1.704 ; 95 % CI , 1.119 - 2.597 ; P = .013 ) and cardiac ( HR , 1.658 ; 95 % CI , 1.105 - 2.489 ; P = .015 ) events , MetS ( HR , 1.663 ; 95 % CI , 1.107 - 2.499 ; P = .014 ) , heart failure ( HR , 1.584 ; 95 % CI , 1.021 - 2.456 ; P = .040 ) , and male sex ( HR , 1.499 ; 95 % CI , 1.010 - 2.223 ; P = .044 ) predicted CVEs . CONCLUSIONS Patients with AF still experience a high rate of CVEs despite receiving anticoagulant treatment . MetS is a common clinical feature in patients with AF , which increases the risk of CVEs . A holistic approach is needed to reduce the cardiovascular risk in patients with AF . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01882114 ; URL : www . clinical trials.gov", "CONTEXT The risks associated with new-onset atrial fibrillation ( AF ) among middle-aged women and population s with a low comorbidity burden are poorly defined . OBJECTIVES To examine the association between incident AF and mortality in initially healthy women and to evaluate the influence of associated cardiovascular comorbidities on risk . DESIGN , SETTING , AND PARTICIPANTS Between 1993 and March 16 , 2010 , 34,722 women participating in the Women 's Health Study underwent prospect i ve follow-up . Participants were 95 % white , older than 45 years ( median , 53 [ interquartile range { IQR } , 49 - 59 ] years ) , and free of AF and cardiovascular disease at baseline . Cox proportional hazards models with time-varying covariates were used to determine the risk of events among women with incident AF . Secondary analyses were performed among women with paroxysmal AF . MAIN OUTCOME MEASURES Primary outcomes included all-cause , cardiovascular , and noncardiovascular mortality . Secondary outcomes included stroke , congestive heart failure , and myocardial infa rct ion . RESULTS During a median follow-up of 15.4 ( IQR , 14.7 - 15.8 ) years , 1011 women developed AF . Incidence rates per 1000 person-years among women with and without AF were 10.8 ( 95 % confidence interval [ CI ] , 8.1 - 13.5 ) and 3.1 ( 95 % CI , 2.9 - 3.2 ) for all-cause mortality , 4.3 ( 95 % CI , 2.6 - 6.0 ) and 0.57 ( 95 % CI , 0.5 - 0.6 ) for cardiovascular mortality , and 6.5 ( 95 % CI , 4.4 - 8.6 ) and 2.5 ( 95 % CI , 2.4 - 2.6 ) for noncardiovascular mortality , respectively . In multivariable models , hazard ratios ( HRs ) of new-onset AF for all-cause , cardiovascular , and noncardiovascular mortality were 2.14 ( 95 % CI , 1.64 - 2.77 ) , 4.18 ( 95 % CI , 2.69 - 6.51 ) , and 1.66 ( 95 % CI , 1.19 - 2.30 ) , respectively . Adjustment for nonfatal cardiovascular events potentially on the causal pathway to death attenuated these risks , but incident AF remained associated with all mortality components ( all-cause : HR , 1.70 [ 95 % CI , 1.30 - 2.22 ] ; cardiovascular : HR , 2.57 [ 95 % CI , 1.63 - 4.07 ] ; and noncardiovascular : HR , 1.42 [ 95 % CI , 1.02 - 1.98 ] ) . Among women with paroxysmal AF ( n = 656 ) , the increase in mortality risk was limited to cardiovascular causes ( HR , 2.94 ; 95 % CI , 1.55 - 5.59 ) . CONCLUSION Among a group of healthy women , new-onset AF was independently associated with all-cause , cardiovascular , and noncardiovascular mortality , with some of the risk potentially explained by nonfatal cardiovascular events ", "BACKGROUND Atrial fibrillation ( AF ) is a major risk factor ( RF ) for ischemic stroke . Its prevalence and prognostic impact in patients with atherothrombosis are unclear . METHODS Risk factors , drug usage , and 1-year cardiovascular ( CV ) outcomes ( CV death , myocardial infa rct ion [ MI ] , and stroke ) were compared in AF and non-AF patients from the REduction of Atherothrombosis for Continued Health ( REACH ) Registry , an international , prospect i ve cohort of 68,236 stable out patients with established atherothrombosis or > or=3 atherothrombotic RFs . RESULTS Atrial fibrillation and 1-year follow-up data are available for 63,589 patients . The prevalence of AF was , 12.5 % , 13.7 % , 11.5 % , and 6.2 % among coronary artery disease , CV disease , peripheral artery disease , and RF-only patients , respectively . Of the 6,814 patients with AF , 6.7 % experienced CV death , nonfatal MI , or nonfatal stroke within a year . The annual incidence of nonfatal stroke ( 2.4 % vs 1.6 % , P unstable angina ( 6.0 % vs 4.0 % , P CV death was more than double ( 3.2 % vs 1.4 % , P antiplatelet agents , but only 53.1 % were treated with oral anticoagulants . Even with high CHADS2 ( congestive heart failure , hypertension , aging , diabetes mellitus , and stroke ) scores , anticoagulant use did not exceed ( 59 % ) . The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients ( 1.5 % vs 0.8 % , P anticoagulants ( 53.1 % vs 7.1 % ) . CONCLUSIONS Atrial fibrillation is common in patients with atherothrombosis , associated with more frequent fatal and nonfatal CV outcomes , and underuse of oral anticoagulants", " In a r and omly selected population of 9067 individuals , 32 - 64 years of age in 1967 - 1970 , 25 ( 0.28 % ) had chronic atrial fibrillation ( CAF ) . Eight had lone atrial fibrillation . In 1984 the cases were compared with an age- and sex-matched control group of 50 and found to have more cerebrovascular accidents ( 6 versus 2 ; P less than 0.05 ) , congestive heart failure ( 9 versus 1 ; P less than 0.001 ) , and valvular rheumatic heart disease ( 3 versus 0 ) or history consistent with rheumatic fever ( 6 versus 0 ; P less than 0.01 ) . The mortality in the CAF group was 60 % higher due to an excess in cardiovascular ( relative risk 6.1 ; P less than 0.05 ) and cerebrovascular ( relative risk 12.2 ; P less than 0.05 ) causes . The prevalence or incidence of ischaemic or hypertensive heart disease or the presence of coronary risk factors did not significantly differ in the two groups . By M-mode echocardiography the left atrial size , left ventricular enddiastolic dimension and left ventricular mass were increased in the CAF patients , while the systolic left ventricular shortening was significantly less . Thus , the prevalence of CAF is low in a r and omly selected population 32 - 64 years of age and CAF is not strongly associated with ischaemic heart disease or hypertension . The CAF patients have an increased risk of dying prematurely particularly from cerebrovascular causes , even in the absence of valve disease", "OBJECTIVES The purpose of this study was to evaluate the role of congestive heart failure ( CHF ) in the association between atrial fibrillation ( AF ) and sudden cardiac death ( SCD ) . BACKGROUND Recent studies have reported the possibility of an independent association between AF and SCD . We hypothesized that a history of CHF is a significant confounder of this association . METHODS In a prospect i ve case-control analysis from the community ( The Oregon-SUDS [ Sudden Unexpected Death Study ] , 2002 to 2012 ) , SCD cases ( n = 652 ) with clinical records available ( including electrocardiography and /or echocardiography ) were compared with age- and sex-matched control patients with coronary artery disease . The association between AF and SCD was analyzed using multivariable logistic regression and propensity score matching . RESULTS Cases ( age 67.3 ± 11.7 years , 65 % male ) were more likely than control patients ( age 67.2 ± 11.4 years , 65 % male ) to have a history of AF ( p = 0.0001 ) , myocardial infa rct ion ( p = 0.007 ) , CHF ( p stroke ( p AF was a significant predictor of SCD ( odds ratio [ OR ] : 1.6 ; 95 % confidence interval [ CI ] : 1.2 to 2.0 ; p = 0.002 ) . However , in a model that included CHF , the AF-SCD association was no longer significant ( OR : 1.1 ; 95 % CI : 0.8 to 1.5 ; p = 0.45 ) , whereas CHF was a significant predictor of SCD ( OR : 3.1 ; 95 % CI : 2.4 to 4.1 ; p < 0.0001 ) . Results on the basis of propensity score matching were consistent . CONCLUSIONS Our findings suggest that a history of CHF , including both systolic and diastolic symptomatic dysfunction , may partially explain the AF-SCD association" ]

[ "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", "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", "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", "Objective To assess the efficacy of modest non-financial incentives on immunisation rates in children aged 1 - 3 and to compare it with the effect of only improving the reliability of the supply of services . Design Clustered r and omised controlled study . Setting Rural Rajasthan , India . Participants 1640 children aged 1 - 3 at end point . Interventions 134 villages were r and omised to one of three groups : a once monthly reliable immunisation camp ( intervention A ; 379 children from 30 villages ) ; a once monthly reliable immunisation camp with small incentives ( raw lentils and metal plates for completed immunisation ; intervention B ; 382 children from 30 villages ) , or control ( no intervention , 860 children in 74 villages ) . Surveys were undertaken in r and omly selected households at baseline and about 18 months after the interventions started ( end point ) . Main outcome measures Proportion of children aged 1 - 3 at the end point who were partially or fully immunised . Results Among children aged 1 - 3 in the end point survey , rates of full immunisation were 39 % ( 148/382 , 95 % confidence interval 30 % to 47 % ) for intervention B villages ( reliable immunisation with incentives ) , 18 % ( 68/379 , 11 % to 23 % ) for intervention A villages ( reliable immunisation without incentives ) , and 6 % ( 50/860 , 3 % to 9 % ) for control villages . The relative risk of complete immunisation for intervention B versus control was 6.7 ( 4.5 to 8.8 ) and for intervention B versus intervention A was 2.2 ( 1.5 to 2.8 ) . Children in areas neighbouring intervention B villages were also more likely to be fully immunised than those from areas neighbouring intervention A villages ( 1.9 , 1.1 to 2.8 ) . The average cost per immunisation was $ 28 ( 1102 rupees , about £ 16 or € 19 ) in intervention A and $ 56 ( 2202 rupees ) in intervention B. Conclusions Improving reliability of services improves immunisation rates , but the effect remains modest . Small incentives have large positive impacts on the uptake of immunisation services in re source poor areas and are more cost effective than purely improving supply . Trial registration IRSCTN87759937", "BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development", "Invasive pneumococcal disease in adults may be declining , reflecting a form of herd protection from a new pediatric pneumococcal conjugate vaccine . Our aim was to determine whether vaccination of children protects adults in the same home from bacteremic pneumococcal pneumonia . We conducted a case-control study with 43 participating hospitals across a five-county region in Pennsylvania . Eligible cases were adults with bacteremic pneumococcal pneumonia identified by the microbiology laboratories at participating hospitals . Controls were healthy adults from the region identified through r and om digit dialing . Cases and controls were interviewed by telephone . We analyzed vaccine protection in those adults who reported living in homes with at least one child 6 years of age . From April 2002 through June 2004 , there was a significant decline in the proportion of adult pneumococcal bacteremia due to any of the seven serotypes in the conjugate vaccine ( p=0.006 ) . Within this time period , 17 % of cases and controls reported living in homes with at least one child odds of bacteremic pneumococcal pneumonia among adults with children in the home ( OR=0.2 , 95 % CI 0.1 - 0.8 ) . We conclude that introduction of a pneumococcal conjugate vaccine for children has reduced the population rate of adult pneumococcal bacteremia due to vaccine serotypes and is associated with a reduced risk of bacteremic pneumococcal pneumonia for adults with children in the home", "OBJECTIVES The effectiveness of vaccines in population s must consider both direct and indirect protection . This study reanalyses data from a large individually r and omized oral cholera vaccine trial that was conducted in rural Bangladesh from 1985 to 1990 . A recent analysis of the results of that trial showed that the proportion of people in household clusters who received the vaccine was inversely related to placebo incidence during the first year of surveillance , which was attributed to herd immunity . METHODS In this study we measure the relationship between neighbourhood-level oral cholera vaccine coverage and protective efficacy ( PE ) during a 2 year follow-up period , controlling for known effect modifiers . We link trial data to a household geographic information system to facilitate the neighbourhood-level analysis . Findings Neighbourhood-level PE can be partially explained by vaccine coverage after adjusting for ecological variables . CONCLUSIONS The inverse relationship between vaccine coverage and efficacy illustrates that people living in high-coverage areas may be indirectly protected from cholera because people living around them are vaccinated", "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 )", "OBJECTIVES We evaluated the effectiveness and spillover of an after-school health education and physical activity program among Hispanic elementary school children . METHODS In fall 2008 , students in third through fifth grade s in 6 schools in El Paso , Texas ( n = 901 ) , were r and omized to intervention ( n = 292 participants ) or control ( n = 354 ) classrooms ( 4 unknown ) . Intervention classrooms also contained a spillover group ( n = 251 ) that did not join the after-school program but that completed measurements and surveys . The intervention was a 12-week culturally tailored after-school program meeting twice a week . Four-month outcomes were body mass index , aerobic capacity , and dietary intentions and knowledge . We calculated intervention exposure as the proportion of after-school participants per classroom . RESULTS Intervention exposure predicted lower body mass index ( P = .045 ) , higher aerobic capacity ( P = .012 ) , and greater intentions to eat healthy ( P = .046 ) for the classroom at follow-up . Intervention effectiveness increased with increasing proportions of intervention participants in a classroom . Non participants who had classroom contact with program participants experienced health improvements that could reduce their risk of obesity . CONCLUSIONS Spillover of beneficial intervention effects to non participants is a valuable public health benefit and should be part of program impact assessment", "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", "BACKGROUND Typhoid fever is endemic in Karachi , with an incidence among children ranging from 170 to 450 per 100,000 child-years . Vaccination strategies are important for prevention , and the Vi capsular polysaccharide ( ViCPS ) vaccine has been shown to be effective in reducing the burden of typhoid fever . METHODS A cluster r and omized trial was conducted in three low socioeconomic urban squatter settlements in Karachi , Pakistan between 2002 and 2007 . Sub sample s were followed up for assessment of immune response and adverse events after vaccination . RESULTS The study participants were similar in a wide variety of socio-demographic and economic characteristics at baseline . A total of 27,231 individuals of the total target population of 51,965 in 120 clusters either received a ViCPS vaccine ( 13,238 [ 52 % coverage ] ) or the control Hepatitis A vaccine ( 13,993 [ 53 % ] ) . Typhoid fever was diagnosed in 30 ViCPS vaccine recipients and 49 Hepatitis A vaccine recipients with an adjusted total protective effectiveness of 31 % ( 95%CI : -28 % , 63 % ) . The adjusted total vaccine protective effectiveness was -38 % ( 95%CI : -192 % , 35 % ) for children aged 2 - 5 years and 57 % ( 95%CI : 6 % , 81 % ) for children 5 - 16 years old . CONCLUSION The ViCPS vaccine did not confer statistically significant protection to children in the study areas , and there was a decline in antibody response 2 years post-vaccination . However , the ViCPS vaccine showed significant total protection in children 5 - 16 years of age , which is consistent with other studies of ViCPS vaccine conducted in India , Nepal , China and South Africa . These findings suggest that ViCPS vaccination of school-aged children will protect the children of urban , typhoid endemic areas against typhoid fever", "Highest attack rates for influenza occur in children . Immunization of schoolchildren with inactivated influenza vaccine in Michigan and Japan was associated with decreased morbidity and mortality , respectively , in older community contacts . An open-labeled , non-r and omized , community-based trial in children with the cold adapted influenza vaccine , trivalent ( CAIV-T ) was initiated to determine the coverage necessary to reduce spread of influenza in the community . Age-specific baseline rates of medically attended acute respiratory illness ( MAARI ) for Scott and White Health Plan ( SWHP ) members at intervention ( Temple and Belton ) and comparison communities ( Waco , Bryan , and College Station ) were obtained in 1997 - 1998 . During three subsequent vaccination years , 4298 , 5251 and 5150 children received one dose per season of CAIV-T. Vaccinees represented 20 - 25 % of the age-eligible children . Age-specific MAARI rates were compared for SWHP members in the intervention and comparison sites during the influenza outbreaks . Baseline age-specific MAARI rates per 100 persons for the influenza season were comparable between the intervention and comparison communities . In the subsequent three influenza seasons , the age groups 35 - 44 , 45 - 54 , 55 - 65 and > 64 years experienced reductions in MAARI rates in the intervention communities . In adults > or = 35 years of age , significant reductions in MAARI of 0.08 ( 95 % CI : 0.04 , 0.13 ) , 0.18 ( 95 % CI : 0.14 , 0.22 ) and 0.15 ( 95 % CI : 0.12 , 0.19 ) , were observed in the influenza seasons for vaccination years 1 , 2 and 3 , respectively . No consistent reduction in MAARI rates was detected in the younger age groups . Vaccination of approximately 20 - 25 % of children , 1.5 - 18 years of age in the intervention communities result ed in an indirect protection of 8 - 18 % against MAARI in adults > or = 35 years of age", "How do neighbors positively or negatively influence individuals living in rural Malawi to learn their HIV results ? Using data of location of homes and distance to neighbors , we measure the social network effects of neighbors ' learning their HIV results on individuals own learning . Using the fact that neighbors were r and omly offered monetary incentives of varying amounts to learn their HIV results , we find positive effects of neighbors attending clinics on others living nearby : a 10 percentage point increase of the percentage of neighbors ( approximately 2.4 individuals ) learning their HIV results increases the probability of learning HIV results by 1.1 percentage points . The strongest network effects are among closest neighbors ; we find no effect among religious social networks . We also find a negative interaction between direct cash incentives and peers : the effect of peers doubles among those who were not offered any individual financial incentive to learn their HIV results", "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", "OBJECTIVES To explore user perspectives on applying the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) to systematic review s of complex interventions . STUDY DESIGN AND SETTING Thirty-three authors of recent ( 2013 onward ) systematic review s were contacted regarding their perspectives on using GRADE from three Cochrane review groups : Cochrane Developmental , Psychosocial , and Learning Problems Group ; Cochrane Public Health Group ; and Cochrane Depression , Anxiety , and Neurosis Group . Framework Analysis was applied to the data to identify the challenges in applying GRADE and suggestions for its extension , that is , adaptation . These two themes were cross-compared between the groups of answers from \" simple \" vs. \" complex \" intervention review authors to identify the specific perspectives on using GRADE in review s of complex interventions . RESULTS Specific challenges were identified in applying GRADE to review s of complex interventions . These were related to the assessment of nonr and omized studies and performance bias in GRADE . Authors perceived these challenges to contribute to frequent downgrading of the \" best evidence possible \" for complex interventions . Meanwhile , GRADE was found to lack an analytic approach to enable adequate evidence synthesis and assessment of intervention implementation elements . CONCLUSION Users suggest that the GRADE guidance be extended to address-specific considerations for complex interventions", "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 Gambian infants frequently acquire Streptococcus pneumoniae soon after birth . We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine ( PCV-7 ) on pneumococcal acquisition in newborn Gambian babies . Methods Twenty-one villages were r and omised to receive PCV-7 to all subjects ( 11 vaccinated villages ) or to infants aged 2–30 months ( 10 control villages ) . Other control villagers received Meningococcal C conjugate vaccine . From 328 babies born during the trial , nasopharyngeal swabs were collected after birth , then weekly until 8 weeks of age when they received their first dose of PCV-7 . Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study . Results 57.4 % of 2245 swabs were positive for S. pneumoniae . Overall carriage was similar in both arms . In vaccinated villages fewer infants carried pneumococci of vaccine serotypes ( VT ) ( 16.9 % [ 31/184 ] vs. 37.5 % [ 54/144 ] , p pneumococci of non-vaccine serotypes ( NVT ) ( 80.9 % [ 149/184 ] vs. 75.7 % [ 109/144 ] , p = 0.246 ) . Infants from vaccinated villages had a significantly lower acquisition rate of VT ( HR 0.39 [ 0.26–0.58 ] , p and increased acquisition of NVT ( HR 1.16 [ 0.87–1.56 ] , p = 0.312 ) . VT carriage ( 51.6 % vs. 37.5 % , p = 031 in control and 46.1 % vs. 16.8 % , p villages ) and acquisition rates ( HR 0.68 [ 0.50–0.92 ] , p = 0.013 in control villages and HR 0.31 [ 0.19–0.50 ] , p baseline study . NVT carriage ( 63.2 % vs. 75.7 % , p = 0.037 in control and 67.2 % vs. 75.3 % , p = 0.005 in vaccinated villages ) and acquisition rates ( HR 1.48 [ 1.06–2.06 ] , p = 0.022 ) and ( HR 1.52 [ 1.11–2.10 ] , p = 0.010 respectively ) were significantly higher . Conclusion PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants . This indirect effect likely originated from both the child and adult vaccinated population s. Increased carriage of NVT pneumococci needs ongoing monitoring . Trial Registration IS RCT N Register", "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", "Background : Killed oral cholera vaccines are internationally licensed for older children and adults , but not for infants and young children . We investigated whether mass immunization of older children and adults can confer herd protection to children too young to be vaccinated . Methods : We analyzed the first year of surveillance of an individually r and omized , placebo-controlled trial of killed oral cholera vaccines in 89,596 older Bangladeshi children and adult women . Vaccine herd protection of children less than 2 years of age , who were too young to participate in the trial , was evaluated by determining whether the incidence of cholera during the first year of follow-up of this age group was lower in residential clusters with higher levels of vaccine coverage than in clusters with lower levels of vaccine coverage . Results : Vaccine coverage of the targeted population ranged from 4 % to 65 % in different clusters . The incidence ( cases per 1000 ) of cholera among children less than 2 years of age ranged from 18.9 in clusters in the lowest quintile of vaccine coverage to 8.6 in clusters in the highest quintile ( P = 0.004 for the inverse association between vaccine coverage and risk of cholera ) Vaccine coverage of adult women ( relative risk of cholera = 0.95 for each percent increase in vaccine coverage ; 95 % confidence interval : 0.92–0.99 ; P lower risk of cholera in children less than 2 years of age . Conclusions : Vaccination of older age groups was associated with protection of children too young to be vaccinated . The pronounced herd protection of young children associated with vaccination of adult women suggests that adult women may play a prominent role in the transmission of cholera to young children in this setting", " 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", "The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials", "Summary Background The effect of 7-valent pneumococcal conjugate vaccine ( PCV ) in developed countries was enhanced by indirect protection of unvaccinated individuals , mediated by reduced nasopharyngeal carriage of vaccine-serotype pneumococci . The potential indirect protection of 10-valent PCV ( PCV10 ) in a developing country setting is unknown . We sought to estimate the effectiveness of introduction of PCV10 in Kenya against carriage of vaccine serotypes and its effect on other bacteria . Methods PCV10 was introduced into the infant vaccination programme in Kenya in January , 2011 , accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years . We did annual cross-sectional carriage studies among an age-stratified , r and om population sample in the 2 years before and 2 years after PCV10 introduction . A nasopharyngeal rayon swab specimen was collected from each participant and was processed in accordance with WHO recommendations . Prevalence ratios of carriage before and after introduction of PCV10 were calculated by log-binomial regression . Findings About 500 individuals were enrolled each year ( total n=2031 ) . Among children younger than 5 years , the baseline ( 2009–10 ) carriage prevalence was 34 % for vaccine-serotype Streptococcus pneumoniae , 41 % for non-vaccine-serotype Streptococcus pneumoniae , and 54 % for non-typeable Haemophilus influenzae . After PCV10 introduction ( 2011–12 ) , these percentages were 13 % , 57 % , and 40 % , respectively . Adjusted prevalence ratios were 0·36 ( 95 % CI 0·26–0·51 ) , 1·37 ( 1·13–1·65 ) , and 0·62 ( 0·52–0·75 ) , respectively . Among individuals aged 5 years or older , the adjusted prevalence ratios for vaccine-serotype and non-vaccine-serotype S pneumoniae carriage were 0·34 ( 95 % CI 0·18–0·62 ) and 1·13 ( 0·92–1·38 ) , respectively . There was no change in prevalence ratio for Staphylococcus aureus ( adjusted prevalence ratio for those of PCV10 in Kilifi , carriage of vaccine serotypes was reduced by two-thirds both in children younger than 5 years and in older individuals . These findings suggest that PCV10 introduction in Africa will have substantial indirect effects on invasive pneumococcal disease . Funding GAVI Alliance and Wellcome Trust", "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 )" ]

[ "Sustained improvement in blood glucose control is the only treatment outcome which will reduce or eliminate the long term complications of diabetes mellitus . We have design ed and evaluated an electronic information system which facilitates this task . The system is voice-interactive , physician directed and affords , to remote patients , 24 h access via touch-tone telephone . Accordingly , patients access the system each day to report self-measured blood glucose levels or hypoglycaemic symptoms together with dietary changes , planned exercise , stress , illness or other lifestyle events . In turn they receive immediate advice with respect to medication dosing changes , and other pertinent feedback . Preliminary system beta-testing for safety and efficacy was performed for one year in an open study of 204 patients derived from two independent , health-care environments . Among the two testing centres , over 60,000 telephone cells were received by the computer systems during the start-up year . Safety and efficacy expectations were met . In addition , prevalence of diabetes related crises ( hyperglycaemia or hypoglycaemia ) fell approximately 3-fold . Glycated haemoglobin fell significantly ( 1.0 - 1.3 % ) in patients actively using the system . In control groups of patients not actively using the system , there were no improvements in metabolic control while body weights were stable in all groups . The new system was safe and effective in our h and s and empowered our health professionals to provide improved diabetes care", "Background Type 2 diabetes mellitus is a worldwide challenge . Practice guidelines promote structured self-monitoring of blood glucose ( SMBG ) for informing health care providers about glycemic control and providing patient feedback to increase knowledge , self-efficacy , and behavior change . Paired glucose testing — pairs of glucose results obtained before and after a meal or physical activity — is a method of structured SMBG . However , frequent access to glucose data to interpret values and recommend actions is challenging . A complete feedback loop— data collection and interpretation combined with feedback to modify treatment — has been associated with improved outcomes , yet there remains limited integration of SMBG feedback in diabetes management . Incorporating telehealth remote monitoring and asynchronous electronic health record ( EHR ) feedback from certified diabetes educators (CDEs)—specialists in glucose pattern management — employ the complete feedback loop to improve outcomes . Objective The purpose of this study was to evaluate a telehealth remote monitoring intervention using paired glucose testing and asynchronous data analysis in adults with type 2 diabetes . The primary aim was change in glycated hemoglobin (A1c)—a measure of overall glucose management — between groups after 6 months . The secondary aims were change in self-reported Summary of Diabetes Self-Care Activities ( SDSCA ) , Diabetes Empowerment Scale , and Diabetes Knowledge Test . Methods A 2-group r and omized clinical trial was conducted comparing usual care to telehealth remote monitoring with paired glucose testing and asynchronous virtual visits . Participants were aged 30 - 70 years , not using insulin with A1c levels between 7.5 % and 10.9 % ( 58 - 96 mmol/mol ) . The telehealth remote monitoring tablet computer transmitted glucose data and facilitated a complete feedback loop to educate participants , analyze actionable glucose data , and provide feedback . Data from paired glucose testing were analyzed asynchronously using computer-assisted pattern analysis and were shared with patients via the EHR weekly . CDEs called participants monthly to discuss paired glucose testing trends and treatment changes . Separate mixed-effects models were used to analyze data . Results Participants ( N=90 ) were primarily white ( 64 % , 56/87 ) , mean age 58 ( SD 11 ) years , mean body mass index 34.1 ( SD 6.7 ) kg/m2 , with diabetes for mean 8.2 ( SD 5.4 ) years , and a mean A1c of 8.3 % ( SD 1.1 ; 67 mmol/mol ) . Both groups lowered A1c with an estimated average decrease of 0.70 percentage points in usual care group and 1.11 percentage points in the treatment group with a significant difference of 0.41 percentage points at 6 months ( SE 0.08 , t159=–2.87 , P=.005 ) . Change in medication ( SE 0.21 , t157=–3.37 , P=.009 ) was significantly associated with lower A1c level . The treatment group significantly improved on the SDSCA subscales carbohydrate spacing ( P=.04 ) , monitoring glucose ( P=.001 ) , and foot care ( P=.02 ) . Conclusions An eHealth model incorporating a complete feedback loop with telehealth remote monitoring and paired glucose testing with asynchronous data analysis significantly improved A1c levels compared to usual care . Trial Registration Clinical trials.gov NCT01715649 ; https://www . clinical trials.gov/ct2/show/NCT01715649 ( Archived by WebCite at http://www.webcitation.org/6ZinLl8D0 )", "OBJECTIVE To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS For this study , 104 patients with diabetes and HbA(1c ) ( A1C ) > or = 9.0 % who received their care at a Department of Veterans Affairs medical center were recruited . All participants completed a diabetes education class and were r and omized to continue with their usual care ( n = 52 ) or receive web-based care management ( n = 52 ) . The web-based group received a notebook computer , glucose and blood pressure monitoring devices , and access to a care management website . The website provided educational modules , accepted uploads from monitoring devices , and had an internal messaging system for patients to communicate with the care manager . RESULTS Participants receiving web-based care management had lower A1C over 12 months ( P care . Persistent website users had greater improvement in A1C when compared with intermittent users ( -1.9 vs. -1.2 % ; P = 0.051 ) or education and usual care ( -1.4 % ; P website data uploads was associated with a larger decline in A1C ( highest tertile -2.1 % , lowest tertile -1.0 % ; P Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure ( P HDL cholesterol rose and triglycerides fell in the web-based group ( P Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes", "BACKGROUND Cardiovascular disease ( CVD ) and diabetes account for one-third of the mortality difference between African American and white patients . We evaluated the effect of a CVD risk reduction intervention in African Americans with diabetes . METHODS We r and omized 359 African Americans with type 2 diabetes to receive usual care or a nurse telephone intervention . The 12-month intervention provided monthly self-management support and quarterly medication management facilitation . Co primary outcomes were changes in systolic blood pressure ( SBP ) , hemoglobin A1c ( HbA1c ) , and low-density lipoprotein cholesterol ( LDL-C ) over 12 months . We estimated between-intervention group differences over time using linear mixed-effects models . The secondary outcome was self-reported medication adherence . RESULTS The sample was 72 % female ; 49 % had low health literacy , and 37 % had annual income Model-based estimates for mean baseline SBP , HbA1c , and LDL-C were 136.8 mm Hg ( 95 % CI 135.0 - 138.6 ) , 8.0 % ( 95 % CI 7.8 - 8.2 ) , and 99.1 mg/dL ( 95 % CI 94.7 - 103.5 ) , respectively . Intervention patients received 9.9 ( SD 3.0 ) intervention calls on average . Primary providers replied to 76 % of nurse medication management facilitation contacts , 18 % of these result ed in medication changes . There were no between-group differences over time for SBP ( P = .11 ) , HbA1c ( P = .66 ) , or LDL-C ( P = .79 ) . Intervention patients were more likely than those receiving usual care to report improved medication adherence ( odds ratio 4.4 , 95 % CI 1.8 - 10.6 , P = .0008 ) , but adherent patients did not exhibit relative improvement in primary outcomes . CONCLUSIONS This intervention improved self-reported medication adherence but not CVD risk factor control among African Americans with diabetes . Further research is needed to determine how to maximally impact CVD risk factors in African American patients", "OBJECTIVE —The purpose of this study was to determine whether implementation of a multicomponent organizational intervention can produce significant change in diabetes care and outcomes in community primary care practice s. RESEARCH DESIGN AND METHODS —This was a group-r and omized , controlled clinical trial evaluating the practical effectiveness of a multicomponent intervention ( TRANSLATE ) in 24 practice s. The intervention included implementation of an electronic diabetes registry , visit reminders , and patient-specific physician alerts . A site coordinator facilitated previsit planning and a monthly review of performance with a local physician champion . The principle outcomes were the percentage of patients achieving target values for the composite of systolic blood pressure ( SBP ) mmHg , LDL cholesterol A1C months , 69,965 visits from 8,405 adult patients with type 2 diabetes were recorded from 238 health care providers in 24 practice s from 17 health systems . Diabetes process measures increased significantly more in intervention than in control practice s , giving net increases as follows : foot examinations 35.0 % ( P annual eye examinations 25.9 % ( P renal testing 28.5 % ( P A1C testing 8.1%(P blood pressure monitoring 3.5 % ( P = 0.05 ) ; and LDL testing 8.6 % ( P Mean A1C adjusted for age , sex , and comorbidity decreased significantly in intervention practice s ( P recommended clinical values for SBP , A1C , and LDL than control clinics ( P = 0.002 ) . CONCLUSIONS — Introduction of a multicomponent organizational intervention in the primary care setting significantly increases the percentage of type 2 diabetic patients achieving recommended clinical outcomes ", "OBJECTIVE Web-based diabetes management can be used to provide frequent interactions between patients and providers and thus result in improved glycemic control . METHODS In a single-center , prospect i ve feasibility study , 16 poorly controlled patients with either type 1 or 2 diabetes mellitus were enrolled to assess the impact of using MyCareTeam , a web-based diabetes management application , for diabetes management . Patients were asked to transfer their blood glucose data electronically , maintain exercise logs , and communicate with their provider via MyCareTeam . The provider gave clinical interventions to optimize blood glucose control and provided feedback via MyCareTeam . Diabetes , nutrition , and exercise information was also available via MyCareTeam . RESULTS A significant reduction of over 2.22 % points in hemoglobin A1C was seen for the total patient population . Differences between moderate/heavy users ( n = 8) versus light/never users ( n = 8) of MyCareTeam were evaluated for intergroup differences based upon utilization . Moderate/heavy users had a significant 6-month A1C reduction of 3.15 percentage points compared with a reduction of 1.28 percentage points in light/never users . Other secondary end points were improved as well , including systolic blood pressure , diastolic blood pressure , total cholesterol , high-density lipoprotein , low-density lipoprotein , and triglycerides . However , as expected , body mass index levels increased because of aggressive diabetes management with insulin therapy . CONCLUSIONS These results demonstrate a significant treatment effect from the MyCareTeam application . A larger r and omized control trial is under way at the Boston Veterans Administration Healthcare System . If these results are confirmed as expected , then web-based diabetes management may prove to be the link to achieving target American Diabetes Association glycemic goals in patients with poorly controlled diabetes", "OBJECTIVE To improve quality and efficiency of care for elderly patients with type 2 diabetes , we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare ( u-healthcare ) service , which is an individualized health management system using advanced medical information technology . RESEARCH DESIGN AND METHODS We conducted a 6-month r and omized , controlled clinical trial involving 144 patients aged > 60 years . Participants were r and omly assigned to receive routine care ( control , n = 48 ) , to the self-monitored blood glucose ( SMBG , n = 47 ) group , or to the u-healthcare group ( n = 49 ) . The primary end point was the proportion of patients achieving A1C without hypoglycemia at 6 months . U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient ’s mobile phone . Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server . Once the data are transferred to the server , an automated system , the CDSS rule engine , generates and sends patient-specific messages by mobile phone . RESULTS After 6 months of follow-up , the mean A1C level was significantly decreased from 7.8 ± 1.3 % to 7.4 ± 1.0 % ( P proportion of patients with A1C was 30.6 % in the u-healthcare group , 23.4 % in the SMBG group ( 23.4 % ) , and 14.0 % in the control group ( P u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients", "BACKGROUND Behavioral research to improve lifestyle in broadly defined population s of patients with type 2 diabetes is limited . OBJECTIVE We evaluated a behavioral intervention featuring technology-based self-monitoring on biophysiologic outcomes of glycemic control and markers of cardiovascular risk . DESIGN In this single-site , r and omized clinical trial , participants were stratified by good and poor glycemic control ( glycated hemoglobin and r and omized within strata . Measurements were obtained at 0 , 3 , and 6 months . PARTICIPANTS / SETTING Self-referred , community-dwelling adults with type 2 diabetes mellitus . INTERVENTION The intervention group received Social Cognitive Theory-based counseling paired with technology-based self-monitoring , and results were compared with an attention control group . MAIN OUTCOME MEASURES Glycated hemoglobin , fasting serum glucose , lipid levels , blood pressure , weight , body mass index , and waist circumference were evaluated . STATISTICAL ANALYSES PERFORMED Mean differences within and between r and omization groups were compared over time . Intervention effects over time were estimated using r and om intercept models . RESULTS Two hundred ninety-six subjects were r and omized , 256 ( 86.5 % ) completed 3-month and 246 ( 83.1 % ) completed 6-month assessment s. Glycated hemoglobin was reduced in the intervention group by 0.5 % at 3 months and 0.6 % at 6 months ( P baseline glycated hemoglobin ≥8 % and estimated glomerular filtration rate ≥60 mL/min , glycated hemoglobin was reduced in the intervention group by 1.5 % at 3 months and 1.8 % at 6 months ( P reduction in glycated hemoglobin of 0.29 % was not significant . CONCLUSIONS Two behavioral approaches to improving general lifestyle management in individuals with type 2 diabetes mellitus were effective in improving glycemic control , but no significant between-group differences were observed", "OBJECTIVE —To test Web-based care management of glycemic control using a shared electronic medical record with patients who have type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a trial of 83 adults with type 2 diabetes r and omized to receive usual care plus Web-based care management or usual care alone between August 2002 and May 2004 . All patients had GHb ≥7.0 % , had Web access from home , and could use a computer with English language –based programs . Intervention patients received 12 months of Web-based care management . The Web-based program included patient access to electronic medical records , secure e-mail with providers , feedback on blood glucose readings , an educational Web site , and an interactive online diary for entering information about exercise , diet , and medication . The primary outcome was change in GHb . RESULTS —GHb levels declined by 0.7 % ( 95 % CI 0.2−1.3 ) on average among intervention patients compared with usual-care patients . Systolic blood pressure , diastolic blood pressure , total cholesterol levels , and use of in-person health care services did not differ between the two groups . CONCLUSIONS —Care management delivered through secure patient Web communications improved glycemic control in type 2 diabetes", "BACKGROUND Optimal care for patients with diabetes is difficult to achieve in clinical practice . OBJECTIVE To evaluate the impact of a registry and decision support system on processes of care , and physiologic control . PARTICIPANTS R and omized trial with clustering at the practice level , involving 7,412 adults with diabetes in 64 primary care practice s in the Northeast . INTERVENTIONS Provider decision support ( reminders for overdue diabetes tests , alerts regarding abnormal results , and quarterly population reports with peer comparisons ) and patient decision support ( reminders and alerts ) . MEASUREMENTS AND MAIN RESULTS Process and physiologic outcomes were evaluated in all subjects . Functional status was evaluated in a r and om patient sample via question naire . We used multiple logistic regression to quantify the effect , adjusting for clustering and potential confounders . Intervention subjects were significantly more likely to receive guideline -appropriate testing for cholesterol ( OR = 1.39 ; [ 95%CI 1.07 , 1.80 ] P = 0.012 ) , creatinine ( OR = 1.40 ; [ 95%CI 1.06 , 1.84 ] P = 0.018 ) , and proteinuria ( OR = 1.74 ; [ 95%CI 1.13 , 1.69 ] P = 0.012 ) , but not A1C ( OR = 1.17 ; [ 95 % CI 0.80 , 1.72 ] P = 0.43 ) . Rates of control of A1C and LDL cholesterol were similar in the two groups . There were no differences in blood pressure , body mass index , or functional status . CONCLUSIONS A chronic disease registry and decision support system based on easily obtainable laboratory data was feasible and acceptable to patients and providers . This system improved the process of laboratory monitoring in primary care , but not physiologic control", "OBJECTIVE —The Diabetes Care Protocol combines task delegation ( a practice nurse ) , computerized decision support , and feedback every 3 months . We studied the effect of the Diabetes Care Protocol on A1C and cardiovascular risk factors in type 2 diabetic patients in primary care . RESEARCH DESIGN AND METHODS —In a cluster r and omized trial , mean changes in cardiovascular risk factors between the intervention and control groups after 1 year were calculated by generalized linear models . RESULTS —Throughout the Netherl and s , 26 intervention practice s included 1,699 patients and 29 control practice s 1,692 patients . The difference in A1C change was not significant , whereas total cholesterol , LDL cholesterol , and blood pressure improved significantly more in the intervention group . The 10-year coronary heart disease risk estimate of the UK Prospect i ve Diabetes Study improved 1.4 % more in the intervention group . CONCLUSIONS —Delegation of routine diabetes care to a practice nurse combined with computerized decision support and feedback did not improve A1C but reduced cardiovascular risk in type 2 diabetes patients", "OBJECTIVE There is a pressing need for brief practical interventions that address diabetes management . Using a r and omized design , we evaluated a medical office-based intervention focused on behavioral issues relevant to dietary self-management . RESEARCH DESIGN AND METHODS There were 206 adult diabetes patients r and omized to usual care or brief intervention , which consisted of touchscreen computer-assisted assessment to provide immediate feedback on key barriers to dietary self-management , and goal setting and problem-solving counseling for patients . Follow-up components to the single session intervention included phone calls and interactive video or videotape instruction as needed . RESULTS Multivariate analyses of covariance revealed that the brief intervention produced greater improvements than usual care on a number of measures of dietary behavior ( e.g. , fewer calories from saturated fat , fewer high-fat eating habits and behaviors ) at the 3-month follow-up . There were also significant differences favoring intervention on changes in serum cholesterol levels and patient satisfaction but not on glycosylated hemoglobin . The intervention effects were relatively robust across a variety of patient characteristics , the two participating physicians , and intervention staff members . CONCLUSIONS If the long-term results are equally positive and generalize to other setting , this intervention could provide a prototype for a feasible cost-effective way to integrate patient views and behavioral management into office-based care for diabetes", "Abstract Background Following the introduction of a computerised diabetes register in part of the northeast of Engl and , care initially improved but then plateaued . We therefore enhanced the existing diabetes register to address these problems . The aim of the trial was to evaluate the effectiveness and efficiency of an area wide ' extended , ' computerised diabetes register incorporating a full structured recall and management system , including individualised patient management prompts to primary care clinicians based on locally-adapted , evidence -based guidelines . Methods The study design was a pragmatic , cluster r and omised controlled trial , with the general practice as the unit of r and omisation . Set in 58 general practice s in three Primary Care Trusts in the northeast of Engl and , the study outcomes were the clinical process and outcome variables held on the diabetes register , patient-reported outcomes , and service and patient costs . The effect of the intervention was estimated using generalised linear models with an appropriate error structure . To allow for the clustering of patients within practice s , population averaged models were estimated using generalized estimating equations . Results Patients in intervention practice s were more likely to have at least one diabetes appointment recorded ( OR 2.00 , 95 % CI 1.02 , 3.91 ) , to have a recording of a foot check ( OR 1.87 , 95 % CI 1.09 , 3.21 ) , have a recording of receiving dietary advice ( OR 2.77 , 95 % CI 1.22 , 6.29 ) , and have a recording of blood pressure ( BP ) ( OR 2.14 , 95 % CI 1.06 , 4.36 ) . There was no difference in mean HbA1c or BP levels , but the mean cholesterol level in patients from intervention practice s was significantly lower ( -0.15 mmol/l , 95 % CI -0.25 , -0.06 ) . There were no differences in patient-reported outcomes or in patient-reported use of drugs , or uptake of health services . The average cost per patient was not significantly different between the intervention and control groups . Costs incurred in administering the system at the register and in general practice were in addition to these . Conclusion This study has shown benefits from an area-wide , computerised diabetes register incorporating a full structured recall and individualised patient management system . However , these benefits were achieved at a cost . In future , these costs may fall as electronic data exchange becomes a reliable reality . Trial registration : International St and ard R and omised Controlled Trial Number ( IS RCT N ) Register , IS RCT N32042030", "OBJECTIVE Management of diabetes is frequently suboptimal in primary care setting s , where providers often fail to intensify therapy when glucose levels are high , a problem known as clinical inertia . We asked whether interventions targeting clinical inertia can improve outcomes . RESEARCH DESIGN AND METHODS A controlled trial over a 3-year period was conducted in a municipal hospital primary care clinic in a large academic medical center . We studied all patients ( 4,138 ) with type 2 diabetes who were seen in continuity clinics by 345 internal medicine residents and were r and omized to be control subjects or to receive one of three interventions . Instead of consultative advice , the interventions were hard copy computerized reminders that provided patient-specific recommendations for management at the time of each patient 's visit , individual face-to-face feedback on performance for 5 min every 2 weeks , or both . RESULTS Over an average patient follow-up of 15 months within the intervention site , improvements in and final HbA1c ( A1C ) with feedback + reminders ( deltaA1C 0.6 % , final A1C 7.46 % ) were significantly better than control ( deltaA1C 0.2 % , final A1C 7.84 % , P systolic blood pressure ( sBP ) and LDL cholesterol . Multivariable analysis showed that the feedback intervention independently facilitated attainment of American Diabetes Association goals for both A1C and sBP . Over a 2-year period , overall glycemic control improved in the intervention site but did not change in other primary care sites ( final A1C 7.5 vs. 8.2 % , P internal medicine resident primary care providers improves glycemic control . Partnering generalists with diabetes specialists may be important to enhance diabetes management in other primary care setting", "OBJECTIVE To test effects of a web-based decision support tool , the diabetes Disease Management Application ( DMA ) , developed to improve evidence -based management of type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a group r and omized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic . Providers were r and omly assigned from May 1998 through April 1999 to have access to the DMA ( intervention ) or not to have access ( control ) . The DMA displays interactive patient-specific clinical data , treatment advice , and links to other web-based care re sources . We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis . RESULTS The DMA was used for 42 % of scheduled patient visits . The number of HbA(1c ) tests obtained per year increased significantly in the intervention group ( + 0.3 tests/year ) compared with the control group ( -0.04 tests/year , P = 0.008 ) , as did the number of LDL cholesterol tests ( intervention , + 0.2 tests/year ; control , + 0.01 tests/year ; P = 0.02 ) and the proportions of patients undergoing at least one foot examination per year ( intervention , + 9.8 % ; control , -0.7 % ; P = 0.003 ) . Levels of HbA(1c ) decreased by 0.2 in the intervention group and increased by 0.1 in the control group ( P = 0.09 ) ; proportions of patients with LDL cholesterol levels < 130 mg/dl increased by 20.3 % in the intervention group and 10.5 % in the control group ( P = 0.5 ) . CONCLUSIONS Web-based patient-specific decision support has the potential to improve evidence -based parameters of diabetes care", "OBJECTIVE We evaluated automated telephone disease management ( ATDM ) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs ( VA ) clinics . We also compared the results with those of a prior ATDM trial conducted in a county health care system . RESEARCH DESIGN AND METHODS A total of 272 VA patients with diabetes using hypoglycemic medications were r and omized . During the 1-year study period , intervention patients received biweekly ATDM health assessment and self-care education calls , and a nurse educator followed up with patients based on their ATDM assessment reports . Telephone surveys were used to measure patients ' self-care , symptoms , and satisfaction with care . Outpatient service use was evaluated using electronic data bases and self-reports , and glycemic control was measured by HbA1c and serum glucose testing . RESULTS At 12 months , intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics . Intervention patients also were more likely than control patients to have had a cholesterol test . Among patients with baseline HbA1c levels > or = 8 % , mean end-point values were lower among intervention patients than control patients ( 8.7 vs. 9.2 % , respectively ; P = 0.04 ) . Among intervention and control patients with baseline values > or = 9 % , mean end-point values were 9.1 and 10.2 % , respectively ( P = 0.04 ) . At follow-up , intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care . CONCLUSIONS This intervention improved the quality of VA diabetes care . Intervention effects for most end points replicated findings from the prior county clinic trial , although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study 's enrollees", "CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care . OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older , ethnically diverse , medically underserved patients with diabetes . DESIGN , Setting , and Patients A r and omized controlled trial was conducted , comparing telemedicine case management to usual care , with blinded outcome evaluation , in 1,665 Medicare recipients with diabetes , aged > /= 55 years , residing in federally design ated medically underserved areas of New York State . Interventions Home telemedicine unit with nurse case management versus usual care . Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c ( HgbA1c ) , low density lipoprotein ( LDL ) cholesterol , and blood pressure levels . RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints ( HgbA1c , p = 0.001 ; LDL , p systolic and diastolic blood pressure , p = 0.024 ; p HgbA1c , 3.84 ( -0.08 , 7.77 ) mg/dL for LDL cholesterol , and 4.32 ( 1.93 , 6.72 ) mm Hg for systolic and 2.64 ( 1.53 , 3.74 ) mm Hg for diastolic blood pressure . There were 176 deaths in the intervention group and 169 in the usual care group ( hazard ratio 1.01 [ 0.82 , 1.24 ] ) . CONCLUSIONS Telemedicine case management result ed in net improvements in HgbA1c , LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries . Mortality was not different between the groups , although power was limited . Trial Registration http:// clinical trials.gov Identifier : NCT00271739", "OBJECTIVE The Mayo Health System Diabetes Translation Project sought to assess models of community-based diabetes care and use of a diabetes electronic management system ( DEMS ) . Planned care is a re design ed model of chronic disease care that involves guideline implementation , support of self-management , and use of clinical information systems . RESEARCH DESIGN AND METHODS We studied adult diabetic patients attending three primary care practice sites in Wisconsin and Minnesota . We implemented planned care at all sites and DEMS in the practice of 16 primary care providers . We assessed quality of diabetes care using st and ard indicators for 200 patients r and omly selected from each site at baseline and at 24 months of implementation . We used multivariable analyses to estimate the association between planned care and DEMS and each quality indicator . RESULTS Planned care was associated with improvements in measurement of HbA(1c ) ( odds ratio 7.0 [ 95 % CI 4.2 - 11.6 ] ) , HDL cholesterol ( 5.6 [ 4.1 - 7.5 ] ) , and microalbuminuria ( 5.3 [ 3.5 - 8.0 ] ) , as well as the provision of tobacco advice ( 6.9 [ 4.7 - 10.1 ] ) , among other performance measures . DEMS use was associated with improvements in all indicators , including microalbuminuria ( 3.2 [ 1.9 - 5.2 ] ) , retinal examination ( 2.4 [ 1.5 - 3.9 ] ) , foot examinations ( 2.3 [ 1.2 - 4.4 ] ) , and self-management support ( 2.6 [ 1.7 - 3.8 ] ) . Although planned care was associated with improvements in metabolic control , we observed no additional metabolic benefit when providers used DEMS . CONCLUSIONS Planned care was associated with improved performance and metabolic outcomes in primary care . DEMS use augmented the impact of planned care on performance outcomes but not on metabolic outcomes . Optimal identification of the best translation of evidence to diabetes practice will require longer follow-up or new care-delivery models", "BACKGROUND A prerequisite to translating research findings into practice is information on consistency of implementation , maintenance of results , and generalization of effects . This follow-up report is one of the few experimental studies to provide such information on Internet-based health education . METHODS We present follow-up data 10 months following r and omization on the \" Diabetes Network ( D-Net ) \" Internet-based self-management project , a r and omized trial evaluating the incremental effects of adding ( 1 ) tailored self-management training or ( 2 ) peer support components to a basic Internet-based , information-focused comparison intervention . Participants were 320 adult type 2 diabetes patients from participating primary care offices , mean age 59 ( SD = 9.2 ) , who were relatively novice Internet users . RESULTS All intervention components were consistently implemented by staff , but participant website usage decreased over time . All conditions were significantly improved from baseline on behavioral , psychosocial , and some biological outcomes ; and there were few differences between conditions . Results were robust across on-line coaches , patient characteristics , and participating clinics . CONCLUSIONS The basic D-Net intervention was implemented well and improvements were observed across a variety of patients , interventionists , and clinics . There were , however , difficulties in maintaining usage over time and additions of tailored self-management and peer support components generally did not significantly improve results", "OBJECTIVE To assess the effect of a specialist telemedicine intervention for improving diabetes care using the chronic care model ( CCM ) . PARTICIPANTS AND METHODS As part of the CCM , 97 primary care physicians at 6 primary care practice s in Rochester , MN , referred 639 patients to an on-site diabetes educator between July 1 , 2001 , and December 31 , 2003 . On first referral , physicians were central ly r and omized to receive a telemedicine intervention ( specialty advice and evidence -based messages regarding medication management for cardiovascular risk ) or no intervention , keeping outcome assessors and data analysts blinded to group assignment . After each subsequent clinical encounter , endocrinologists review ed an abstract from the patient 's electronic medical record and provided management recommendations and supporting evidence to intervention physicians via e-mail . Control physicians received e-mail with periodic generic information about cardiovascular risk reduction in diabetes . Outcome measures included diabetes care processes ( diabetes test completion ) , outcomes ( metabolic and cardiovascular risk factors , estimated coronary artery disease risk ) , and patient costs ( payer perspective ) . RESULTS During the intervention , 951 ( 70 % ) of the 1361 endocrinology review s detected performance gaps and result ed in a message ; primary care physicians reported using 49 % of messages in patient care . With a mean of 21 months ' follow-up , the intervention , compared with control , did not significantly enhance metabolic outcomes or reduce estimated risk of coronary artery disease ( adjusted mean difference , -1 % ; 95 % confidence interval , -19 % to 17 % ) . The intervention group incurred lower costs ( P=.02 ) but not in diabetes-related costs . CONCLUSION Specialty telemedicine did not significantly enhance the value of CCM in primary care", "BACKGROUND Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus ( IDDM ) . We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications . METHODS A total of 1441 patients with IDDM--726 with no retinopathy at base line ( the primary -prevention cohort ) and 715 with mild retinopathy ( the secondary -intervention cohort ) were r and omly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections . The patients were followed for a mean of 6.5 years , and the appearance and progression of retinopathy and other complications were assessed regularly . RESULTS In the primary -prevention cohort , intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent ( 95 percent confidence interval , 62 to 85 percent ) , as compared with conventional therapy . In the secondary -intervention cohort , intensive therapy slowed the progression of retinopathy by 54 percent ( 95 percent confidence interval , 39 to 66 percent ) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent ( 95 percent confidence interval , 14 to 67 percent ) . In the two cohorts combined , intensive therapy reduced the occurrence of microalbuminuria ( urinary albumin excretion of > or = 40 mg per 24 hours ) by 39 percent ( 95 percent confidence interval , 21 to 52 percent ) , that of albuminuria ( urinary albumin excretion of > or = 300 mg per 24 hours ) by 54 percent ( 95 percent confidence interval 19 to 74 percent ) , and that of clinical neuropathy by 60 percent ( 95 percent confidence interval , 38 to 74 percent ) . The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia . CONCLUSIONS Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy , nephropathy , and neuropathy in patients with IDDM", "Background : Diabetes mellitus is a complex disease with serious complications . Electronic decision support , providing information that is shared and discussed by both patient and physician , encourages timely interventions and may improve the management of this chronic disease . However , it has rarely been tested in community-based primary care . Methods : In this pragmatic r and omized trial , we r and omly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care . The intervention involved shared access by the primary care provider and the patient to a Web-based , colour-coded diabetes tracker , which provided sequential monitoring values for 13 diabetes risk factors , their respective targets and brief , prioritized messages of advice . The primary outcome measure was a process composite score . Secondary outcomes included clinical composite scores , quality of life , continuity of care and usability . The outcome assessors were blinded to each patient ’s intervention status . Results : We recruited sequentially 46 primary care providers and then 511 of their patients ( mean age 60.7 [ st and ard deviation 12.5 ] years ) . Mean follow-up was 5.9 months . The process composite score was significantly better for patients in the intervention group than for control patients ( difference 1.27 , 95 % confidence interval [ CI ] 0.79–1.75 , p clinical composite score also had significantly more variables with improvement for the intervention group ( 0.59 , 95 % CI 0.09–1.10 , p = 0.02 ) , including significantly greater declines in blood pressure ( −3.95 mm Hg systolic and −2.38 mm Hg diastolic ) and glycated hemoglobin ( −0.2 % ) . Patients in the intervention group reported greater satisfaction with their diabetes care . Interpretation : A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care . ( Clinical Trials.gov trial register no. NCT00813085 .", "BACKGROUND The emergence of the World Wide Web in the last decade has made it feasible for the Internet to be a vehicle for chronic disease management . METHODS A r and omized controlled trial ( n = 62 ) testing the effects of a 6-month web-based intervention plus usual care , compared with usual care alone , among adults 60 years of age and older with diabetes . The outcomes were hemoglobin A1c ( HbA1c ) , blood pressure , weight , cholesterol , and high-density lipoprotein ( HDL ) levels . RESULTS A multivariate analysis of covariance controlling for all baseline outcome variables , age , gender , and number of years with diabetes showed significant ( P = 0.001 ) reductions in HbA1c , weight , and cholesterol level and significant improvement in HDL levels in the intervention versus the control group . CONCLUSIONS Findings show a web-based intervention was effective in improving HbA1c , weight , cholesterol , and HDL levels at a 6-month follow-up . Future research is needed to investigate the long-term effectiveness of web-based interventions", "BACKGROUND Disease registries , audit and feedback , and clinical reminders have been reported to improve care processes . OBJECTIVE To assess the effects of a registry-generated audit , feedback , and patient reminder intervention on diabetes care . DESIGN R and omized controlled trial conducted in a resident continuity clinic during the 2003–2004 academic year . PARTICIPANTS Seventy-eight categorical Internal Medicine residents caring for 483 diabetic patients participated . Residents r and omized to the intervention ( n = 39 ) received instruction on diabetes registry use ; quarterly performance audit , feedback , and written reports identifying patients needing care ; and had letters sent quarterly to patients needing hemoglobin A1c or cholesterol testing . Residents r and omized to the control group ( n = 39 ) received usual clinic education . MEASUREMENTS Hemoglobin A1c and lipid monitoring , and the achievement of intermediate clinical outcomes ( hemoglobin A1c were assessed . RESULTS Patients cared for by residents in the intervention group had higher adherence to guideline recommendations for hemoglobin A1c testing ( 61.5 % vs 48.1 % , p = .01 ) and LDL testing ( 75.8 % vs 64.1 % , p = .02 ) . Intermediate clinical outcomes were not different between groups . CONCLUSIONS Use of a registry-generated audit , feedback , and patient reminder intervention in a resident continuity clinic modestly improved diabetes care processes , but did not influence intermediate clinical outcomes", "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 Web-based personal health records ( PHRs ) have been advocated as a means to improve type 2 diabetes mellitus ( DM ) care . However , few Web-based systems are linked directly to the electronic medical record ( EMR ) used by physicians . METHODS We r and omized 11 primary care practice s. Intervention practice s received access to a DM-specific PHR that imported clinical and medications data , provided patient-tailored decision support , and enabled the patient to author a \" Diabetes Care Plan \" for electronic su bmi ssion to their physician prior to upcoming appointments . Active control practice s received a PHR to up date and su bmi t family history and health maintenance information . All patients attending these practice s were encouraged to sign up for online access . RESULTS We enrolled 244 patients with DM ( 37 % of the eligible population with registered online access , 4 % of the overall population of patients with DM ) . Study participants were younger ( mean age , 56.1 years vs 60.3 years ; P ( median income , $ 53,784 vs $ 49,713 ; P baseline glycemic control compared with non participants . More patients in the intervention arm had their DM treatment regimens adjusted ( 53 % vs 15 % ; P DM-related medication adjustment . Low rates of online patient account registration and good baseline control among participants limited the intervention 's impact on overall risk factor control . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00251875", "OBJECTIVE The public is increasingly aware of the importance of HbA(1c ) testing , yet the vast majority of patients with diabetes do not know their HbA(1c ) status or goal . We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS A total of 150 patients with diabetes were r and omized to receive either st and ard care or intervention inclusive of a computer-generated 11 \" x 17 \" color poster depicting an individual 's HbA(1c ) status and goals along with personalized steps to aid in goal achievement . All patients enrolled received diabetes education during the 3 months before enrollment . HbA(1c ) was performed at baseline and 6 months . RESULTS At baseline , there were no significant differences between patient groups in terms of age , sex , education level , race , and HbA(1c ) or lipid levels . Among patients with baseline HbA(1c ) > or = 7.0 % , there was an 8.6 % ( 0.77 % absolute ) reduction in HbA(1c ) among control subjects compared with a 17.0 % ( 1.69 % absolute ) decline in the intervention group ( P = 0.032 ) . There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA(1c ) ( 63 vs. 69 % , P = 0.87 ) ; among these patients experiencing a decline , the most substantial reductions were seen with the control group , which had a 13.3 % ( 1.15 % absolute ) decline compared with the intervention patients , who reduced their HbA(1c ) by 24.2 % ( 2.26 % absolute reduction ; P = 0.0048 ) . At study close , 77 % of the patients had their poster displayed on their refrigerator . CONCLUSIONS This unique and personalized computer-generated intervention result ed in HbA(1c ) lowering comparable to that of hypoglycemic agents", "PURPOSE We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes . SUBJECTS AND METHODS We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system . Patients were r and omly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator . Outcomes measured at 12 months included survey-reported self-care , perceived glycemic control , and symptoms , as well as glycosylated hemoglobin ( Hb A1c ) and serum glucose levels . RESULTS We collected follow-up data for 89 % of enrollees ( 248 patients ) . Compared with usual care patients , intervention patients reported more frequent glucose monitoring , foot inspection , and weight monitoring , and fewer problems with medication adherence ( all P -0.03 ) . Follow-up Hb A , , levels were 0.3 % lower in the intervention group ( P = 0.1 ) , and about twice as many intervention patients had Hb A1c levels within the normal range ( P = 0.04 ) . Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients ( P = 0.002 ) . Intervention patients also reported better glycemic control ( P = 0.005 ) and fewer diabetic symptoms ( P symptoms of hyperglycemia and hypoglycemia . CONCLUSIONS Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control , and for decreasing symptoms among vulnerable patients with diabetes", "RATIONALE , AIMS AND OBJECTIVES Utilizing information technology , such as Internet and cellphones , holds great promise in enhancing diabetic care . Yet few studies have examined the impact of cellphone technology on type 2 diabetics ' self-care . The primary aim of the study is to examine the feasibility of utilizing this technology to assist with diabetes self-care in a clinic population as well as its impact on clinical outcomes . METHODS Thirty patients with a diagnosis of type 2 diabetes at two Community Health Centers were r and omized to intervention or control . Intervention patients participated in a brief intervention and received tailored daily messages via cellphone prompting them to enhance their diabetic self-care behaviour . Patients at the control site continued with their st and ard diabetes self-management . RESULTS A mean improvement in HbA1c levels was apparent ( -0.1 , SD = 0.3 % ; P = 0.1534 ) in the intervention group , compared with a mean deterioration in the control ( 0.3 , SD = 1.0 % ; P = 0.3813 ) , yet without statistical significance . Self-efficacy scores improved significantly in the intervention group ( -0.5 , SD = 0.6 ; P = 0.0080 ) compared with no improvement in the control ( 0.0 , SD = 1.0 ; P = 0.9060 ) . Participants encountered numerous technological barriers when attempting to adhere to the intervention protocol . CONCLUSION The results indicate the intervention had a positive impact on some clinical outcome and self-efficacy . Although the technology appears feasible in a clinical setting technology must be made more user-friendly before a larger phase II trial is conducted", "Effective control of diabetes is known to delay or prevent the end-organ complications of this disease . Can telemedicine improve a patient 's ability to self-manage diabetes ? Twenty-eight patients entered a study comparing home telemedicine consultation with st and ard outpatient care . A nurse case manager contacted the telemedicine group once a week under the direction of a primary care physician , who contacted the telemedicine group once a month . Laboratory studies and total body weight were measured at the beginning and at the end of the 3-month study . The hemoglobin A1c ( HbA1c ) and total body weight improved significantly in the intervention ( telemedicine ) group , as shown by a 16 % reduction in mean HbA1c level ( from 9.5 to 8.2 % ) and a 4 % mean weight reduction ( from 214.3 to 206.7 pounds ) . Based on our experience , we present a functionally based telemedicine classification system to improve the application of electronic medicine in future studies", "OBJECTIVE To examine across seven countries the relationship between physician office information system capacity and the quality of care . DESIGN Multivariate analysis of a cross-sectional 2006 r and om survey of primary care physicians in seven countries : Australia , Canada , Germany , the Netherl and s , New Zeal and , United Kingdom , and United States . MAIN OUTCOME MEASURES coordination and safety of care , care for chronically ill patients , and satisfaction with practice of medicine . RESULTS The study finds significant disparities in the quality of health care between practice s with low information system capacity and those with high technical capacity after controlling for within country differences and practice size . There were significant physician satisfaction differences with the overall experience of practicing medicine by information system level . CONCLUSIONS For policy leaders , the seven-nation survey suggests that health systems that promote information system infrastructure are better able to address coordination and safety issues , particularly for patients with multiple chronic conditions , as well as to maintain primary care physician workforce satisfaction", "PURPOSE We wanted to assess the impact of an electronic health record – based diabetes clinical decision support system on control of hemoglobin A1c ( glycated hemoglobin ) , blood pressure , and low-density lipoprotein ( LDL ) cholesterol levels in adults with diabetes . METHODS We conducted a clinic-r and omized trial conducted from October 2006 to May 2007 in Minnesota . Included were 11 clinics with 41 consenting primary care physicians and the physicians ’ 2,556 patients with diabetes . Patients were r and omized either to receive or not to receive an electronic health record (EHR)–based clinical decision support system design ed to improve care for those patients whose hemoglobin A1c , blood pressure , or LDL cholesterol levels were higher than goal at any office visit . Analysis used general and generalized linear mixed models with repeated time measurements to accommo date the nested data structure . RESULTS The intervention group physicians used the EHR-based decision support system at 62.6 % of all office visits made by adults with diabetes . The intervention group diabetes patients had significantly better hemoglobin A1c ( intervention effect −0.26 % ; 95 % confidence interval , −0.06 % to −0.47 % ; P=.01 ) , and better maintenance of systolic blood pressure control ( 80.2 % vs 75.1 % , P=.03 ) and borderline better maintenance of diastolic blood pressure control ( 85.6 % vs 81.7 % , P = .07 ) , but not improved low-density lipoprotein cholesterol levels ( P = .62 ) than patients of physicians r and omized to the control arm of the study . Among intervention group physicians , 94 % were satisfied or very satisfied with the intervention , and moderate use of the support system persisted for more than 1 year after feedback and incentives to encourage its use were discontinued . CONCLUSIONS EHR-based diabetes clinical decision support significantly improved glucose control and some aspects of blood pressure control in adults with type 2 diabetes" ]

[ "BACKGROUND The st and ard treatment for cobalamin ( vitamin B(12 ) ) deficiency involves regular intramuscular cobalamin injection . It has been suggested that oral cobalamin therapy may be effective for treating patients who have food-cobalamin malabsorption . SUBJECTS AND METHODS We prospect ively studied 10 patients with cobalamin deficiency and well-established food-cobalamin malabsorption who received 3000 microg or 5000 microg of oral crystalline cyanocobalamin once a week for at least 3 months . Complete blood counts and serum cobalamin , homocysteine , and folate levels were determined at baseline and after 3 months of treatment . Patients were reexamined after 6 months . RESULTS After 3 months of treatment , all patients had increased hemoglobin levels ( mean increase , 1.9 g/dL ; 95 % confidence interval : 0.9 to 3.9 g/dL;P decreased erythrocyte cell volume ( mean decrease , 7.8 fL ; 95 % confidence interval : 0.9 to 16.5 fL;P Serum cobalamin levels were increased in all 8 patients in whom it was measured . CONCLUSION Our findings suggest that moderate doses of crystalline cyanocobalamin given orally may be an effective treatment for food-cobalamin malabsorption", "AIMS To investigate the nasal absorption of hydroxocobalamin in 10 healthy elderly adults . METHODS In a cross-over study , blood sample s were collected before administration of the drug and after 10 , 20 , 30 , 40 , 60 , 120 , 180 and 240 min . The plasma cobalamin concentration was determined by competitive radioisotope binding technique . RESULTS The maximal plasma cobalamin concentration ( Cmax ) after nasal administration of 750 microg hydroxocobalamin was 1900 + /- 900 pmol l(-1 ) ( mean + /- s.d . ) . The maximal plasma cobalamin concentration was reached in 35 + /- 13 min ( t[max ] ) . The Cmax after nasal administration of 1500 microg hydroxocobalamin was 3500 + /- 2500 pmol l(-1 ) with a t(max ) of 28 + /- 16 min . Both the AUC(0,240 min ) and AUC(0,00 ) increased significantly with an increase of the dose from 750 microg to 1500 microg ( P = 0.037 and P = 0.028 , respectively ) . The nasal spray was well tolerated . No signs of irritation or local sensitivity were noted . CONCLUSIONS The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid , high and well tolerated", "Because cobalamin deficiency is routinely treated with parenteral cobalamin , we investigated the efficacy of oral therapy . We r and omly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1 , 3 , 7 , 10 , 14 , 21 , 30 , 60 , and 90 or 2 mg orally on a daily basis for 120 days . Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin ( normal , 200 to 900 pg/mL ) methylmalonic acid ( normal , 73 to 271 nmol/L ) , and homocysteine ( normal , 5.1 to 13.9 micromol/L ) . Five patients were subsequently found to have folate deficiency , which left 18 evaluable patients in the oral group and 15 in the parenteral group . Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups . The mean pretreatment values for serum cobalamin , methylmalonic acid , and homocysteine were , respectively , 93 pg/mL , 3,850 nmol/L , and 37 . 2 micromol/L in the oral group and 95 pg/mL , 3,630 nmol/L , and 40.0 micromol/L in the parenteral therapy group . After 4 months of therapy , the respective mean values were 1,005 pg/mL , 169 nmol/L , and 10.6 micromol/L in the oral group and 325 pg/mL , 265 nmol/L , and 12.2 micromol/L in the parenteral group . The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant , with P cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior", "BACKGROUND Cobalamin ( vitamin B12 ) deficiency , the most common cause of megaloblastic anemia , is treated with intramuscular ( IM ) cobalamin . It has been suggested by some investigators that oral ( p.o . ) cobalamin treatment may be as effective in the treatment of this condition , with the advantages of ease of administration and lower cost . OBJECTIVE This study assessed the effects and cost of p.o . versus i.m . cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency . METHODS This was a 90-day , prospect i ve , r and omized , open-label study conducted at the Division of Hematology , Department of Internal Medicine , Adnan Menderes University Research and Practice Hospital ( Aydin , Turkey ) . Patients aged > or = 16 years with megaloblastic anemia due to cobalamin deficiency were r and omized to receive 1000-microg cobalamin p.o . once daily for 10 days ( p.o . group ) or 1000-microg cobalamin i.m . once daily for 10 days ( i.m . group ) . After 10 days , both treatments were administered once a week for 4 weeks , and after that , once a month for life . Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected . Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0 , 10 , 30 , and 90 and serum vitamin B12 concentration on days 0 and 90 . The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing . Neurologic sensory assessment , including soft-touch and pinprick examinations , was used to identify neuropathy at baseline and study end . Tolerability was assessed using laboratory tests and patient interview . Cost was assessed using the cost of the study drug and of the injection . RESULTS Sixty patients completed the study 26 in the p.o . group ( 16 men , 10 women ; mean [ SD ] age , 60 [ 15 ] years ) and 34 in the i.m . group ( 17 men , 17 women ; mean [ SD ] age , 64 [ 10 ] years ) . Reticulocytosis was observed in all patients . In the p.o . group , at days 30 and 90 , all hematologic parameters changed significantly versus day 0 ( mean hemoglobin levels increased [ both P mean corpuscular volume decreased [ both P blood cell count increased [ day 30 , P mean platelet count increased [ both P The mean serum vitamin B12 concentration increased significantly from day 0 to 90 ( P hematologic parameters and the recovery patterns were similar between the 2 groups . Neurologic findings included sensitive peripheral neuropathy in 9 patients ( 15.0 % ) , alteration of cognitive function ( loss of memory , impaired concentration ) in 7 patients ( 11.7 % ) , and loss of sense of vibration in 5 patients ( 8.3 % ) . Neurologic improvement was detected in 7 of 9 patients ( 77.8 % ) in the p.o . group and 9 of 12 patients ( 75.0 % ) in the i.m . group at day 30 . CONCLUSIONS In this study of patients with megaloblastic anemia due to cobalamin deficiency , p.o . cobalamin treatment was as effective as i.m . cobalamin treatment . P.o . treatment also was better tolerated and less expensive compared with IM treatment . However , because of the small sample size and the short term of this study , further long-term studies are needed to determine the efficacy of p.o . cobalamin treatment", "A cross-sectional survey was conducted in order to describe the use of oral cobalamin among geriatricians , hematologists , and general practitioners , and to explore factors related to its use . The study population consisted of all geriatricians ( n = 138 ) and hematologists ( n = 317 ) listed in the Canadian Medical Directory plus a r and om sample of 307 general practitioners . The overall response rate was 40 % . Intramuscular and oral cobalamin was prescribed by 76 and 32 % of the respondents , respectively . Twenty seven percent reported using both oral and intramuscular cobalamin and 6 % reported using only oral cobalamin . Only 25 % of respondents indicated they were aware of a RCT demonstrating the efficacy of oral cobalamin prior to reading a synopsis of the study in the survey . After multivariate adjustment , only the belief that oral cobalamin was effective and certainty about who carried oral preparations remained independently associated with oral cobalamin use . Oral cobalamin has been shown to be an efficacious , cost efficient and safe method of treating cobalamin deficiency . Nonetheless , it is not used by the majority of physicians treating this condition . Strategies to promote the use of oral cobalamin should be directed at educating physicians of its efficacy and providing them with prescribing information on where it can be purchased", "BACKGROUND Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B(12 ) deficiency , but the effects of lower oral doses of cobalamin on such markers are uncertain . METHODS We conducted a r and omized , parallel-group , double-blind , dose-finding trial to determine the lowest oral dose of cyanocobalamin required to normalize biochemical markers of vitamin B(12 ) deficiency in older people with mild vitamin B(12 ) deficiency , defined as a serum vitamin B(12 ) level of 100 to 300 pmol/L ( 135 - 406 pg/mL ) and a methylmalonic acid level of 0.26 mumol/L or greater . We assessed the effects of daily oral doses of 2.5 , 100 , 250 , 500 , and 1000 mug of cyanocobalamin administered for 16 weeks on biochemical markers of vitamin B(12 ) deficiency in 120 people . The main outcome measure was the dose of oral cyanocobalamin that produced 80 % to 90 % of the estimated maximal reduction in the plasma methylmalonic acid concentration . RESULTS Supplementation with cyanocobalamin in daily oral doses of 2.5 , 100 , 250 , 500 , and 1000 mug was associated with mean reductions in plasma methylmalonic acid concentrations of 16 % , 16 % , 23 % , 33 % , and 33 % , respectively . Daily doses of 647 to 1032 mug of cyanocobalamin were associated with 80 % to 90 % of the estimated maximum reduction in the plasma methylmalonic acid concentration . CONCLUSION The lowest dose of oral cyanocobalamin required to normalize mild vitamin B(12 ) deficiency is more than 200 times greater than the recommended dietary allowance , which is approximately 3 mug daily", "BACKGROUND It has been suggested that oral cobalamin ( vitamin ( B12 ) ) therapy may be an effective therapy for treating cobalamin deficiencies related to food-cobalamin malabsorption . However , the duration of this treatment was not determined . PATIENTS AND METHOD In an open-label , nonplacebo study , we studied 30 patients with established cobalamin deficiency related to food-cobalamin malabsorption , who received between 250 and 1000 microg of oral crystalline cyanocobalamin per day for at least 1 month . ENDPOINTS Blood counts , serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment . RESULTS During the first month of treatment , 87 % of the patients normalized their serum cobalamin levels ; 100 % increased their serum cobalamin levels ( mean increase , + 167 pg/dl ; P medullary regeneration ; 100 % corrected their initial macrocytosis ; and 54 % corrected their anemia . All patients had increased hemoglobin levels ( mean increase , + 0.6 g/dl ) and reticulocyte counts ( mean increase , + 35 x 10(6)/l ) and decreased erythrocyte cell volume ( mean decrease , 3 fl ; all P cyanocobalamin , 250 - 1000 microg/day , given orally for 1 month , may be an effective treatment for cobalamin deficiencies not related to pernicious anemia", "BACKGROUND & AIMS Patients with previous stomach and terminal ileum resections are often treated with intramuscular vitamin B12 injections . Disadvantages are , on a worldwide scale , the frequent need for medical personnel to administer injections and the sometimes painful way of application . This study was design ed to investigate the feasibility of intranasal hydroxocobalamin suppletion in cobalamin-deficient patients and to assess whether intranasal hydroxocobalamin application could be an alternative for intramuscular injection . METHODS Six patients with plasma cobalamin concentrations of A dose of 1500 micrograms hydroxocobalamin was applied intranasally at days 0 , 14 , and 21 . Plasma cobalamin concentrations were determined 1 hour after hydroxocobalamin application and on days 0 , 7 , 21 , 28 , and 35 . RESULTS All patients showed substantial increase of cobalamin concentrations 1 hour after intranasal application . In these 6 patients , there was an eightfold increase of mean baseline cobalamin concentrations . All patients showed a sustained increase of baseline cobalamin concentrations 1 week after prior intranasal application of hydroxocobalamin . No side effects were noted . CONCLUSIONS Intranasal application of hydroxocobalamin in cobalamin-deficient patients results in fast nasal absorption and leads to sustained increase of baseline cobalamin concentrations", "OBJECTIVES The aim of this trial was to demonstrate the efficacy of one month of oral cobalamin ( vitamin B12 ) therapy in elderly patients with cobalamin deficiency related to food-cobalamin malabsorption ( FCM ) . PATIENTS AND METHOD Twenty elderly patients ( mean age : 78+/-17 years ) with established cobalamin deficiency related to FCM were included in an open-label , non-r and omized , non-placebo trial . They were treated with a maximum of 1,000 microgram per day of oral crystalline cyanocobalamin for at least 1 month . Serum cobalamin levels ( primary endpoint ) , blood count abnormalities and reticulocytes count ( secondary endpoints ) were determined at baseline and during the first month of treatment . RESULTS 85 % of the patients normalized their serum cobalamin levels with a mean increase of+167 pg/ml ( p macrocytosis and 25 % their anemia ; 100 % of the patients had medullar regeneration with a mean increase of reticulocytes count of 32+/-11.3 x 106/l ( p=0.03 compared with baseline ) . CONCLUSIONS Our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM" ]

[ "PURPOSE AND METHODS Although a high prevalence of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy ( CT ) has been reported , little has been done to develop strategies to prevent these problems . A double-blind , placebo-controlled study was therefore design ed to assess the usefulness of adding low-dose alprazolam ( 0.5 mg to 2 mg per day ) to a psychologic support program including progressive relaxation training design ed to prevent the aforementioned conditions . Fifty-seven women undergoing adjuvant CT for stage II primary breast cancer agreed to participate in the assessment , which was conducted at four time points : before starting CT , 6 weeks after CT , before the fourth CT , and after the fourth CT . The Hospital Anxiety and Depression Scale ( HADS ) , Montgomery and Asberg Depression Rating Scale ( MADRS ) , Hamilton Anxiety Scale ( HAS ) , Revised Symptom Checklist ( SCL-90-R ) , Morrow Assessment of Nausea and Emesis ( MANE ) , and World Health Organization ( WHO ) grading of acute and subacute toxicities were used to compare the alprazolam ( AA ) and placebo ( PA ) arms of the study . RESULTS At the second evaluation , the results showed a higher rate of anticipatory nausea ( 18 % v 0 % ) in the PA compared with the AA arm ( P = .038 ) . These differences were no more significant at each of the further assessment s. Significant differences were found for the intake of hypnotics at each assessment visit , with the rate of hypnotic users being significantly higher in the PA ( 19 % ) compared with the AA ( 0 % ) arm at the fourth assessment ( P Anxiety and depression scores of self- and observer-report were similar in the two arms . A significant relationship was found between the development of anticipatory nausea and the self-report of anxiety and depression score measured by HADS at baseline . The average HADS total score at baseline was 15.33 ( SD = 6.56 ) for patients who developed anticipatory nausea and 11.23 ( SD = 6.67 ) for other patients . CONCLUSION The adjunct of alprazolam to a psychologic support program delays the occurrence of anticipatory nausea and controls sleeping problems secondary to adjunct CT . Although studies are needed to improve the efficacy reported here , physicians may already consider the use of alprazolam for cancer patients undergoing CT", "Objective To examine the effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin . Aprepitant is a neurokinin-1 (NK1)-receptor antagonist developed as an antiemetic for chemotherapy-induced nausea and vomiting . Methods This was a double-blind , placebo-controlled , r and omized , two-period , parallel-group study . During period 1 , warfarin was individually titrated to a stable prothrombin time ( expressed as international normalized ratio , INR ) from 1.3 to 1.8 . Subsequently , the daily warfarin dose remained fixed for 10–12 days . During period 2 , the warfarin dose was continued for 8 days , and on days 1–3 administered concomitantly with aprepitant ( 125 mg on day 1 , and 80 mg on days 2 and 3 ) or placebo . At baseline ( day −1 of period 2 ) and on day 3 , warfarin pharmacokinetics was investigated . INR was monitored daily . During period 2 , warfarin trough concentrations were determined daily . Results The study was completed by 22 healthy volunteers ( 20 men , 2 women ) . On day 3 , steady-state pharmacokinetics of warfarin enantiomers after aprepitant did not change , as assessed by warfarin AUC0 - 24h and Cmax . However , compared with placebo , trough S(− ) warfarin concentrations decreased on days 5–8 ( maximum decrease 34 % on day 8 , P decreased after aprepitant with a mean maximum decrease on day 8 of 11 % versus placebo ( P=0.011 ) . Conclusion These data are consistent with a significant induction of CYP2C9 metabolism of S(− ) warfarin by aprepitant . Subsequently , in patients on chronic warfarin therapy , the clotting status should be monitored closely during the 2-week period , particularly at 7–10 days , following initiation of the 3-day regimen of aprepitant with each chemotherapy cycle", "Summary Purpose : To evaluate the efficacy and safety of amrubicin , (+)-(7S , 9S)-9-acetyl-9-amino-7-[(2-deoxy-β-D-erythro-pentopyranosyl ) oxy ] -7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-naphthacenedione hydrochloride , in previously untreated patients with extensive-disease small cell lung cancer ( SCLC ) . Patients and methods : A total of 35 previously untreated patients with extensive-disease SCLC were entered into the study . Amrubicin was given by daily intravenous infusion at 45 mg/m2/day for 3 consecutive days , every 3 weeks . Unless there was tumor regression of 25 % or greater after the first cycle , or 50 % or greater after the second cycle , treatment was switched to salvage chemotherapy in combination with etoposide ( 100 mg/m2 , days 1 , 2 , and 3 ) and cisplatin ( 80 mg/m2 , day 1 ) . Results : Of the 35 patients entered , 33 were eligible and assessable for efficacy and toxicity . Of the 33 patients , 3 ( 9.1 % ) had a complete response ( 95 % confidence interval [ CI ] , 1.9–24.3 % ) and 22 had a partial response , for an overall response rate of 75.8 % ( 95 % CI , 57.7–88.9 % ) . Median survival time was 11.7 months ( 95 % CI , 9.9–15.3 months ) , and 1-year and 2-year survival rates were 48.5 % and 20.2 % , respectively . The most common toxicity was hematologic . Non-hematologic toxicity of grade 3 or 4 was only seen in 3 patients with anorexia ( 9.1 % ) and 1 patient with alopecia ( 3.0 % ) . Salvage chemotherapy was administered to only 6 patients . Conclusion : Amrubicin was active for extensive-disease SCLC with acceptable toxicity . Further studies in combination with other agents for SCLC are warranted", "The efficacy and safety of granisetron and ondansetron for the prophylaxis of nausea and vomiting result ing from hyperfractionated total body irradiation ( TBI ) were assessed . Thirty-four patients r and omly received double-blind , oral granisetron ( 2 mg , 1 h before first daily fraction of radiation ) or ondansetron ( 8 mg , 1.5 h prior to each fraction of TBI ) . Ninety patients who received the same TBI regimen prior to bone marrow transplantation ( BMT ) , but no 5-HT3-receptor antagonist , were identified and comprised the historical control group . By design , this study was only powered to show a difference between each of the active treatment groups and the historical control group . Significantly more patients given granisetron ( 33.3 % ) or ondansetron ( 26.7 % ) had zero emetic episodes over 4 days , the primary efficacy end point , than those in the historical control group ( 0 % ) ( P Secondary efficacy end points were also evaluated . during the first 24 h , significantly more patients taking granisetron ( 61.1 % ) or ondansetron ( 46.7 % ) had zero emetic episodes than patients in the historical control group ( 6.7 % ) ( P Complete emetic control ( no emesis or rescue antiemetic ) over 4 days was more frequent in patients taking granisetron ( 27.8 % ) or ondansetron ( 26.7 % ) compared with the historical control group ( 0 % ) ( P granisetron ( 18/18 ) , but not those taking ondansetron ( 12/15 ) , experienced more than five emetic episodes during the 4 days of the study compared with the historical control group ( 40/90 ; P granisetron and ondansetron are safe and effective for the prevention of nausea and vomiting result ing from TBI . Bone Marrow Transplantation ( 2000 ) 26 , 203–210", "BACKGROUND The prevention of delayed nausea and vomiting caused by moderately emetogenic chemotherapy for cancer has not been studied systematic ally . METHODS We enrolled patients who were scheduled to receive chemotherapy for the first time in a double-blind , r and omized , multicenter study . All the patients received ondansetron combined with dexamethasone for prophylaxis against emesis that might occur within 24 hours after the start of chemotherapy ( acute emesis ) . They were then divided into two groups : patients who did not have either vomiting or moderate-to-severe nausea ( the low-risk group ) and patients who had one or both ( the high-risk group ) . Patients in the low-risk group were then r and omly assigned to one of the following regimens , given on days 2 through 5 after the start of chemotherapy : oral placebo , 4 mg of dexamethasone given orally twice daily , or 8 mg of ondansetron in combination with 4 mg of dexamethasone , given orally twice daily . Patients in the high-risk group were r and omly assigned to receive oral dexamethasone alone or in combination with ondansetron at the same doses as those used in the low-risk group . RESULTS Among the 618 patients in the low-risk group , there was a complete absence of both delayed vomiting and moderate-to-severe nausea in 91.8 percent of those who received ondansetron combined with dexamethasone , 87.4 percent of those who received dexamethasone alone , and 76.8 percent of those who received placebo . The proportions of patients who were protected by dexamethasone combined with ondansetron or by dexamethasone alone were significantly greater than the proportion protected by placebo ( P 87 patients in the high-risk group , complete protection was achieved in 40.9 percent of those treated with ondansetron and dexamethasone and in 23.3 percent treated with dexamethasone alone ( P not significant ) . CONCLUSIONS The best way to prevent delayed nausea and vomiting in patients receiving moderately emetogenic chemotherapy is to control these complications within the first 24 hours after the start of chemotherapy . Dexamethasone alone provides adequate protection against delayed emesis in patients at low risk ( those who have not had acute emesis )", "Chronic nausea occurs in most patients with advanced cancer . This study was done to assess the antiemetic effects of dexamethasone in patients with chronic nausea refractory to metoclopramide . Secondary outcomes included appetite , fatigue , and pain . Fifty-one patients who had nausea ( > or = 3/10 on a 0 - 10 scale ) for > or = 2 weeks despite 48 hours of oral metoclopramide therapy ( 40 - 60 mg/day ) were enrolled . Patients received 20 mg/day dexamethasone ( DM ) orally ( n = 25 ) or placebo ( n = 26 ) for severe nausea in addition to metoclopramide ( 60 mg/day orally ) . At baseline the mean nausea intensity ratings in the DM and placebo groups were 8.0 and 7.4 . At Day 8 they were 2.1 and 2.0 , respectively . At Day 3 and Day 8 , the mean difference in nausea intensity for the DM and placebo groups was 4.5 and 2.9 ( P = 0.16 ) and 5.9 and 5.7 ( P = 0.85 ) , respectively . Improvement in appetite and fatigue were observed on Day 3 and Day 8 in both groups as compared with the baseline . Pain , vomiting , well-being , and quality of life remained unchanged in both groups at both times . We conclude that DM was not superior to placebo in the management of chronic nausea in our patients with advanced cancer", "BACKGROUND Palonosetron is a second-generation 5-hydroxytryptamine 3 ( 5-HT(3))-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting ( CINV ) in patients receiving moderately emetogenic chemotherapy , and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy . In this phase III , multicentre , r and omised , double-blind , double-dummy , stratified , parallel-group , active-comparator trial , we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting , both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy . METHODS Between July 5 , 2006 , and May 31 , 2007 , 1143 patients with cancer who were receiving highly emetogenic chemotherapy ( ie , cisplatin , or an anthracycline and cyclophosphamide combination [ AC/EC ] ) were recruited from 75 institutions in Japan , and r and omly assigned to either single-dose palonosetron ( 0.75 mg ) , or granisetron ( 40 microg/kg ) 30 min before chemotherapy on day 1 , both with dexamethasone ( 16 mg intravenously ) on day 1 followed by additional doses ( 8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC ) on days 2 and 3 . A non-deterministic minimisation method with a stochastic-biased coin was applied to the r and omisation of patients . Covariates known to effect emetic risk , such as sex , age , and type of highly emetogenic chemotherapy , were used as stratification factors of minimisation to ensure balance between the treatment groups . Primary endpoints were the proportion of patients with a complete response ( defined as no emetic episodes and no rescue medication ) during the acute phase ( 0 - 24 h postchemotherapy ; non-inferiority comparison with granisetron ) and the proportion of patients with a complete response during the delayed phase ( 24 - 120 h postchemotherapy ; superiority comparison with granisetron ) . The non-inferiority margin was predefined in the study protocol as a 10 % difference between groups in the proportion of patients with complete response . The palonosetron dose of 0.75 mg was chosen on the basis of two dose-determining trials in Japanese patients . All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses ( modified intention to treat ) . This trial is registered with Clinical Trials.gov , number NCT00359567 . FINDINGS 1114 patients were included in the efficacy analyses : 555 patients in the palonosetron group and 559 patients in the granisetron group . 418 of 555 patients ( 75.3 % ) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients ( 73.3 % ) in the granisetron group ( mean difference 2.9 % [ 95 % CI -2.70 to 7.27 ] ) . During the delayed phase , 315 of 555 patients ( 56.8 % ) had complete response in the palonosetron group compared with 249 of 559 patients ( 44.5 % ) in the granisetron group ( p constipation ( 97 of 557 patients [ 17.4 % ] in the palonosetron group vs 88 of 562 [ 15.7 % ] in the granisetron group ) and raised concentrations of serum aminotransferases ( aspartate aminotransferase : 24 of 557 [ 4.3 % ] vs 34 of 562 [ 6.0 % ] ; alanine aminotransferase : 16 of 557 [ 2.9 % ] vs 33 of 562 [ 5.9 % ] ) ; no grade 4 main treatment-related adverse events were reported . INTERPRETATION When administered with dexamethasone before highly emetogenic chemotherapy , palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase , with a comparable safety profile for the two treatments . FUNDING Taiho Pharmaceutical ( Tokyo , Japan )", "Aprepitant is a neurokinin1 receptor antagonist that , in combination with a corticosteroid and a 5‐hydroxytryptamine3 receptor antagonist , has been shown to be very effective in the prevention of chemotherapy‐induced nausea and vomiting . At doses used for the management of chemotherapy‐induced nausea and vomiting , aprepitant is a moderate inhibitor of cytochrome P4503A4 and may be used in conjunction with corticosteroids such as dexamethasone and methylprednisolone , which are substrates of cytochrome P4503A4 . The effects of aprepitant on the these 2 corticosteroids were evaluated", "BACKGROUND Emesis and nausea are common adverse effects of chemotherapy . Consequences include dehydration , acute renal failure , esophageal rupture , electrolyte imbalance and undernutrition , among others . First-generation 5-HT3 antagonists significantly reduce these symptoms but are expensive and require administration every 8 - 12h . Palonosetron , a second generation 5-HT3 antagonist has proven better results in adult population s. Other benefits include a one-dose administration with effect for up to 7 days and a lower treatment cost . No clinical studies have evaluated the safety and efficacy of palonosetron in children . METHODS Prior to every course , patients were r and omized to receive palonosetron or ondansetron . Patients or guardians recorded the number of emetic events and the intensity of nausea over a 7-day period . They also reported any possible adverse effects . Statistical analysis included chi(2 ) test , relative risk , and Student 's t test . RESULTS Fifty courses were analyzed for each group . There was a significant reduction in emesis on the first 3 days and in the intensity of nausea in the first four days in the palonosetron group . There was an increased risk of presenting emesis and nausea in the acute phase when treated with ondansetron . No adverse effects were reported . The cost of treatment was also reduced when using palonosetron . CONCLUSIONS Palonosetron is a safe and effective antiemetic treatment in children , as well as being cost effective", "We design ed a multicenter , double-blind r and omized study to determine the safety and antiemetic effectiveness of intravenous ( IV ) methylprednisolone ( P ) combined with high-dose IV metoclopramide ( MTC ) v MTC alone in 200 untreated cancer patients receiving cisplatin chemotherapy . One hundred eighty-five patients were evaluable for treatment efficacy . MTC plus P was significantly superior to MTC alone in reducing the number and length of vomiting episodes ( P = .001 and P = .0008 , respectively ) and the maximal intensity of nausea ( P = .0124 with a score system ; P = .0155 with a linear analogue scale ) and length of nausea ( P = .0056 ) . The subgroup with a major incidence of nausea and vomiting was women , especially young women , out patients , and those treated with higher doses of cisplatin . Side effects were low and equally distributed between the two treatment groups . We conclude that MTC plus P has greater antiemetic activity than MTC alone in patients receiving cisplatin chemotherapy", "BACKGROUND The neurokinin-1 receptor antagonist aprepitant , plus a 5HT3 antagonist and corticosteroid is well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in adults but has not been formally assessed in adolescents . PROCEDURE Patients age 11 - 19 years old receiving emetogenic chemotherapy were r and omized 2:1 to aprepitant triple therapy ( aprepitant [ A ] 125 mg p.o . , dexamethasone [ D ] 8 mg p.o . , and ondansetron [ O ] 0.15 mg/kg i.v . t.i.d . day 1 ; A 80 mg , D 4 mg , and O 0.15 mg/kg t.i.d . day 2 ; A 80 mg and D 4 mg day 3 ; and D 4 mg day 4 ) or a control regimen ( D 16 mg and O 0.15 mg/kg t.i.d . day 1 ; D 8 mg and O 0.15 mg/kg t.i.d . day 2 ; and D 8 mg days 3 and 4 ) . The primary endpoint was the difference in drug-related adverse events during and for 14 days following treatment . Efficacy and aprepitant pharmacokinetics were assessed . RESULTS Baseline characteristics were similar between aprepitant ( N = 28 ) and control ( N = 18 ) groups . Febrile neutropenia was more frequent in the aprepitant group ( 25 % vs. 11.1 % ) . Complete response ( CR ) rates were 35.7 % for aprepitant triple therapy versus 5.6 % for the control group . Mean plasma aprepitant AUC(0 - 24 hr ) and C(max ) on day 1 and mean trough concentrations on days 2 and 3 were consistently lower compared to historical data obtained from healthy adults ; however , the differences were not clinical ly significant . CONCLUSION Aprepitant triple therapy was generally well tolerated ; CR were greater with aprepitant , although not statistically significant . Pharmacokinetics suggest that the adult dosing regimen is appropriate for adolescents", "Summary Severe , debilitating nausea and vomiting are seen in almost 100 % of patients treated with cis-platinum . These side-effects can be so severe and prolonged as to preclude therapy in a large number of patients . Commonly used antiemetics have had only limited success in controlling cis-platinum-induced nausea and vomiting . Various reports have indicated benefits from steroids in this setting .We have tested a high-dose dexamethasone regimen with or without neuroleptics , which inhibits chemotherapy-induced vomiting in 50 % of patients failing with prior antiemetics and in 71 % of those who had not received prior antiemetics . This treatment was administered on an out-patient basis as it involved oral administration of the antiemetic . Neuroleptic therapy was not r and omly assigned , but the results of this pilot study suggest that it did not enhance dexamethasone 's efficacy . There were no significant side-effects due to the steroids . The antiemetic effectiveness of dexamethasone was retained through repeated courses of chemotherapy", " Thirty-three patients with lung cancer receiving 80 mg m(-2 ) cisplatin were treated with high-dose dexamethasone ( 32 mg m(-2 ) on days 1 - 3 , 16 mg m(-2 ) on day 4 and 8 mg m(-2 ) on day 5 ) combined with granisetron on day 1 and metoclopramide on days 2 - 5 . Twenty-eight ( 85 % ) patients had no nausea or vomiting on day 1 , and 16 ( 48 % ) achieved total control on days 1 - 5 with acceptable toxicity . High-dose dexamethasone for cisplatin-induced delayed emesis should be further evaluated in a phase III trial", "Nausea and vomiting are extremely common and most distressing side effects of high-dose cisplatin therapy . Cisplatin induces anticipatory and acute , as well as , delayed emesis . High doses of metoclopramide can effectively decrease the intensity of these symptoms in up to 70 % of cases . Several agents , including dexamethasone and antihistamines have been demonstrated to either increase the efficacy of metoclopramide or decrease the side effects . Lorazepam , a benzodiazepine , has both antiemetic and anxiolytic properties . It can be useful as an adjunct to metoclopramide-based therapy . We conducted a r and omized trial to evaluate the efficacy of lorazepam in managing anticipatory , acute , and delayed emesis induced by high doses of cisplatin . A total of 180 events involving cisplatin administration ( 100 mg/m2 as a 24-hour continuous infusion ) were r and omized to receive metoclopramide along with dexamethasone and clemastine with and without lorazepam . Categorical scales were utilized to document the incidence of nausea and vomiting and side effects related to antiemetic therapy . All episodes are evaluable . Lorazepam significantly reduced the incidence of anticipatory nausea and vomiting ( P acute emesis ( P = .05 ) induced by cisplatin . Delayed emesis was also decreased ; however , it was statistically significant on day 3 only ( P Side effects were few except for mild sedation and amnesia , which were significantly more common in those receiving lorazepam ( P lorazepam increases the efficacy of metoclopramide against cisplatin-induced anticipatory , acute , and delayed nausea and vomiting . This four-drug regimen may offer one of the best combinations to be utilized in comparative trials against the newly introduced serotonin antagonists", "Aprepitant is a novel neurokinin 1 ( NK1 ) antagonist that has been shown to improve control of chemotherapy‐induced nausea and vomiting ( CINV ) when added to a st and ard antiemetic regimen of a 5‐hydroxytriptamine‐3 antagonist plus a corticosteroid . The authors sought to evaluate further the efficacy and tolerability of aprepitant plus st and ard therapy in a large clinical trial", "PURPOSE In early clinical trials with patients receiving highly emetogenic chemotherapy , the neurokinin antagonist aprepitant significantly enhanced the efficacy of a st and ard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid . This multicenter , r and omized , double-blind , placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus st and ard therapy in the prevention of chemotherapy-induced nausea and vomiting ( CINV ) . PATIENTS AND METHODS Patients receiving cisplatin > or = 70 mg/m2 for the first time were given either st and ard therapy ( ondansetron and dexamethasone on day 1 ; dexamethasone on days 2 to 4 ) or an aprepitant regimen ( aprepitant plus ondansetron and dexamethasone on day 1 ; aprepitant and dexamethasone on days 2 to 3 ; dexamethasone on day 4 ) . Patients recorded nausea and vomiting episodes in a diary . The primary end point was complete response ( no emesis and no rescue therapy ) on days 1 to 5 postcisplatin , analyzed by a modified intent-to-treat approach . Treatment comparisons were made using logistic regression models . Tolerability was assessed by reported adverse events and physical and laboratory assessment s. RESULTS The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group ( 72.7 % [ n = 260 ] v 52.3 % in the st and ard therapy group [ n = 260 ] ) , as were the percentages on day 1 , and especially on days 2 to 5 ( P st and ard dual therapy , addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy", "Factors related to the prevalence , prediction , and course of anticipatory nausea ( AN ) in women ( n = 77 ) receiving adjuvant chemotherapy for breast cancer were examined . Using a prospect i ve longitudinal research design , patients were interviewed both before and after each chemotherapy infusion . Fifty‐seven percent of the patients developed AN . These patients were characterized by more severe gastrointestinal side effects following the initial infusion and greater expectations for experiencing chemotherapy‐related nausea . A more rapid development of AN was related to a history of experiencing nausea across a greater variety of situations , higher IV drug doses , and less infusion‐related anxiety at the initial infusion . Although AN occurred intermittently across treatment sessions , severity was constant . Results provided strong support for the hypothesis that classical conditioning processes are instrumental in AN acquisition . The role of anxiety in the development of AN is considered as are clinical implication s for the prevention of AN and recommendations for future research", "St and ard chemotherapy for disseminated germ-cell tumors includes a combination of cisplatin , vinblastine , and bleomycin , but this regimen produces substantial neuromuscular toxicity . In a r and omized clinical trial in 261 men with disseminated germ-cell tumors , we substituted etoposide for the vinblastine in this regimen in half the patients to compare the efficacy and toxicity of the two treatments . Among 244 patients who could be evaluated for a response , 74 percent of those receiving the regimen including vinblastine and 83 percent of those receiving the regimen including etoposide became disease-free with or without subsequent surgery ( P not significant ) . Among the 157 patients with high tumor volume , 61 percent became disease-free on the regimen that included vinblastine , as compared with 77 percent on the regimen that included etoposide ( P less than 0.05 ) . Survival among the patients who received etoposide was higher ( P = 0.048 ) . The regimens were similar in terms of myelosuppressive effects and pulmonary toxicity . However , the etoposide regimen caused substantially fewer paresthesias ( P = 0.02 ) , abdominal cramps ( P = 0.0008 ) , and myalgias ( P = 0.00002 ) . We conclude that etoposide with cisplatin and bleomycin is superior to vinblastine with cisplatin and bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and , among patients with advanced disease , better efficacy", "The nausea and vomiting experienced by one in four cancer patients in anticipation of chemotherapy is probably a learned response to treatment . To determine whether behavioral approaches for altering learned responses might be useful treatments for these symptoms , we compared the effects of \" systematic desensitization \" ( a behavioral treatment in which relaxation is learned as a response to situations in which patients have had anticipatory nausea and vomiting ) with those of counseling and of no treatment . Sixty ambulatory cancer patients with anticipatory nausea and vomiting before their third and fourth chemotherapy treatments were r and omized equally to the three groups . Significantly more patients receiving desensitization reported no anticipatory nausea before their fifth and sixth chemotherapy treatments than patients given counseling ( P less than 0.05 ) or no treatment ( P less than 0.01 ) . Desensitized patients also reported significantly less severe anticipatory nausea ( P less than 0.01 ) and vomiting ( P less than 0.05 ) and a shorter duration of anticipatory nausea ( P less than 0.01 ) . We conclude that systematic desensitization appears to have an antiemetic effect in cancer patients who receive chemotherapy , and may be useful in the management of these problems", "The efficacy of H2‐receptor antagonists in functional dyspepsia is equivocal and the therapeutic place of proton pump inhibitors in functional dyspepsia is unknown", " One hundred and seventy-five patients selected at r and om were prospect ively studied . All patients were assessed at least after the first cycle of treatment by a self-report question naire which covered the occurrence of nausea and vomiting 24 before chemotherapy , as well as information regarding 22 clinical parameters . Forty-six ( 26 % ) patients developed anticipatory nausea . ' Intolerable ' posttreatment vomiting and age under 45 were statistically significant parameters ( p less than 0.05 ) in the multivariate analysis . Twenty-one ( 12 % ) of the 175 patients experienced anticipatory vomiting . Three variables , age under 45 , ' intolerable ' posttreatment vomiting and more than three cycles of treatment were found to be significant ( p less than 0.05 ) . The relative risk of developing anticipatory nausea and vomiting according to combination of significant clinical predictors in the multivariate analysis is proposed . Therefore recognition of these clinical predictors may serve as a marker for patients with high risk of presenting anticipatory nausea and vomiting , who may benefit from prophylactic behavioral approaches" ]

[ "In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias", "BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe", "The value of prophylactic oral gentamicin sulfate therapy in the prevention of necrotizing enterocolitis ( NEC ) was evaluated in a group of 42 high-risk neonates over a four-month period in a r and omized , double-blind controlled trial . Twenty babies in the treatment group received 2.5 mg/kg of gentamicin sulfate every six hours for one week after birth , and 22 babies received dextrose- and -water placebo in an equivalently small volume . None of the 20 gentamicin-treated babies developed NEC . Four of the control babies did . Two of these babies died , and their diagnosis was pathologically confirmed . This difference in the incidence of NEC between the treatment and control group was significant at the .05 level . These results support the prophylactic use of orally given gentamicin for selected babies at high risk for NEC , particularly those born prematurely and those who have a history of perinatal asphyxia or umbilical artery catheterization or both . Continued surveillance for changes in antimicrobial sensitivity patterns is recommended", "Small premature infants are often hypochlorhydric , and frequently their stomachs are colonized by enteric , gram-negative bacteria . We tested a hypothesis that gastric pH affected the colonization of the stomach with enteric bacteria and that this colonization was causally related to the risk or severity of necrotizing enterocolitis . A prospect i ve , double-blind study was conducted that compared a group of infants supplemented with 0.01–0.02 ml of 1 N HCl/ml of milk to a group with a similar supplement of water . Gastric pH , gastric enteric bacteria counts , and the incidence and severity of necrotizing enterocolitis were monitored . The median gastric pH of the HCl-supplemented group was lower ( 3.0 ) than controls ( 4.0 ) throughout the study ( p The gastric enteric bacterial colonization rate and the quantitative bacterial counts were strongly correlated with gastric pH over 4 ( p Somatic growth rates in infants in the HCl-supplemented group were equal to , or exceeded , those in the control group . There was 1 case of necrotizing entero-colitis among the 34 infants in the HCl-supplemented group and 8 cases among the 34 in the control group ( p = 0.02 ) . It appears that acidifying the feedings of small premature infants to a pH low enough to inhibit bacterial proliferation in the stomach significantly lowers the risk of necrotizing enterocolitis ", "In a r and omized clinical trial , we evaluated the efficacy of an oral immunoglobulin preparation ( 73 percent IgA and 26 percent IgG ) in reducing the incidence of necrotizing enterocolitis in infants of low birth weight for whom breast milk from their mothers was not available . A total of 434 infants weighing between 800 and 2000 g were eligible for entry in the study . Of these , 255 were withdrawn - 234 during the first week of the study because breast milk from their mothers became available ( 123 in the treatment group and 111 in the control group ) , and 21 because of violations of protocol or because breast milk became available after the first week . The duration of follow-up was 28 days . Among the infants for whom breast milk did not become available during the study , there were no cases of necrotizing enterocolitis among the 88 receiving oral IgA-IgG , as compared with six cases among the 91 control infants ( P = 0.0143 ) . Of the infants withdrawn from the study , two assigned to the control group had necrotizing enterocolitis . We conclude that the oral administration of IgA-IgG may prevent the development of necrotizing enterocolitis in low-birth-weight infants", "PURPOSE Low birth weight is the most important risk factor for developing necrotizing enterocolitis ( NEC ) . We aim ed to establish birth weight-based benchmarks for in-hospital mortality in neonates with NEC . METHODS Five hundred eleven centers belonging to the Vermont Oxford Network prospect ively evaluated 71,808 neonates with birth weight of 501 to 1500 g between January 2005 and December 2006 . The primary outcome variable was in-hospital mortality . RESULTS Birth weight was divided into 4 categories by 250-g increments . The NEC risk ( P mortality ( P Necrotizing enterocolitis was associated with a significant odds ratio for death for each category ( P NEC mortality increased with higher birth weight category ( category 1 = 1.6 vs category 4 = 9.9 ; P in-hospital mortality rate of neonates with NEC remains high and is significantly related to birth weight category . Although the risk and absolute mortality of NEC decrease with higher birth weight , the odds ratios indicate that NEC has a relatively greater impact upon mortality at higher birth weight . These data afford birth weight-based mortality benchmarks that may be useful in assessing single center NEC outcomes and facilitating comparisons between centers", "In a prospect i ve multicentre study on 926 preterm infants formally assigned to their early diet , necrotising enterocolitis developed in 51 ( 5.5 % ) . Mortality was 26 % in stringently confirmed cases . In exclusively formula-fed babies confirmed disease was 6 - 10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk . Pasteurised donor milk seemed to be as protective as raw maternal milk . Among babies born at more than 30 weeks ' gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk ; it was 20 times more common in those fed formula only . Other risk factors included very low gestational age , respiratory disease , umbilical artery catheterisation , and polycythaemia . In formula-fed but not breast-milk-fed infants , delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis . With the fall in the use of breast milk in British neonatal units , exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year . About 100 of these infants would die", "Necrotizing enterocolitis ( NEC ) represents one of the major causes of morbidity in low-birth-weight ( LBW ) preterm infants . This r and omized clinical trial evaluated the efficacy of an oral immunoglobulin preparation ( containing monomeric IgG in a concentration of 90 % ) in reducing the incidence of NEC in infants of LBW for whom maternal breast milk was not available . One hundred and thirty-two formula-fed newborns with a birth weight less than or equal to 1,500 g or a gestational age less than or equal to 34 weeks were r and omly studied . Five hundred mg of IgG pro die , subdivided into 5 doses , were given orally to the test group of 65 neonates during the first 2 weeks of life . Although the number of infants included in this group is limited , the results of this study are encouraging : during the first 15 days after birth , none of the subjects developed NEC , while 4 cases were confirmed in the untreated control group . It , therefore , seems possible that oral monomeric IgG administration may prevent the development of NEC in LBW infants", "We conducted a prospect i ve r and omized trial to compare the efficacy of oral gentamicin versus oral IgA‐IgG for the prophylaxis of necrotizing enterocolitis ( NEC ) ; 200 newborns considered at high risk for NEC were assigned to group A ( oral IgA‐IgG , n= 100 ) or group B ( oral Gentamicin , n= 100 ) . NEC was diagnosed in 13 cases in group A and in 1 case in group B between the 3rd and 16th days of life . Surgical treatment was necessary in 3 cases ( 2 in group A ) . All infants survived . We conclude that oral gentamicin is more effective than oral IgA‐IgG in the prevention of NEC in infants at high risk", "Objective . We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . Patients and Methods . A prospect i ve , masked , r and omized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW ( the trial . They were r and omized into 2 groups after parental informed consents were obtained . The infants in the study group were fed with Infloran ( Lactobacillus acidophilus and Bifidobacterium infantis ) with breast milk twice daily until discharged . Infants in the control group were fed with breast milk alone . The clinicians caring for the infants were blinded to the group assignment . The primary outcome was death or NEC ( ≥ stage 2 ) . Results . Three hundred sixty-seven infants were enrolled : 180 in the study group and 187 in the control group . The demographic and clinical variables were similar in both groups . The incidence of death or NEC ( ≥ stage 2 ) was significantly lower in the study group ( 9 of 180 vs 24 of 187 ) . The incidence of NEC ( ≥ stage 2 ) was also significantly lower in the study when compared with the control group ( 2 of 180 vs 10 of 187 ) . There were 6 cases of severe NEC ( Bell stage 3 ) in the control group and none in the study group . None of the positive blood culture grew Lactobacillus or Bifidobacterium species . Conclusion . Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants", "BACKGROUND Neonatal necrotising enterocolitis is a serious , commonly fatal disease in premature neonates . Although feeding with expressed breast milk and other good nursery practice s are partly protective , preventive measures are needed . Treating neonates enterally with a mixture of human IgA and IgG , prepared from donated blood , has been cl aim ed to protect against necrotising enterocolitis . However , no IgA preparation is available in Australia . Our aim , therefore , was to identify whether or not enteral IgG could prevent the disorder . METHODS We did a multicentre , double-blind , placebo- controlled trial . We r and omly assigned 768 infants to receive human IgG 1200 mg/kg daily , and 761 to receive placebo , for up to 28 days . Treatment began at the same time as enteral feeding . The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial , and any deaths that result ed from the disorder in the treatment and placebo groups . Analysis was on an intention-to-treat basis . FINDINGS 43 infants developed definite necrotising enterocolitis in the IgG group , ten of whom died . In the placebo group , 41 infants contracted the disorder and six died ( p=0.47 ) . 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis ( p=0.14 ) . INTERPRETATION Supplementation of enteral feeds with human IgG does not reduce necrotising enterocolitis" ]

[ "Abstract : The aim of this placebo-controlled , r and omized , single-masked study was to establish the effects of a 10-week ambulatory exercise programme for osteoporotic patients on pain , use of analgesics , functional status , quality of life , balance and muscle strength . Fifty-three ambulatory postmenopausal women with at least one spinal crush fracture and pains within the last 3 years were r and omized for physiotherapeutic training twice a week for 10 weeks or no training . The training included general training of balance and muscle strength , with stabilization of the lumbar spine . The participants were tested at baseline , week 5 and week 10 with a balance test , muscle strength test and question naires on pain , use of analgesics , functional status and quality of life . Twelve weeks after the supervised training had finished ( week 22 ) they answered the same question naires . The study groups were comparable at baseline . The training group had a significant reduction in use of analgesics ( p= 0.02 ) and pain level ( p= 0.01 ) during the training period . Distribution of functional score improved ; the improvement was reduced at week 22 . Quality of life score improved significantly throughout the study ( p= 0.0008 ) , even after week 22 . Balance improved non-significantly ( p= 0.08 ) . Quadriceps muscle strength improved significantly after 5 weeks ( p= 0.04 ) . Back extensor muscle strength improved almost significantly ( p= 0.09 ) . In conclusion , this training programme for osteoporotic patients improved balance and level of daily function and decreased experience of pain and use of analgesics . Quality of life was improved even beyond the active training period", "Introduction : Specific pharmacological treatment reduces the incidence of fractures significantly in patients with osteoporosis . Unfortunately , compliance with such therapy is low in clinical practice and is inversely related to educational level . We hypothesized that patients ' knowledge of osteoporosis may be increased by a group-based multidisciplinary education programme . Methods : Three hundred patients , aged 45—81 years , recently diagnosed with osteoporosis and started on specific treatment , were r and omized to either the \" school ' ' or \" control ' ' group . Teaching was performed by nurses , physiotherapists , dieticians , and doctors , and design ed to increase the patient 's empowerment . The patient 's knowledge of osteoporosis was tested at study entry and at 3 months using a vali date d question naire . Results : At study entry , no differences in age or score ( 22 ( 18—24 ) ( median ( 25—75 percentiles ) ) vs. 22 ( 18—24 ) ) were seen between the school and control groups . The change in knowledge during the study , however , differed significantly between the two groups ( p the increase in knowledge score correlated inversely with the level of education ; that is , the lower the education level , the higher the gain in knowledge during the course ( Rho=-0.25 , p group-based multidisciplinary education programme significantly increases patients ' knowledge of the disease", "OBJECTIVE To examine the effect of community-based nutrition education intervention on calcium intake and bone mass in Vietnamese postmenopausal women . DESIGN A controlled trial was conducted in two groups as intervention and control . The intervention group was given nutrition education during 18 months to improve calcium intake , while the control subjects had the usual diet . Calcium intake and bone mass were evaluated every 6 months . Bone mass was assessed by speed of sound ( SOS ) at calcaneus , referred to as quantitative ultrasound measurement . Anthropometric indices and serum parathyroid hormone ( PTH ) were determined at baseline and at the end of intervention . SETTING Two rural communes of Hai Duong province located in the Red River Delta in Vietnam . SUBJECTS A total of 140 women aged 55 - 65 years , who were more than 5 years postmenopausal and with low calcium intake ( After 18 months of intervention , 108 women completed the study . RESULTS Calcium intake in the intervention group had increased significantly ( P SOS values were not changed significantly in the intervention subjects while it decreased significantly by 0.5 % in the controls ( P serum PTH by 12 % ( P serum PTH by 32 % ( P Nutrition education intervention was effective in improving calcium intake and retarding bone loss in the studied subjects", "OBJECTIVE : To define the effects of therapeutic exercise on bone density and back complaints . METHODS : A r and omised controlled trial with parallel groups was conducted in an outpatient clinic , Medical School , University of Vienna . Ninety two sedentary post-menopausal women with back problems were r and omly allocated to either exercise ( groups 1 and 2 ) or control ( group 3 , no exercise , n = 31 ) ; the exercise group was retrospectively subdivided into compliant ( group 1 , n = 27 ) and not fully compliant patients ( group 2 , n = 34 ) . Regular , initially supervised therapeutic exercise aim ed at restoring biomechanical function was performed for four years . Bone density in the forearm was measured by single photon absorptiometry at entry and after four years ; subjective back complaints were documented . RESULTS : A significant decrease in bone density was observed in groups 2 and 3 ; no change was noted in group 1 ; back complaints decreased in group 1 only . CONCLUSIONS : Sedentary postmenopausal women may benefit from regular long term therapeutic exercise in terms of subjective back complaints and slowed loss of bone mass", "Alp A , Kanat E , Yurtkuran M : Efficacy of a self-management program for osteoporotic subjects . Am J Phys Med Rehabil 2007;86:633–640 . Objective : This study is based on whether the self-management program choices For Better Bone Health is effective to promote behavioral strategies for improving bone health , life quality , pain perception , physical function , and balance in osteoporotic subjects . Design : In this single-blind , r and omized controlled study , a total of 50 sedentary women with postmenopausal and idiopathic osteoporosis were selected from the out patients of Atatürk Balneotherapy and Rehabilitation Center according to their physical activity level and T scores of dual-energy x-ray absorptiometry as the inclusion criteria . Fifty sedentary women with BMD T scores of −2.5 or lower were r and omized into two groups ( self-management group : group 1 ; and control group : group 2 ) and enrolled in a 6-mo study . Participants attended self-management class once a week for 5 wks . Evaluations were done at baseline , at the end of the fifth week , and at the sixth month . Pain-intensity evaluation by Visual Analogue Scale ( VAS ) , life- quality assessment s by SF-36 , balance testing by Sensitized Romberg Test ( SRT ) , and functional assessment by Timed Sit to St and test ( TSS ) and a simple question naire were the outcome measures . Results : When the groups were compared by change scores and percentages of change , improvements observed in pain intensity by VAS ( P , SF-36 Physical Function ( P , SF-36 Physical Role Limitations ( P 0.001 ) , SF-36 Social Function ( P ) , SF-36 Mental Health ( P , SF-36 Vitality ( P ) , SF-36 Pain ( P 0.001 ) , SF-36 General Health Perceptions ( P ) , SF-36 Emotional Role Limitations ( P , SRT eyes open ( P SRT eyes closed ( P , and TSS ( P medications and dietary calcium intake . Fifty-seven percent of them formed personal plans for preventing traumas , whereas 8 % of the subjects in group 2 experienced new falls but no fractures . Conclusion : It is determined that the self-management class led to improvements in functional , balance , and life- quality outcomes and to reductions in pain perception", "OBJECTIVE To evaluate the effects of a 3-month home-based physical therapy ( PT ) program for patients with hip fracture after surgery . DESIGN R and omized controlled trial . SETTING Home . PARTICIPANTS Twenty-five patients recently discharged from an acute orthopedic department . INTERVENTIONS Patients were r and omized to the home-based PT group ( n=13 ) , where they received home-based PT 8 times from discharge to month 3 postdischarge , or to the control group ( n=12 ) . The home-based PT program included exercises for muscle strengthening , range of motion ( ROM ) , balance , and functional training . Patients in the control group were instructed to practice the exercise program given at bedside before discharge . MAIN OUTCOME MEASURES Patients were evaluated for hip ROM , strength , walking velocity , Harris hip score , and health-related quality of life ( HRQOL ) at the week of discharge and at 1 , 3 , and 6 months after discharge . RESULTS The baseline characteristics showed no difference between the 2 groups . Harris score of the home-based PT group progressed from 58.6+/-8.5 to 90.1+/-5.4 at month 3 , whereas Harris score of the control group progressed from 54.6+/-14.5 to 77.4+/-10.0 ( P Scores of the psychologic domain of HRQOL for the home-based PT group were significantly better at month 1 ( P physical domain score of the home-based PT group was also significantly better ( P Home-based PT programs could help patients regain function and HRQOL earlier", "BACKGROUND Exercise programs improve balance , strength and agility in elderly people and thus may prevent falls . However , specific exercise programs that might be widely used in the community and that might be \" prescribed \" by physicians , especially for patients with osteoporosis , have not been evaluated . We conducted a r and omized controlled trial of such a program design ed specifically for women with osteoporosis . METHODS We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise . Women who agreed to participate were r and omly assigned to participate in a twice-weekly exercise class or to not participate in the class . We measured baseline data and , 20 weeks later , changes in static balance ( by dynamic posturography ) , dynamic balance ( by a timed figure-eight run ) and knee extension strength ( by dynamometry ) . RESULTS Of 93 women who began the trial , 80 completed it . Before adjustment for covariates , the intervention group tended to have greater , although nonsignificant , improvements in static balance ( mean difference 4.8 % , 95 % confidence interval [ CI ] -1.3 % to 11.0 % ) , dynamic balance ( mean difference 3.3 % , 95 % CI -1.7 % to 8.4 % ) and knee extension strength ( mean difference 7.8 % , 95 % CI -5.4 % to 21.0 % ) . Mean crude changes in the static balance score were -0.85 ( 95 % CI -2.91 to 1.21 ) for the control group and 1.40 ( 95 % CI -0.66 to 3.46 ) for the intervention group . Mean crude changes in figure-eight velocity ( dynamic balance ) were 0.08 ( 95 % CI 0.02 to 0.14 ) m/s for the control group and 0.14 ( 95 % CI 0.08 to 0.20 ) m/s for the intervention group . For knee extension strength , mean changes were -0.58 ( 95 % CI -3.02 to 1.81 ) kg/m for the control group and 1.03 ( 95 % CI -1.31 to 3.34 ) kg/m for the intervention group . After adjustment for age , physical activity and years of estrogen use , the improvement in dynamic balance was 4.9 % greater for the intervention group than for the control group ( p = 0.044 ) . After adjustment for physical activity , cognitive status and number of fractures ever , the improvement in knee extension strength was 12.8 % greater for the intervention group than for the control group ( p = 0.047 ) . The intervention group also had a 6.3 % greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis , but this difference was not significant ( p = 0.06 ) . INTERPRETATION Relative to controls , participants in the exercise program experienced improvements in dynamic balance and strength , both important determinants of risk for falls , particularly in older women with osteoporosis", "CONTEXT Hip fractures are common in the elderly , and despite st and ard rehabilitation , many patients fail to regain their prefracture ambulatory or functional status . OBJECTIVE To determine whether extended outpatient rehabilitation that includes progressive resistance training improves physical function and reduces disability compared with low-intensity home exercise among physically frail elderly patients with hip fracture . DESIGN , SETTING , AND PATIENTS R and omized controlled trial conducted between August 1998 and May 2003 among 90 community-dwelling women and men aged 65 years or older who had had surgical repair of a proximal femur fracture no more than 16 weeks prior and had completed st and ard physical therapy . INTERVENTION Participants were r and omly assigned to 6 months of either supervised physical therapy and exercise training ( n = 46 ) or home exercise ( control condition ; n = 44 ) . MAIN OUTCOME MEASURES Primary outcome measures were total scores on a modified Physical Performance Test ( PPT ) , the Functional Status Question naire physical function subscale ( FSQ ) , and activities of daily living scales . Secondary outcome measures were st and ardized measures of skeletal muscle strength , gait , balance , quality of life , and body composition . Participants were evaluated at baseline , 3 months , and 6 months . RESULTS Changes over time in the PPT and FSQ scores favored the physical therapy group ( P = .003 and P = .01 , respectively ) . Mean change ( SD ) in PPT score for physical therapy was + 6.5 ( 5.5 ) points ( 95 % confidence interval [ CI ] , 4.6 - 8.3 ) , and for the control condition was + 2.5 ( 3.7 ) points ( 95 % CI , 1.4 - 3.6 points ) . Mean change ( SD ) in FSQ score for physical therapy was + 5.2 ( 5.4 ) points ( 95 % CI , 3.5 - 6.9 ) and for the control condition was + 2.9 ( 3.8 ) points ( 95 % CI , 1.7 - 4.0 ) . Physical therapy also had significantly greater improvements than the control condition in measures of muscle strength , walking speed , balance , and perceived health but not bone mineral density or fat-free mass . CONCLUSION In community-dwelling frail elderly patients with hip fracture , 6 months of extended outpatient rehabilitation that includes progressive resistance training can improve physical function and quality of life and reduce disability compared with low-intensity home exercise", "Background : Osteoporosis prevention behaviors ( OPBs ) can prevent and delay bone deterioration ; dual-energy X-ray absorptiometry ( DXA ) scan can identify osteoporosis and provide personal osteoporosis risk information that may promote prevention behaviors . Objectives : This study was design ed to estimate relationships between receiving personal knowledge of bone mineral density ( gained through DXA scan ) , general knowledge of osteoporosis , health beliefs , and the two OPBs of calcium intake and weight-bearing exercise in healthy postmenopausal women 50 to 65 years . Methods : In this longitudinal , r and omized clinical trial ( including covariates ) , receipt of personal DXA information was manipulated by r and om assignment to the experimental or control group . The remaining antecedent and outcome variable measures were collected by question naire at three time points ( initial [ T1 ; pre-DXA ] , 6 months [ T2 ] , 12 months [ T3 ] ) and by bone density assessment from 203 women over an 18-month period in 2001 - 2003 . Results : The experimental manipulation ( DXA results ) had a direct positive effect ( & bgr ; = .23 , p calcium intake at T2 , and indirectly at T3 through T2 . Women in the experimental group who were informed they had osteopenia or osteoporosis had a greater T1-T2 change in daily calcium intake than those with normal bone density ( & bgr ; = .23 , p Health beliefs and general osteoporosis knowledge predicted initial calcium and exercise levels ; there was tentative evidence that susceptibility beliefs partially mediate between DXA results and change in calcium intake . Discussion : Personal knowledge of DXA results was related significantly to increases in calcium intake in postmenopausal women , but not to exercise . Directions for further study are discussed", "Objective To assess whether osteoporosis education , with and without bone mineral density ( BMD ) testing , increases the initiation of lifestyle changes and pharmaceutical treatment to prevent osteoporosis . Design A total of 508 women , aged 54–65 , from a large managed care organization who were not on osteoporosis prevention therapy participated in an intervention study . Participants were r and omly assigned to either an education class on osteoporosis ( n = 301 ) or education plus BMD ( n = 207 ) . A control group of 187 women receiving no intervention were also surveyed to serve as comparison . Group differences and differences based on BMD test result were compared 6 months after education regarding self-reported changes in health behaviors using & khgr;2 tests and logistic regression analyses . Results Of the 508 intervention participants , 455 ( 90 % ) responded to the follow-up survey . Initiation of hormone replacement therapy was reported by 9 % , with 5 % reporting starting alendronate . More than half reported changes in diet , exercise , or calcium intake . Forty-three percent increased their vitamin D intake . There were no significant group differences in behavior except with regard to pharmaceutical therapy ; subjects with education plus BMD were three times more likely than those receiving education only to report starting hormone replacement therapy ( p = 0.004 ) . Low BMD scores were associated with increasing vitamin D intake ( p = 0.03 ) and starting medication ( p = 0.001 ) . Women in the intervention groups were significantly more likely to report modifying their diet ( p 0.001 ) , calcium ( p 0.01 ) , and vitamin D intake ( p < 0.0001 ) than women in the control group , not exposed to education . Conclusion Education regarding osteoporosis prevention seems to encourage women to make lifestyle changes . The inclusion of BMD testing enhances the likelihood that women will consider pharmaceutical therapy", "Introduction Adherence to treatment in osteoporosis remains poor . The aim of this study was to evaluate the effects of an educational leaflet on adherence to medication and to assess the association between adherence and health-related quality of life ( HRQOL ) . Methods A naturalistic , observational , multi-center , prospect i ve study of 12 months ’ follow-up was performed . Consecutive post-menopausal women aged 50 years to 86 years starting treatment with raloxifene according to daily practice were enrolled from 126 primary care offices in Spain . The women were assigned to two study groups . Group A received an educational leaflet with general information about osteoporosis ; group B followed current practice . To assess adherence to medication and HRQOL , the Morisky test and the EuroQoL question naire were administered . A total of 745 post-menopausal women ( group A , n=366 ; group B n=379 ) , with a mean age of 62 years , were included . Results Most patients in both study groups showed high adherence to raloxifene at the 3-month visit : 56.3 % vs 62.7 % for groups A and B , respectively ; this proportion at the 12-month visit was 47.4 % ( P=0.15 ) and 52.5 % ( P=0.02 ) , respectively . At baseline , “ pain/discomfort ” was the dimension showing the highest percentage of women reporting problems : 86.4 % vs 83.2 % in groups A and B , respectively ( P=0.22 ) . HRQOL improved in both groups throughout the study , with an overall mean increment in the EuroQoL visual analog scale ( EQ VAS ) of 9.2 at 12 months ( P adherence and HRQOL were weak . After receiving an educational leaflet , young post-menopausal women suffering osteoporosis did not show improvement in adherence to therapy . HRQOL improved at 12-month follow-up under treatment . Conclusion No consistent correlation between adherence and HRQOL was found", "Summary R and omized controlled study in 80 postmenopausal women with osteoporosis was conducted to investigate the effect of a home-based , simple , low-intensity exercise . Low-intensity back-strengthening exercise was effective in improving the quality of life and back extensor strength . Introduction and hypothesisBack-strengthening exercise is effective in increasing back extensor strength and decreasing risk of vertebral fractures . We hypothesized that a home-based , simple , low-intensity exercise could enhance back extensor strength and improve the quality of life and /or spinal range of motion in postmenopausal women in a short-term follow-up . Methods Eighty postmenopausal women with osteoporosis were r and omly assigned to a control group ( n = 38 ) or an exercise group ( n = 42 ) . Subjects were instructed to lift their upper trunk from a prone position antigravity and maintain the neutral position . Isometric back extensor strength , spinal range of motion , and scores for quality of life were evaluated at baseline and 4 months . Results Back extensor strength significantly increased both in the exercise group ( 26 % ) and in the control group ( 11 % ) . Scores for quality of life increased in the exercise group ( 7 % ) , whereas it remained unchanged in the control group ( 0 % ) . There was a significant difference in quality of life score between the groups ( p = 0.012 ) . Conclusions Low-intensity back-strengthening exercise was effective in improving the quality of life and back extensor strength in patients with osteoporosis", "CONTEXT Persistence with osteoporosis treatment is poor but is important for maximum benefit . OBJECTIVE The objective of the study was to assess the impact of physician reinforcement using bone turnover markers ( BTMs ) on persistence with risedronate treatment . DESIGN AND SETTING This was a 1-yr multinational prospect i ve , open-label , blinded study in 171 osteoporosis centers in 21 countries . PATIENTS A total of 2382 postmenopausal women ( 65 - 80 yr old ) with spine/hip T-score -2.5 or less or T-score -1.0 or less with a low-trauma fracture . INTERVENTION Intervention included calcium 500 mg/d , vitamin D 400 IU/d , and risedronate 5 mg/d for 1 yr . Centers were r and omized to reinforcement ( RE+ ) or no reinforcement ( RE- ) . At 13 and 25 wk , reinforcement based on urinary N-telopeptide of type I collagen change from baseline was provided to the RE+ patients using the following response categories : good ( > 30 % decrease ) , stable ( -30 % to + 30 % change ) , or poor ( > 30 % increase ) . MAIN OUTCOME MEASURES Persistence assessed with electronic drug monitors was measured . RESULTS In the overall efficacy population ( n=2302 ) , persistence was unexpectedly high and was similar for both groups ( RE- , 77 % ; RE+ , 80 % ; P=0.160 ) . A significant relationship between the type of message and persistence was observed ( P=0.017 ) . Compared with RE- , intervention based on a good BTM response was associated with a significant improvement in persistence [ hazard ratio ( HR ) 0.71 ; 95 % confidence interval ( CI ) 0.53 - 0.95 ] . Persistence was unchanged ( HR 1.02 ; 95 % CI 0.74 - 1.40 ) or lower ( HR 2.22 ; 95 % CI 1.27 - 3.89 ) when reinforcement was based on a stable or poor BTM response , respectively . Reinforcement was associated with a lower incidence of new radiologically determined vertebral fractures ( odds ratio 0.4 ; 95 % CI , 0.2 - 1.0 ) . CONCLUSIONS Reinforcement using BTMs influences persistence with treatment in postmenopausal women with osteoporosis , depending on the BTM response observed", "Summary In a cluster r and omized trial , we evaluated the effect of a multifaceted intervention ( directed at both patient and primary care physician ) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture . Compared to usual care , women in the intervention practice s were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments . Introduction Postmenopausal women with wrist fractures are at increased risk of future fragility fractures , yet they frequently do not receive evaluation and treatment for osteoporosis . We set out to evaluate a multifaceted intervention design ed to improve management of osteoporosis in older women with recent wrist fractures . Methods Cluster r and omized trial of 270 women cared for in 119 primary care practice s. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario , Canada . Family practice s were r and omly assigned to either the intervention or usual care . The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician , in addition to an educational package and letter to the women . The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture . Results The mean age of women was 69(10.9 ) years . The intervention increased the proportion of women started on osteoporosis medications ( 28 % vs. 10 % ) of controls , adjusted OR 3.45 , 95 % CI , 1.58–7.56 , p = 0.002 ) and the proportion who had a bone mineral density ( BMD ) test ( 53.3 % vs. 26 % ) of controls , OR 3.38 , 95 % CI , 1.83–6.26 , p testing and treatment rates . Conclusion A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures", "Long-term adherence and persistence with any therapy are very poor ( approximately 50 % ) . Adherence to therapy is defined as the percentage of prescribed medication taken , and persistence is defined as continuing to take prescribed medication . We examined whether monitoring by nursing staff could enhance adherence and persistence with antiresorptive therapy and whether presenting information on response to therapy provided additional benefit . In addition we evaluated the impact of monitoring on treatment efficacy . Seventy-five postmenopausal women with osteopenia were r and omized to 1 ) no monitoring , 2 ) nurse-monitoring , or 3 ) marker-monitoring . All subjects were prescribed raloxifene . At 12 , 24 , and 36 wk , the nursing staff review ed subjects in the monitored ( nurse-monitoring or marker-monitoring ) groups using a predefined protocol . The marker-monitored group were also presented a graph of response to therapy using percentage change in urinary N-telopeptide of type I collagen ( uNTX ) , a bone resorption marker , at each visit . Biological response to therapy at 1 yr was determined using the percent change in bone mineral density ( BMD ) and uNTX . Treatment adherence and persistence were assessed using electronic monitoring devices . Survival analysis showed that the monitored group increased cumulative adherence to therapy by 57 % compared with no monitoring ( P = 0.04 ) . There was a trend for the monitored group to persist with therapy for 25 % longer compared with no monitoring ( P = 0.07 ) . Marker measurements did not improve adherence or persistence to therapy compared with nurse-monitoring alone . Adherence at 1 yr was correlated with percent change in hip ( BMD ) ( r = 0.28 ; P = 0.01 ) and percent change in uNTX ( r = -0.36 ; P = 0.002 ) . In conclusion , monitoring of patients increased adherence to therapy by 57 % at 1 yr . Increased adherence to therapy increased the effectiveness of raloxifene therapy determined using surrogate end points", "This r and omized controlled trial was design ed to investigate the effect of a 6-month home-based exercise program versus control ( usual activities ) on quality of life for postmenopausal women with osteoporosis who had at least one vertebral fracture . Twelve-month assessment s of outcomes were completed to determine if women would continue exercising with minimal supervision and if benefit could be sustained . The home exercise program followed a \" lifestyle exercise \" approach where participants completed exercises 60 min per day , 3 days a week and could complete exercises in small periods of time throughout the day . Exercise activities included stretching , strength training and aerobics ( i.e. walking ) . Participants were assessed at baseline , 6 months , and 12 months using the Osteoporosis Quality of Life Question naire ( OQLQ ) , the Sickness Impact Profile ( SIP ) , a balance test , and the Timed Up And Go test . Bone mineral density was assessed at baseline and 12 months for both the lumbar spine and femoral neck . Quality of life ( OQLQ ) improved over 6 months in the exercise group compared to the control group in the domains of symptoms ( P=0.003 ) , emotion ( P=0.01 ) and leisure ( P=0.03 ) . Results from the balance test indicated a greater effect in the exercise group over 12 months ( P measures of Timed Up and Go , SIP at 6 and 12 months , and femoral neck and lumbar spine bone mineral density at 12 months . Home-based exercise with minimal supervision improves quality of life in elderly women with vertebral fractures . Future research is needed to determine if home exercise programs reduce falls and fall-related injuries in the elderly", "Objective —To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis . Methods —Static balance was measured by computerised dynamic posturography ( Equitest ) , dynamic balance by timed figure of eight run , and knee extension strength by dynamometry . Subjects were r and omised to exercise intervention ( twice weekly Osteofit classes for 10 weeks ) or control groups . Results —The outcome in 79 participants ( 39 exercise , 40 control ) who were available for measurement 10 weeks after baseline measurement is reported . After confounding factors had been controlled for , the exercise group did not make significant gains compared with their control counterparts , although there were consistent trends toward greater improvement in all three primary outcome measures . Relative to the change in control subjects , the exercise group improved by 2.3 % in static balance , 1.9 % in dynamic balance , and 13.9 % in knee extension strength . Conclusions —A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis . However , trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance", "OBJECTIVES To assess the effectiveness of a community-based falls- and -fracture nurse coordinator and multifactorial intervention in reducing falls in older people . DESIGN R and omized , controlled trial . SETTING Screening for previous falls in family practice followed by community-based intervention . PARTICIPANTS Three hundred twelve community-living people aged 75 and older who had fallen in the previous year . INTERVENTION Home-based nurse assessment of falls- and -fracture risk factors and home hazards , referral to appropriate community interventions , and strength and balance exercise program . Control group received usual care and social visits . MEASUREMENTS Primary outcome was rate of falls over 12 months . Secondary outcomes were muscle strength and balance , falls efficacy , activities of daily living , self-reported physical activity level , and quality of life ( Medical Outcomes Study 36-item Short Form Question naire ) . RESULTS Of the 3,434 older adults screened for falls , 312 ( 9 % ) from 19 family practice s were enrolled and r and omized . The average age was 81+/-5 , and 69 % ( 215/312 ) were women . The incidence rate ratio for falls for the intervention group compared with the control group was 0.96 ( 95 % confidence interval=0.70 - 1.34 ) . There were no significant differences in secondary outcomes between the two groups . CONCLUSION This nurse-led intervention was not effective in reducing falls in older people who had fallen previously . Implementation and adherence to the fall-prevention measures was dependent on referral to other health professionals working in their usual clinical practice . This may have limited the effectiveness of the interventions", "PURPOSE The purpose of this pilot study was to determine if tailored nursing interventions based on personal knowledge of bone mineral density from a dual-energy x-ray absorptiometry cause increases in knowledge of osteoporosis , health beliefs , or osteoporosis-prevention behaviors in postmenopausal women 50–65 years of age , 6 months after the intervention . METHOD The design for this pilot study was a two group quasi-experimental design . The treatment group received a tailored intervention ; the control group did not . Outcome data were gathered at 6 months after dual-energy x-ray absorptiometry . The tailored intervention was design ed and given to each woman via telephone using her dual-energy x-ray absorptiometry results and osteoporosis question naire data that addressed her knowledge of osteoporosis and osteoporosis-prevention behaviors of calcium intake , exercise , smoking , and alcohol use . A written mailed copy of the intervention followed the telephone interview . Six months after the intervention , the women were mailed another osteoporosis question naire to determine if the tailored intervention made a difference in the outcome variables . SAMPLE A total 124 women between the ages of 50 and 65 ( 101 control , 23 treatment ) comprised the sample . RESULTS There was no difference in knowledge between groups . On the average , there were significantly more perceived barriers to calcium in the tailored group ( mean = 13.48 ) than in the nontailored group ( mean = 11.55 ) ( t = 2.147 ; df = 122 ; p = .034 ) . There were significantly more perceived barriers to exercise in the tailored group ( mean = 14.39 ) than in the nontailored group ( mean = 12.21 ) ( t = .144 ; df = 122 ; p = .034 ) . Daily calcium intake increased in both the tailored and the nontailored groups . The tailored intervention increased women 's daily calcium intake from 614.28 to 1039.10 mg ( t = −2.896 ; df = 22 ; p = .008 ) . The nontailored group daily calcium intake increased from 587.91 to 916.30 mg ( t = −3.541 ; df = 100 ; p = .001 ) ; there was no significant difference between the groups . Weight-bearing exercise behaviors decreased from 96.04 minutes to 59.2 minutes in the tailored group but increased slightly in the nontailored group from 81.47 to 87.26 minutes of exercise . CONCLUSION Tailored interventions increased women 's perceived barriers to calcium and exercise . Both groups increased calcium intake . The mixed findings of increased perception of barriers to calcium and exercise and decreased exercise behaviors indicate the need for further study . This important intervention has implication s for orthopaedic nurses and healthcare professionals involved in health promotion and prevention of osteoporosis", "Background : Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis . We developed a multifaceted intervention directed at older patients with wrist fractures ( in the form of telephone-based education ) and their physicians ( in the form of guidelines endorsed by opinion leaders , supported by reminders ) to improve the quality of osteoporosis care . Methods : In a r and omized controlled trial with blinded ascertainment of outcomes , we compared our intervention with usual care ( provision of printed educational material s to patients ) . Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics ; we excluded those who were already being treated for osteoporosis . The primary outcome was bisphosphonate treatment within 6 months after the fracture . Secondary outcomes included bone mineral density testing , “ appropriate care ” ( consisting of bone mineral density testing with treatment if bone mass was low ) and quality of life . Results : We screened 795 patients for eligibility and r and omly assigned 272 to the intervention ( 137 patients ) or control ( 135 patients ) group . The median age was 60 years ; 210 ( 77 % ) of the subjects were women , and 130 ( 48 % ) reported a previous fracture as an adult . Six months after the fracture , 30 ( 22 % ) of the intervention patients , as compared with 10 ( 7 % ) of the control patients , were receiving bisphosphonate therapy for osteoporosis ( adjusted relative risk [ RR ] 2.6 , 95 % confidence interval [ CI ] 1.3–5.1 , p = 0.008 ) . Intervention patients were more likely than control patients to undergo bone mineral density testing ( 71/137 [ 52 % ] v. 24/135 [ 18 % ] ; adjusted RR 2.8 , 95 % CI 1.9–4.2 , p receive appropriate care ( 52/137 [ 38 % ] v. 15/135 [ 11 % ] ; adjusted RR 3.1 , 95 % CI 1.8–5.3 , p died , and 4 others experienced recurrent fracture . Interpretation : A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis . Nevertheless , more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture , which suggests that additional strategies should be explored . ( Clinical Trials.gov trial register no. NCT00152321 .", "OBJECTIVE To evaluate the potential benefits of programmed Tai Chi Chun ( TCC ) exercise on the weight-bearing bones of early postmenopausal women . DESIGN Age-matched and r and omized prospect i ve intervention . SETTING University medical school . PARTICIPANTS One hundred thirty-two healthy postmenopausal women ( mean age , 54.0+/-3.5y ) within 10 years of menopause onset were recruited and r and omized into the TCC exercise group ( n=67 ) or the sedentary control group ( n=65 ) . INTERVENTION Supervised TCC exercise was performed by the TCC group for 45 minutes a day , 5 days a week , for 12 months ; control subjects retained a sedentary life style . Main outcome measures Bone mineral density ( BMD ) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography ( pQCT ) . All BMD measurements were repeated after 12 months in both groups . Fracture rate was also documented . RESULTS Baseline measurements showed homogeneity in age , anthropometric variables , and menstruation status between the TCC and control groups . Exactly 81.6 % of the subjects in the TCC group and 83.1 % of subjects in the control group completed the 12-month follow-up study . BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites , but with a reportedly slower rate in the TCC group . A significant 2.6- to 3.6-fold retardation of bone loss ( P fracture cases were documented during follow-up , including 3 subjects in the control group and 1 in the TCC group . CONCLUSIONS This is the first prospect i ve and r and omized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women . Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture", "BACKGROUND Patients who survive hip fracture are at high risk of recurrent fractures , but rates of osteoporosis treatment 1 year after sustaining a fracture are less than 10 % to 20 % . We have developed an osteoporosis case manager intervention . The case manager educated patients , arranged bone mineral density tests , provided prescriptions , and communicated with primary care physicians . The intervention was compared with usual care in a r and omized controlled trial . METHODS We recruited from all hospitals that participate in the Capital Health system ( Alberta , Canada ) , including patients 50 years or older who had sustained a hip fracture and excluding those who were receiving osteoporosis treatment or who lived in a long-term care facility . Primary outcome was bisphosphonate therapy 6 months after fracture ; secondary outcomes included bone mineral density testing , appropriate care ( bone mineral density testing and treatment if bone mass was low ) , and intervention costs . RESULTS We screened 2219 patients and allocated 220 , as follows : 110 to the intervention group and 110 to the control group . Median age was 74 years , 60 % were women , and 37 % reported having had previous fractures . Six months after hip fracture , 56 patients in the intervention group ( 51 % ) were receiving bisphosphonate therapy compared with 24 patients in the control group ( 22 % ) ( adjusted odds ratio , 4.7 ; 95 % confidence interval , 2.4 - 8.9 ; P Bone mineral density tests were performed in 88 patients in the intervention group ( 80 % ) vs 32 patients in the control group ( 29 % ) ( P bone mineral density testing , 25 ( 21 % ) had normal bone mass . Patients in the intervention group were more likely to receive appropriate care than were patients in the control group ( 67 % vs 26 % ; P intervention cost was $ 50.00 per patient . CONCLUSION For a modest cost , a case manager was able to substantially increase rates of osteoporosis treatment in a vulnerable elderly population at high risk of future fractures" ]

[ "Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as \" feasibility \" or \" vanguard \" studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format", "Feasibility and pilot studies play an important role in the preliminary planning of a proposed full-size r and omized clinical trial ( RCT ) . In essence , feasibility studies are used to help develop trial interventions or outcome measures , whereas pilot studies replicate , in miniature , a planned full-size RCT . However , the terms used for these preliminary studies are sometimes considered synonymous , and in practice may overlap considerably or be combined . The important issue is not the distinction between these : the important distinction is between such preliminary studies and a proper RCT . J Orthop Sports Phys Ther 2014;44(8):555–558 .", "Many factors can affect the successful implementation and validity of intervention studies . A primary purpose of feasibility and pilot studies is to assess the potential for successful implementation of the proposed main intervention studies and to reduce threats to the validity of these studies . This article describes a typology to guide the aims of feasibility and pilot studies design ed to support the development of r and omized controlled trials and provides an example of the studies underlying the development of one rehabilitation trial . The purpose of most feasibility and pilot studies should be to describe information and evidence related to the successful implementation and validity of a planned main trial . Null hypothesis significance testing is not appropriate for these studies unless the sample size is properly powered . The primary tests of the intervention effectiveness hypotheses should occur in the main study , not in the studies that are serving as feasibility or pilot studies", "BACKGROUND People with Multiple Sclerosis ( PwMS ) are less physically active than the general population and pragmatic approaches design ed to equip them with the skills and confidence to participate in long-term physical activity are required . OBJECTIVE The objective of this study was to determine the feasibility of a pragmatic exercise intervention in PwMS . METHODS A voluntary sample of 30 PwMS ( male n = 4 , female n = 26 ; mean age = 40 years ; range = 24 - 49 years ) , with mild to moderate disability ( EDSS ≤ 5.5 ) , were recruited from eligible participants attending outpatient clinics . A total of 28 participants were r and omised to a 10 week pragmatic exercise intervention ( 2 × supervised and 1 × home-based session per week ) or usual care . Clinical , functional and quality of life ( MSQoL-54 ) outcomes were assessed at baseline , immediately and 3 months after the intervention . RESULTS Attrition was low ( 2 participants lost to immediate follow-up and 4 participants lost to 3 month follow-up ) , with high compliance rates ( > 75 % of all sessions ) . The intervention group achieved progression of exercise volume ( 24.3 ± 7.0 to 30.9 ± 5.5 min per session ) , intensity ( 60.4 ± 8.8 to 67.7 ± 6.9 % HR max ) and training impulse ( min × average HR = training impulse/load [ arbitrary units ; AU ] ) ( 2600 ± 1105 to 3210 ± 1269AU ) during the intervention , whilst significantly increasing(P = 0.050 ) their physical composite score ( MSQOL-54 ) at 10 weeks and readiness to exercise ( P = 0.003 ) at 3 months compared with usual care . CONCLUSION This pragmatic intervention was feasible for PwMS , but further research is needed to assess its long-term impact on physical activity behaviour", "Background The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame . Despite an increase in research into the benefits of exercise in people with multiple sclerosis ( PwMS ) , no trial has reported detailed data on effective recruitment strategies for large-scale r and omised controlled trials . The main purpose of this report is to provide a detailed outline of recruitment strategies , rates and estimated costs in the Exercise Intervention for Multiple Sclerosis ( ExIMS ) trial to identify best practice s for future trials involving multiple sclerosis ( MS ) patient recruitment . Methods The ExIMS research ers recruited 120 PwMS to participate in a 12-week exercise intervention . Participants were r and omly allocated to either exercise or usual-care control groups . Participants were sedentary , aged 18–65 years and had Exp and ed Disability Status Scale scores of 1.0–6.5 . Recruitment strategies included attendance at MS outpatient clinics , consultant mail-out and trial awareness-raising activities . Results A total of 120 participants were recruited over the course of 34 months . To achieve this target , 369 potentially eligible and interested participants were identified . A total of 60 % of participants were recruited via MS clinics , 29.2 % from consultant mail-outs and 10.8 % through trial awareness . The r and omisation yields were 33.2 % , 31.0 % and 68.4 % for MS clinic , consultant mail-outs and trial awareness strategies , respectively . The main reason for in eligibility was being too active ( 69.2 % ) , whilst for eligible participants the most common reason for non-participation was the need to travel to the study site ( 15.8 % ) . Recruitment via consultant mail-out was the most cost-effective strategy , with MS clinics being the most time-consuming and most costly . Conclusions To reach recruitment targets in a timely fashion , a variety of methods were employed . Although consultant mail-outs were the most cost-effective recruitment strategy , use of this method alone would not have allowed us to obtain the predetermined number of participants in the required time period , thus leading to costly extensions of the project or failure to reach the number of participants required for sufficient statistical power . Thus , a multifaceted approach to recruitment is recommended for future trials . Trial registration International St and ard R and omised Controlled Trial Registry number : IS RCT N41541516 ; date registered : 5 February 2009", "The Guidelines for Exercise in Multiple Sclerosis ( GEMS ) program is a r and omized controlled trial ( RCT ) examining the feasibility and efficacy of a home-based exercise training program based on recent physical activity guidelines and principles of behavior change for improving symptoms and health-related quality of life ( HRQOL ) in adults with multiple sclerosis ( MS ) . The primary aim is to assess program feasibility in the four domains of process ( e.g. , recruitment , retention , and adherence ) , re sources ( e.g. , communication , staff requirements , and monetary costs ) , management ( e.g. , time and accuracy in data collection /entry , and reporting of adverse events ) and scientific outcomes ( e.g. , safety , burden , participant feedback and efficacy/ outcomes ) . The trial will recruit individuals with mild-to-moderate MS-related disability across the United States who will be r and omized into intervention or waitlist control conditions . All participants will complete home-based assessment s ( including wearing an accelerometer for 7 days and completion of a question naire booklet ) prior to and upon completion of the 4-month program . Participants in the intervention will receive a 4-month home-based exercise program emphasizing aerobic and resistance training . Participants will be provided with exercise equipment , a DVD , a manual and a log-book . The exercise program will be supplemented with periodic newsletters in the mail highlighting principles of behavior change , and video-chats with an exercise specialist to provide motivation and social accountability . This trial serves to inform development of Phase II and III RCTs which can determine the actual efficacy and effectiveness of home-based exercise based on the MS-specific physical activity guidelines for improving symptoms and HRQOL", "We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a r and omised controlled trial . To develop the framework , we undertook a Delphi survey ; ran an open meeting at a trial methodology conference ; conducted a review of definitions outside the health research context ; consulted experts at an international consensus meeting ; and review ed 27 empirical pilot or feasibility studies . We initially adopted mutually exclusive definitions of pilot and feasibility studies . However , some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions . Their viewpoint was supported by definitions outside the health research context , the use of the terms ‘ pilot ’ and ‘ feasibility ’ in the literature , and participants at the international consensus meeting . In our framework , pilot studies are a subset of feasibility studies , rather than the two being mutually exclusive . A feasibility study asks whether something can be done , should we proceed with it , and if so , how . A pilot study asks the same questions but also has a specific design feature : in a pilot study a future study , or part of a future study , is conducted on a smaller scale . We suggest that to facilitate their identification , these studies should be clearly identified using the terms ‘ feasibility ’ or ‘ pilot ’ as appropriate . This should include feasibility studies that are largely qualitative ; we found these difficult to identify in electronic search es because research ers rarely used the term ‘ feasibility ’ in the title or abstract of such studies . Investigators should also report appropriate objectives and methods related to feasibility ; and give clear confirmation that their study is in preparation for a future r and omised controlled trial design ed to assess the effect of an intervention", "Purpose : Participation in physical activity for people with Multiple sclerosis ( MS ) is important but can be difficult to sustain long-term . Facilitators for long-term adherence include choice over activity and control over level of engagement , coupled with support , advice and encouragement from a physiotherapist . This is the basis of Blue Prescription , a novel physiotherapy approach aim ed at optimising long-term adherence with physical activity . We evaluated the feasibility and short-term benefits of Blue Prescription in people with MS . Methods : Twenty-seven people with MS ( mean age : 51 ± 11 years , with a range of MS type and disability ) were assessed at baseline and immediately post-intervention with the MS Impact Scale , MS Self-efficacy Scale , and European Quality of Life Question naire . Change in outcomes were analysed with Wilcoxon signed ranks tests . Results : All participants , irrespective of level of disability , were able to choose a physical activity and to engage in it . The physical component MS Impact Scale score significantly improved by a median change of 6.5 ( 95 % CI = −10.5 to −2.0 ; p = 0.007 ; effect size = 0.38 ) . There were no other significant changes in outcomes . Conclusion : Blue Prescription appears feasible and potentially beneficial , particularly in reducing the negative impacts of MS upon individuals , and thus warrants further evaluation . Implication s for Rehabilitation Facilitators for long-term adherence for disabled people include choice over activity and control over level of engagement , coupled with support , advice and encouragement from a physiotherapist . Blue Prescription is a physiotherapy approach aim ed at optimising long-term adherence with physical activity for people with multiple sclerosis . Blue Prescription appears to reduce the negative impacts of multiple sclerosis upon individuals", "BACKGROUND AND PURPOSE Balance and mobility impairments are common in persons with multiple sclerosis ( MS ) . The primary purpose of this pilot program was to evaluate the feasibility and the effects of group kickboxing on balance and mobility in individuals with MS . METHODS Four individuals with relapsing-remitting or secondary progressive MS participated in a group kickboxing program two times per week for 8 weeks . Outcome measures included the Berg Balance Scale ( BBS ) , Dynamic Gait Index ( DGI ) , Timed Up and Go ( TUG ) , walking speed and the Activities Specific Balance Confidence Scale ( ABC ) . RESULTS Following training , 3 of 4 participants had improvements in BBS performance . All participants demonstrated improvements in the DGI . Changes in the TUG , ABC , and walking speed were more variable . CONCLUSION Group kickboxing appears to be a feasible exercise activity for individuals with MS and may lead to improvement in select measures of balance . Further investigation may be warranted", "The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the principles might also apply . The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct . We followed recommended good practice to develop the extension , including carrying out a Delphi survey , holding a consensus meeting and research team meetings , and piloting the checklist . The aims and objectives of pilot and feasibility r and omised studies differ from those of other r and omised trials . Consequently , although much of the information to be reported in these trials is similar to those in r and omised controlled trials ( RCTs ) assessing effectiveness and efficacy , there are some key differences in the type of information and in the appropriate interpretation of st and ard CONSORT reporting items . We have retained some of the original CONSORT statement items , but most have been adapted , some removed , and new items added . The new items cover how participants were identified and consent obtained ; if applicable , the prespecified criteria used to judge whether or how to proceed with a future definitive RCT ; if relevant , other important unintended consequences ; implication s for progression from pilot to future definitive RCT , including any proposed amendments ; and ethical approval or approval by a research review committee confirmed with a reference number . This article includes the 26 item checklist , a separate checklist for the abstract , a template for a CONSORT flowchart for these studies , and an explanation of the changes made and supporting examples . We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials . Editor ’s note : In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites", "The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the principles might also apply . The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct . We followed recommended good practice to develop the extension , including carrying out a Delphi survey , holding a consensus meeting and research team meetings , and piloting the checklist . The aims and objectives of pilot and feasibility r and omised studies differ from those of other r and omised trials . Consequently , although much of the information to be reported in these trials is similar to those in r and omised controlled trials ( RCTs ) assessing effectiveness and efficacy , there are some key differences in the type of information and in the appropriate interpretation of st and ard CONSORT reporting items . We have retained some of the original CONSORT statement items , but most have been adapted , some removed , and new items added . The new items cover how participants were identified and consent obtained ; if applicable , the prespecified criteria used to judge whether or how to proceed with a future definitive RCT ; if relevant , other important unintended consequences ; implication s for progression from pilot to future definitive RCT , including any proposed amendments ; and ethical approval or approval by a research review committee confirmed with a reference number . This article includes the 26 item checklist , a separate checklist for the abstract , a template for a CONSORT flowchart for these studies , and an explanation of the changes made and supporting examples . We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials . Editor ’s note : In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites", "Pilot studies play an important role in health research , but they can be misused , mistreated and misrepresented . In this paper we focus on pilot studies that are used specifically to plan a r and omized controlled trial ( RCT ) . Citing examples from the literature , we provide a method ological framework in which to work , and discuss reasons why a pilot study might be undertaken . A well-conducted pilot study , giving a clear list of aims and objectives within a formal framework will encourage method ological rigour , ensure that the work is scientifically valid and publishable , and will lead to higher quality RCTs . It will also safeguard against pilot studies being conducted simply because of small numbers of available patients", "Background The aim of this study was to evaluate the safety , feasibility and preliminary effects of a high-intensity rehabilitative task-oriented circuit training ( TOCT ) in a sample of multiple sclerosis ( MS ) subjects on walking competency , mobility , fatigue and health-related quality of life ( HRQoL ) . Methods 24 MS subjects ( EDSS 4.89 ± 0.54 , 17 female and 7 male , 52.58 ± 11.21 years , MS duration 15.21 ± 8.68 years ) have been enrolled and r and omly assigned to 2 treatment groups : ( i ) experimental group received 10 TOCT sessions over 2 weeks ( 2 hours/each session ) followed by a 3 months home exercise program , whereas control group did not receive any specific rehabilitation intervention . A feasibility patient-reported question naire was administered after TOCT . Functional outcome measures were : walking endurance ( Six Minute Walk Test ) , gait speed ( 10 Meter Walk Test ) , mobility ( Timed Up and Go test ) and balance ( Dynamic Gait Index ) . Furthermore , self-reported question naire of motor fatigue ( Fatigue Severity Scale ) , walking ability ( Multiple Sclerosis Walking Scale – 12 ) and health-related quality of life ( Multiple Sclerosis Impact Scale – 29 ) were included . Subjects ’ assessment s were delivered at baseline ( T0 ) , after TOCT ( T1 ) and 3 months of home-based exercise program ( T2 ) . Results After TOCT subjects reported a positive global rating on the received treatment . At 3 months , we found a 58.33 % of adherence to the home-exercise program . After TOCT , walking ability and health-related quality of life were improved ( p high-intensity task-oriented circuit class training followed by a three months home-based exercise program seems feasible and safe in MS people with moderate mobility impairments ; moreover it might improve walking abilities . Trial registration", "Objective : To determine if exercise benefits patients with multiple sclerosis . Design : R and omized controlled trial . Setting s : Participants exercised at home and also attended exercise classes held in a hospital physiotherapy gym . Subjects : Thirty patients , diagnosed and independently mobile , were recruited in the Dublin area . Intervention : For three months , classes were held twice-weekly and participants exercised independently once-weekly . The control group was monitored monthly and management remained unchanged . Measurements : Measurements were taken at baseline , three and six months . The Modified Fatigue Impact Scale ( MFIS ) , Multiple Sclerosis Impact Scale-29 ( MSIS-29 ) and Functional Assessment of Multiple Sclerosis ( FAMS ) were used to measure fatigue and quality of life ( QOL ) . Heart rate ( HR ) and the Borg 's Rating of Perceived Exertion ( RPE ) were recorded during an incremental exercise test . The change from baseline scores between groups was compared using the Mann — Whitney U-test . Results : Twenty-four participants completed the programme ( n = 12 in each group ) . Based on the change in scores at three months , the exercise group had significantly greater improvements in exercise capacity ( HR : —14 [ -18.5 , -2.5 ] versus 0.5 [ -4 , 5.5 ] , P= 0.009 ) , QOL ( FAMS : 23 [ 9.5 , 42.5 ] versus -3.5 [ -16 , 5 ] , P=0.006 ) and fatigue ( MFIS : -13 [ -20 , -3 ] versus 1 [ -4 , 4.5 ] , P=0.02 ) . At six months , the difference in change scores remained significant for FAMS ( 19 [ 14 , 31 ] versus -4.5 [ -25 , 8 ] , P=0.002 ) and MFIS ( -8.5 [ -19.5 , -1 ] versus 0.5 [ -2.5 , 6.5 ] , P=0.02 ) only . Conclusions : A three-month exercise programme improved participants ' exercise capacity , QOL and fatigue , with the improvements in QOL and fatigue lasting beyond the programme", "Background : Exercise is a safe , non-pharmacological adjunctive treatment for people with multiple sclerosis but cost-effective approaches to implementing exercise within health care setting s are needed . Objective : The objective of this paper is to assess the cost effectiveness of a pragmatic exercise intervention in conjunction with usual care compared to usual care only in people with mild to moderate multiple sclerosis . Methods : A cost-utility analysis of a pragmatic r and omised controlled trial over nine months of follow-up was conducted . A total of 120 people with multiple sclerosis were r and omised ( 1:1 ) to the intervention or usual care . Exercising participants received 18 supervised and 18 home exercise sessions over 12 weeks . The primary outcome for the cost utility analysis was the incremental cost per quality -adjusted life year ( QALY ) gained , calculated using utilities measured by the EQ-5D question naire . Results : The incremental cost per QALY of the intervention was £ 10,137 per QALY gained compared to usual care . The probability of being cost effective at a £ 20,000 per QALY threshold was 0.75 , rising to 0.78 at a £ 30,000 per QALY threshold . Conclusion : The pragmatic exercise intervention is highly likely to be cost effective at current established thresholds , and there is scope for it to be tailored to particular sub-groups of patients or services to reduce its cost impact", "Background : While there is an increasing body of evidence supporting the efficacy of exercise in people with multiple sclerosis ( MS ) , additional information on the effectiveness of combining aerobic and resistance training , and yoga is required . Objectives : This study evaluated the effectiveness of community exercise interventions for people with MS having minimal gait impairment . Methods : A multi-centred , block-r and omised , assessor-blinded , controlled trial was conducted . Participants were r and omised in groups of eight to physiotherapist (PT)-led exercise ( n = 80 ) , yoga ( n = 77 ) , fitness instructor (FI)-led exercise ( n = 86 ) and they took part in weekly community-based group exercise sessions . Those in the control group were asked not to change of their exercise habits ( n = 71 ) . The primary outcome was the Multiple Sclerosis Impact Scale ( MSIS ) 29v2 physical component , measured before and after the 10-week intervention . Secondary outcomes were the MSIS 29v2 psychological component , the Modified Fatigue Impact Scale ( MFIS ) and the 6-Minute Walk Test ( 6MWT ) . Results : The group x time interaction approached significance for the MSIS-29v2 physical component ( f = 2.48 , p = 0.061 ) and MFIS total ( f = 2.50 , p = 0.06 ) , and it was significant for the MFIS physical subscale ( f = 4.23 , p = 0.006 ) . All three exercise interventions led to a statistically significant improvement on the MSIS-29 psychological component and both the MFIS total and physical subscales , which were greater than the control ( p the PT-led and FI-led interventions significantly improved the MSIS-29 physical and 6MWT to levels greater than the control ( p < 0.05 ) . Conclusions : This study provides evidence for the positive effect of exercise on the physical impact of MS and fatigue . The group nature of the classes may have contributed to the positive effects seen on the psychological impact of MS", "Background and Purpose Physical deconditioning is involved in the impaired exercise tolerance of patients with multiple sclerosis ( MS ) , but data on the effects of aerobic training ( AT ) in this population are scanty . The purpose of this study was to compare the effects of an 8-week AT program on exercise capacity — in terms of walking capacity and maximum exercise tolerance , as well as its effects on fatigue and health-related quality of life — as compared with neurological rehabilitation ( NR ) in subjects with MS . Subjects and Methods Nineteen subjects ( 14 female , 5 male ; mean age [X̄±SD]=41±8 years ) with mild to moderate disability secondary to MS participated in a r and omized crossover controlled study . Eleven subjects ( 8 female , 3 male ; mean age [X̄±SD]=44±6 years ) completed the study . Results After AT , but not NR , the subjects ’ walking distances and speeds during a self-paced walk were significantly improved , as were their maximum work rate , peak oxygen uptake , and oxygen pulse during cardiopulmonary exercise tests . The increases in peak oxygen uptake and maximum work rate , but not in walking capacity , were significantly higher after AT , as compared with after NR . Additionally , the subjects who were most disabled tended to benefit more from AT . There were no differences between AT and NR in effects on fatigue , and the results showed that AT may have partially affected health-related quality of life . Discussion and Conclusion The results suggest that AT is more effective than NR in improving maximum exercise tolerance and walking capacity in people with mild to moderate disability secondary to MS", "Objective : To determine the feasibility of three fall prevention programs delivered over 12 weeks among individuals with multiple sclerosis : ( A ) a home-based exercise program targeting physiological risk factors ; ( B ) an educational program targeting behavioral risk factors ; and ( C ) a combined exercise- and -education program targeting both factors . Design : R and omized controlled trial . Setting : Home-based training with assessment s at research laboratory . Participants : A total of 103 individuals inquired about the investigation . After screening , 37 individuals with multiple sclerosis who had fallen in the last year and ranged in age from 45–75 years volunteered for the investigation . A total of 34 participants completed post assessment following the 12-week intervention . Intervention : Participants were r and omly assigned into one of four conditions : ( 1 ) wait-list control ( n = 9 ) ; ( 2 ) home-based exercise ( n = 11 ) ; ( 3 ) education ( n = 9 ) ; or ( 4 ) a combined exercise and education ( n = 8) group . Measures : Before and after the 12-week interventions , participants underwent a fall risk assessment as determined by the physiological profile assessment and provided information on their fall prevention behaviors as indexed by the Falls Prevention Strategy Survey . Participants completed falls diaries during the three-months postintervention . Results : A total of 34 participants completed postintervention testing . Procedures and processes were found to be feasible . Overall , fall risk scores were lower in the exercise groups ( 1.15 SD 1.31 ) compared with the non-exercise groups ( 2.04 SD 1.04 ) following the intervention ( p in fall prevention behaviors ( p > 0.05 ) . Conclusions : Further examination of home-based exercise/education programs for reducing falls in individuals with multiple sclerosis is warranted . A total of 108 participants would be needed in a larger r and omized controlled trial . Clinical Trials.org #", "Abstract Purpose : To test the feasibility and acceptability of an implementation intention strategy ( if-then plans ) increasingly used in health psychology to bridge the goal intention – action gap in rehabilitation with people with neurological conditions who are experiencing difficulties with mobility . Methods : Twenty people with multiple sclerosis ( MS ) and stroke , r and omised to an experimental and control group , set up to three mobility related goals with a physiotherapist . The experimental group also formulated if-then plans for every goal . Data collection : Focus groups and interviews with participants and therapists ; Patient Activation Measure ( PAM ) , 10-m walk test , Rivermead Mobility Index , self-efficacy , subjective health status , quality of life . Results : Qualitative data highlighted one main theme : Rehabilitation in context , encapsulating the usefulness of the if-then strategy in thinking about the patient in the context of complexity , the usefulness of home-based rehabilitation , and the perceived need for a few more sessions . Changes in walking speed were in the expected direction for both groups ; PAM scores improved over 3 months in both groups . Conclusion : If-then plans were feasible and acceptable in bridging the goal intention – action gap in rehabilitation with people with MS and stroke , who are experiencing difficulties with mobility . This approach can now be adapted and trialled further in a definitive study . Implication s for Rehabilitation Goal planning in rehabilitation necessitates specific strategies that help people engage in goal -related tasks . If-then plans aim to support people to deal more effectively with self-regulatory problems that might undermine goal striving and have been found to be effective in health promotion and health behaviour change . This feasibility study with people with a stroke and multiple sclerosis has demonstrated that if-then plans are feasible and acceptable to patients and physiotherapists in supporting goal -directed behaviour", "OBJECTIVE To investigate the feasibility and preliminary outcomes of a home progressive resistance training ( PRT ) program augmented by neuromuscular electrical stimulation ( NMES ) . DESIGN R and omized controlled pilot trial . SETTING Participant homes . PARTICIPANTS People with multiple sclerosis ( MS ) ( N=37 ) who use a walking aid . INTERVENTIONS A 12-week home PRT program or the same program augmented by NMES . MAIN OUTCOME MEASURES Strength using h and -held dynamometry ; repeated sit to st and test ; Berg Balance Scale ; timed Up & Go test ; 12-Item Multiple Sclerosis Walking Scale ; Multiple Sclerosis Impact Scale-29 , version 2 ; and Modified Fatigue Impact Scale ( MFIS ) . The NMES group also completed a device usability question naire . RESULTS Only change in MFIS score was significantly greater in the NMES group than the PRT group ( P=.012 ) . The NMES group improved significantly in quadriceps endurance ( median of change , 8.5 ; P=.043 ) , balance ( median of change , 3.5 ; P=.001 ) , physical impact of MS ( median of change , -8.3 ; P=.001 ) , and impact of fatigue ( median of change , -17 ; P=.001 ) . Participants rated the device as highly usable . CONCLUSIONS This pilot study suggests that a home PRT program with NMES is feasible , and the neuromuscular electrical stimulation device is usable by this population . Only reduction in impact of fatigue was greater in the NMES than the PRT group", "Background : The most effective exercise dose has yet to be established for multiple sclerosis ( MS ) . Objective : The aim of this study was to investigate the effect of different exercise intensities in people with MS . Methods : We completed a r and omized comparator study of three cycling exercise intensities , with blinded assessment , was carried out in Oxford . Sixty-one adults with MS who fulfilled inclusion criteria were r and omized at entry into the study , using a computer-generated list held by an exercise professional , into either : continuous ( at 45 % peak power , n = 20 ) , intermittent ( 30 sec on , 30 sec off at 90 % peak power , n = 21 ) or combined ( 10 min intermittent at 90 % peak power then 10 min continuous at 45 % peak power , n = 20 ) exercise for 20 min twice a week for 12 weeks in a leisure facility . Groups were assessed at : baseline , halfway ( 6 weeks ) , end intervention ( 12 weeks ) and follow-up ( 24 weeks ) . Primary outcome measure was 2 min walk . Results : Fifty-five participants were included in the analysis ( n = continuous 20 , intermittent 18 , combined 17 ) . No differences were found between groups . After 6 weeks , considering all participants , 2 min walk distance increased by 6.96 ± 2.56 m ( 95 % CI : 1.81 to 12.10 , effect size ( es ) : 0.25 , p es : 0.04 ) . Two minute walk did not significantly change between further assessment s. Between 6 and 12 weeks there was a drop in attendance that seemed to be associated with the intermittent and combined groups ; these groups also had a greater number of adverse events ( leg pain during cycling most common ) and dropouts ( n = continuous 1 , intermittent 5 , combined 10 ) . Considering all participants , 6 weeks of cycling exercise produced benefits in mobility that were maintained with further sessions . Conclusion : While no differences were found between groups , greater benefit may be associated with higher-intensity exercise , but this may be less well tolerated . CONSORT - trial registration number ( IS RCT N89009719", "Background : Few high- quality trials have examined the effects of progressive resistance training ( PRT ) on people with multiple sclerosis ( MS ) . Objective : To determine the effectiveness of PRT for people with MS , focusing on improving the gait deficits common in this population . Methods : Using a single blind r and omized controlled trial , people with relapsing – remitting MS were r and omly allocated to either a PRT program targeting the lower limb muscles twice a week for 10 weeks ( n = 36 ) , or usual care plus an attention and social program conducted once a week for 10 weeks ( n = 35 ) . Outcomes were recorded at baseline , week 10 and week 22 . Results : Participants attended 92 % of training sessions , with no serious adverse events . At 10 weeks , no differences were detected in walking performance . However , compared with the comparison group PRT demonstrated increased leg press strength ( 16.8 % , SD 4.5 ) , increased reverse leg press strength ( 29.8 % , SD 12.7 ) , and increased muscle endurance of the reverse leg press ( 38.7 % , SD 32.8 ) . Improvements in favor of PRT were also found for physical fatigue ( Mean difference −3.9 units , 95%CI −6.6 to −1.3 ) , and the physical health domain of quality of life ( Mean difference 1.5 units , 95%CI 0.1 to 2.9 ) . At week 22 almost no between-group differences remained . Conclusion : PRT is a relatively safe intervention that can have short-term effects on reducing physical fatigue , increasing muscle endurance and can lead to small improvements in muscle strength and quality of life in people with relapsing – remitting MS . However , no improvements in walking performance were observed and benefits do not appear to persist if training is completely stopped", "Objective : Investigate the feasibility and potential efficacy of a customized print-based intervention to promote physical activity and symptom self-management in women with multiple sclerosis . Design : A r and omly allocated two-group repeated measures design , with a delayed-treatment contact group serving as the control . Participants were r and omized to receive the intervention immediately ( n = 14 ) or receive it at week 12 ( n = 16 ) . Outcome measures were administered at weeks 1 , 12 , and 24 . Setting : Community-based in metropolitan area . Subjects : Thirty women with multiple sclerosis . Intervention : Prescribing a home-exercise program and following up with customized pamphlets , which are matched to participants ’ stage of readiness to change physical activity behavior and physical activity barriers ( e.g. encouraging self-management of symptoms ) . Main Measures : Physical Activity and Disability Survey-revised , Godin Leisure-Time Exercise Question naire , SF-12 , Symptoms of Multiple Sclerosis Scale , and 6-minute walk test . Results : Intent-to-treat analyses using mixed multivariate analysis of variance ( MANOVA ) were conducted on ( 1 ) physical activity levels and ( 2 ) health and function outcomes . The mixed MANOVAs for physical activity levels and health and function outcomes indicated significant improvements in the immediate group compared with the delayed group ( i.e. condition by time interaction was significant , Wilks ’ λ = 0.59 , F2 , 27 = 9.31 , P = 0.001 and Wilks ’ λ = 0.70 , F4 , 25 = 2.72 , P = 0.052 , respectively ) . The intervention had moderate to large effect sizes in improving physical activity levels ( d = 0.63 to 0.89 ) , perceptions of physical function ( d = 0.63 ) , and 6-minute walk test ( d=0.86 ) . Conclusion : This pilot study indicates that a customized print-based intervention shows promise in improving physical activity levels and health and function in women with multiple sclerosis", "This pilot study investigated whether 4 weeks of aerobic treadmill training in individuals with multiple sclerosis ( MS ) improved mobility and reduced fatigue . Individuals with MS were recruited to this prospect i ve , r and omised controlled trial . Individuals were assessed at baseline , week 7 and 12 with a 10 metre timed walk , a 2 minute walk , the Rivermead Mobility Index , and the Fatigue Severity Scale . After a pre- assessment familiarisation session and a baseline assessment , individuals were r and omly allocated to an initial intervention or delayed intervention group . Treadmill training consisted of 4 weeks of supervised aerobic exercise delivered weeks 3–6 in the immediate group and 8–11 in the delayed group . Of the initial 19 recruits , 16 individuals completed the study . There was a significant difference in walking endurance between the delayed and immediate groups at baseline ( p decreases in 10 metre walk time were found in both groups , which was significant in the immediate group ( p The 2 minute walk distance significantly increased in both groups ( p changes in fatigue scores were found . This study showed that in individuals with MS , aerobic treadmill training is feasible and well tolerated . Walking speed and endurance increased following training with no increase in reported fatigue . Detraining occurred in the period following training . A larger r and omised clinical trial is warranted", "People with multiple sclerosis ( MS ) are likely to benefit from regular exercise , but physical inactivity is more common among people with MS than among the general population . This small r and omized study evaluated whether motivational interviewing ( MI ) affects adherence to and personal experience in an exercise program . Inactive people with MS participating in an eight-week exercise program were r and omized to either three brief MI ( n = 7 ) or three health coaching ( n = 6 ) sessions . Session attendance for both conditions was high , and MI fidelity was rigorously and reliably measured using the Motivational Interviewing Treatment Integrity Scales . The feasibility of using this approach was demonstrated with a small sample . Large effects favoring the MI condition were found for physical exertion , affect during exercise , and fatigue , but no effects were found for adherence to the exercise program . Treatment integrity measures of MI were correlated with outcomes in expected directions . Although this study demonstrated the feasibility of this MI approach , the large effect sizes found should be viewed with substantial skepticism and replicated in sufficiently powered studies using objective measures of exercise adherence", "There is increasing recognition that exercise is an efficacious strategy for managing many consequences of multiple sclerosis ( MS ) , yet persons with MS are not engaging in sufficient exercise for accruing health benefits . Poor exercise uptake might be associated with the design of previous research . We conducted a r and omised controlled trial ( RCT ) for examining the feasibility of a 4-month home-based , exercise-training program design ed based on recent physical activity guidelines for MS and supplemented by behavioural strategies for compliance . Feasibility was assessed in the domains of process ( e.g. , recruitment ) , re source ( e.g. , monetary costs ) , management ( e.g. , personnel time requirements ) and scientific outcomes ( e.g. , treatment effect ) . We recruited persons with mild-to-moderate MS who were r and omised into an intervention or wait-list control condition . Intervention participants received a pedometer , elastic resistance b and s , DVD , training manual , calendars , log-book , video coaching calls and newsletters . Participants in both conditions completed home-based assessment s before and after the 4-month period . Ninety-nine persons with MS were assessed for eligibility , and 57 were r and omised . Fifty-one persons completed the study ( 90 % ) . Total costs of the study were US $ 5331.03 . Personnel time to conduct the study totaled 263h . Participants in the intervention group complied fully with 71 % of all exercise sessions . There was a moderate increase in self-reported exercise behaviour of the intervention participants as measured by the Godin Leisure-Time Exercise Question naire ( d≥0.5 ) . The results support the feasibility and acceptability of a home-based exercise intervention based on physical activity guidelines and supplemented with behavioural strategies for adults with mild-to-moderate MS", "Abstract Purpose : This mixed methods study aim ed to explore the feasibility , efficacy and the participants ’ experiences of a Pilates programme for people with Multiple Sclerosis ( pwMS ) who use a wheelchair . Method : Fifteen pwMS took part in the 12-week Pilates programme . At baseline and after 6 and 12 weeks of the programme , sitting stability , measured as maximum progression of the Centre of Pressure when leaning sideways ( COPmax ) , posture , pain on a Visual Analogue Scale , function , fatigue and the impact of MS ( MSIS29 ) were assessed . Ten participants took part in two focus groups within six weeks of the completion of the programme . Results : Significant improvements at the 12-week assessment were found in COPmax ( p = 0.046 ) , sitting posture ( p = 0.004 ) , pain in the shoulders ( p = 0.005 ) and back ( p = 0.005 ) and MSIS29 ( p = 0.006 ) . The majority of participants described various physical , functional , psychological and social benefits from participation that reflected increased confidence in activities of daily living . Enjoyment of the classes was expressed by all , and most wished to continue participation . Conclusions : Pilates appears to be efficacious in improving sitting stability and posture and decreasing pain and was also well tolerated by wheelchair users with MS . Further mixed methods studies are warranted . Implication s for Rehabilitation Group-based core stability exercise or Pilates for people with MS who use wheelchair is a feasible and safe way of exercising for this patient group . Pilates exercises for people moderately to severely affected by MS result ed in a decrease in back and shoulder pain and improvement in sitting balance . Future appropriately powered r and omised controlled studies into Pilates for people with MS reliant on wheelchair are warranted" ]

[ "The aim of this case series was to investigate changes in pain and pressure pain sensitivity after manual treatment of active trigger points ( TrPs ) in the shoulder muscles in individuals with unilateral shoulder impingement . Twelve patients ( 7 men , 5 women , age : 25 ± 9 years ) diagnosed with unilateral shoulder impingement attended 4 sessions for 2 weeks ( 2 sessions/week ) . They received TrP pressure release and neuromuscular interventions over each active TrP that was found . The outcome measures were pain during arm elevation ( visual analogue scale , VAS ) and pressure pain thresholds ( PPT ) over levator scapulae , supraspinatus infraspinatus , pectoralis major , and tibialis anterior muscles . Pain was captured pre-intervention and at a 1-month follow-up , whereas PPT were assessed pre- and post-treatment , and at a 1-month follow-up . Patients experienced a significant ( P reduction in pain after treatment ( mean ± SD : 1.3 ± 0.5 ) with a large effect size ( d > 1 ) . In addition , patients also experienced a significant increase in PPT immediate after the treatment ( P 1).A significant negative association ( r(s ) = -0.525 ; P = 0.049 ) between the increase in PPT over the supraspinatus muscle and the decrease in pain was found : the greater the decrease in pain , the greater the increase in PPT . This case series has shown that manual treatment of active muscle TrPs can help to reduce shoulder pain and pressure sensitivity in shoulder impingement . Current findings suggest that active TrPs in the shoulder musculature may contribute directly to shoulder complaint and sensitization in patients with shoulder impingement syndrome , although future r and omized controlled trials are required", "Objectives : To investigate the test-retest reliability of the following clinical diagnostic characteristics of myofascial trigger points : taut b and , spot tenderness , jump sign , pain recognition , referred pain and local twitch responses ( LTRs ) . Design : Test-retest reliability study . Setting : This study was undertaken in an outpatient physiotherapy department . Subjects : Fifty-eight patients ( 31 males and 27 females ) with rotator cuff tendonitis were recruited into this study . Intervention : Rotator cuff muscles were assessed by an expert for the presence or absence of the main clinical diagnostic characteristics of trigger point assessment . The process was then repeated three days later by the same expert . Main measures : Outcomes included the presence or absence of : a taut b and , spot tenderness , jump sign , pain recognition , referred pain and LTRs . Results : Kappa values between testing situations for the taut b and , spot tenderness , jump sign and pain recognition were 1 . Kappa scores for referred pain ranged between 0.79 and 0.88 and for the local twitch response between 0.75 and 1 depending on the muscles under investigation . Conclusions : The presence or absence of the taut b and , spot tenderness , jump sign and pain recognition was highly reliable between sessions . Referred pain and local twitch response reliability varied depending on the muscle being studied", "BACKGROUND Myofascial trigger points ( MTrPs ) are commonly observed in the neck , parascapular region , and upper back muscles of patients with cervical pathology . AIM To assess the frequency of latent and active myofascial trigger point ( aMTrP ) in the neck and upper back muscles in patients with cervical radiculopathy and healthy subjects . DESIGN Controlled clinical trials . SETTING Out patients and controls . POPULATION Two hundred and forty four patients and 122 controls METHODS The patients clinical ly diagnosed as cervical radiculopathy with positive Spurling 's test and confirmed by MRI , were enrolled in this study . All subjects were examined for active and latent MTrP. In patients with cervical radiculopathy , an aMTrP was distinguished from a latent one when the referred pain elicited by exploration of the MTrP is recognized as familiar . RESULTS The patients comprised of 128 female ( 52.5 % ) and 116 male ( 47.5 % ) patients . Mean age was 44.58(20 - 65 years ) . In 125 ( 51.2 % ) of patients with cervical radiculopathy were found an aMTrP at least one muscle from upper trapezius , multifidus , splenius capitis , levator scapulae , rhomboid major , minor and deep paraspinal muscles . Number and distribution of MTrPs in patients with 244 cervical radiculopathy and in healthy controls . aMTrPs were detected most common in levator scapula ( 16.3 % ) , splenius capitis ( 14.7 % ) , rhomboid minor ( 14.3 % ) , upper part of trapezius ( 13.5 % ) , rhomboid major ( 10.2 % ) and multifidus ( 8.6 % ) muscles . Patients with cervical radiculopathy showed latent MTrP in levator scapula ( 27 % ) , splenius capitis ( 16.8 % ) , rhomboid minor ( 24.6 % ) , upper part of trapezius ( 33.2 % ) , rhomboid major ( 9 % ) and multifidus ( 8.2 % ) muscles . There was significant difference in terms of distribution of active and latent MTrPs in patients with cervical radiculopathy ( P=0.019 ) . Number of latent MTrPs in upper trapezius muscles in patients with cervical radiculopathy was more than the expected distribution . None of the subjects of control group had aMTrP. However , healthy controls showed latent MTrP in levator scapula ( 33.6 % ) , splenius capitis ( 16.4 % ) , rhomboid minor ( 21.3 % ) , upper part of trapezius ( 40.2 % ) , rhomboid major ( 6.5 % ) and multifidus ( 17.2 % ) muscles . There was no significant difference in terms of distribution of latent MTrPs between cervical radiculopathy and control groups ( P=0.249 ) . The frequency of aMTrP was found to be significantly higher in CDH with median localization as compared to posterolateral herniations ( P=0.041 ) . After conservative treatment for two weeks , number of patients with active MTrP in cervical radiculopathy were decreased about 50 % . CONCLUSION Cervical root compression would be considered as the starting or maintaining factor of aMTrP. CLINICAL REHABILITATION IMPACT The treatment of cervical radiculopathy might be facilitated the improving in aMTrPs located in aforementioned muscles", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "OBJECTIVE The purpose of this study was to evaluate the effects of including 1 session of trigger point dry needling ( TrP-DN ) into a multimodal physiotherapy treatment on pain and function in postoperative shoulder pain . METHODS Twenty patients ( 5 male ; 15 female ; age , 58 ± 12 years ) with postoperative shoulder pain after either open reduction and internal fixation with Proximal Humeral Internal Locking System plate plate or rotator cuff tear repair were r and omly divided into 2 groups : physiotherapy group ( n = 10 ) who received best evidence physical therapy interventions and a physical therapy plus TrP-DN group ( n = 10 ) who received the same intervention plus a single session of TrP-DN targeted at active TrPs . The Constant-Murley score was used to determine pain , activities of daily living , range of motion , and strength , which was captured at baseline and 1 week after by an assessor blinded to group assignment . RESULTS Analysis of variance showed that subjects receiving TrP-DN plus physical therapy exhibited greater improvement in the Constant-Murley total score ( P also activities of daily living ( P and strength ( P = .019 ) subscales than those receiving physical therapy alone . Between-group effect sizes were large in favor of the TrP-DN group ( 0.97 similar improvements in pain ( P and range of motion ( P of TrP-DN in the first week of a multimodal physical therapy approach may assist with faster increases in function in individuals with postoperative shoulder pain", "OBJECTIVES To evaluate the association between episodic migraines and the prevalence of myofascial trigger points ( MTrPs ) in the sternocleidomastoid and upper trapezius , forward head posture ( FHP ) , neck range of motion ( ROM ) and cervical facet joint stiffness . METHODS 20 physiotherapy students with episodic migraines and 20 age- and sex matched healthy controls were included in this observational case-control study . Demographics and headache status were evaluated through question naires . Active neck ROM , presence of MTrPs , and cervical facet joint mobility were assessed by physical examination . FHP was measured using a lateral digital photograph taken in a sitting position . RESULTS No significant differences were found in neck ROM measurements and FHP between the migraine and control groups . Significant differences were found in the prevalence of cervical facet joints stiffness in Occiput-C1 ( χ(2 ) = 4.444 , p = 0.035 ) and C1-C2 ( χ(2 ) = 10.157 , p = 0.001 ) , but not in other segments . Significant differences were found in the prevalence of active and latent MTrPs between the migraine and control subjects in the right trapezius ( χ(2 ) = 11.649 , p = 0.003 ) and right sternocleidomastoid ( χ(2 ) = 8.485 , p = 0.014 ) . CONCLUSIONS Our findings support the hypothesis that the prevalence of MTrPs in neck muscles and hypomobility in the upper cervical facet joints are associated with migraines ", "Background Shoulder pain is reported to be highly prevalent and tends to be recurrent or persistent despite medical treatment . The pathophysiological mechanisms of shoulder pain are poorly understood . Furthermore , there is little evidence supporting the effectiveness of current treatment protocol s. Although myofascial trigger points ( MTrPs ) are rarely mentioned in relation to shoulder pain , they may present an alternative underlying mechanism , which would provide new treatment targets through MTrP inactivation . While previous research has demonstrated that trained physiotherapists can reliably identify MTrPs in patients with shoulder pain , the percentage of patients who actually have MTrPs remains unclear . The aim of this observational study was to assess the prevalence of muscles with MTrPs and the association between MTrPs and the severity of pain and functioning in patients with chronic non-traumatic unilateral shoulder pain . Methods An observational study was conducted . Subjects were recruited from patients participating in a controlled trial study ing the effectiveness of physical therapy on patients with unilateral non-traumatic shoulder pain . Sociodemographic and patient-reported symptom scores , including the Disabilities of the Arm , Shoulder , and H and ( DASH ) Question naire , and Visual Analogue Scales for Pain were compared with other studies . To test for differences in age , gender distribution , and education level between the current study population and the population s from Dutch shoulder studies , the one sample T-test was used . One observer examined all subjects ( n = 72 ) for the presence of MTrPs . Frequency distributions , means , medians , st and ard deviations , and 95 % confidence intervals were calculated for descriptive purpose s. The Spearman 's rank-order correlation ( ρ ) was used to test for association between variables . Results MTrPs were identified in all subjects . The median number of muscles with MTrPs per subject was 6 ( active MTrPs ) and 4 ( latent MTrPs ) . Active MTrPs were most prevalent in the infraspinatus ( 77 % ) and the upper trapezius muscles ( 58 % ) , whereas latent MTrPs were most prevalent in the teres major ( 49 % ) and anterior deltoid muscles ( 38 % ) . The number of muscles with active MTrPs was only moderately correlated with the DASH score . Conclusion The prevalence of muscles containing active and latent MTrPs in a sample of patients with chronic non-traumatic shoulder pain was high" ]

[ "Background High-amylose maize resistant starch type 2 ( HAM-RS2 ) stimulates gut-derived satiety peptides and reduces adiposity in animals . Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk . The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight , healthy adults . We also examined changes in biomarkers of satiety ( glucagon-like peptide-1 [ GLP-1 ] , peptide YY [ PYY ] , and leptin ) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry , dietary intake , and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption . Methods Using a r and omized-controlled , parallel-arm , double-blind design , 18 overweight , healthy adults consumed either muffins enriched with 30 g HAM-RS2 ( n = 11 ) or 0 g HAM-RS2 ( control ; n = 7 ) daily for 6 weeks . The HAM-RS2 and control muffins were similar in total calories and available carbohydrate . Results At baseline , total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group ( P = 0.043 ) . Within the HAM-RS2 group , the area under the curve ( AUC ) glucose ( P = 0.028 ) , AUC leptin ( P = 0.022 ) , and postpr and ial 120-min leptin ( P = 0.028 ) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks . Fasting total PYY increased ( P = 0.033 ) in the HAM-RS2 group , but changes in insulin or total GLP-1 were not observed . Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake . The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet ( mean range 34.5 % to 39.4 % of total calories ) . Conclusion Consuming 30 g HAM-RS2 daily for 6 weeks can improve glucose homeostasis , lower leptin concentrations , and increase fasting PYY in healthy overweight adults without impacting body composition and may aid in the prevention of chronic disease . However , between-group differences in biomarkers were not observed and future research is warranted before specific recommendations can be made . Trial registration None", "OBJECTIVE To observe the effects of resistant starch ( RS ) on insulin resistance ( IR ) in type 2 diabetes mellitus patients . METHODS All 40 patients with type 2 diabetes mellitus were r and omly divided into two groups : Group A and Group B. Cross- design of two stages ( I , II ) was used during observation . Group A received RS 30 g/d as an intervention group for ahead of 4 weeks ( I stage ) , while group B as a control group . Group B was given RS in late 4 weeks ( II stage ) , while Group A as served control group . Blood was taken the first day and on the latest day in each stage . Fasting blood glucose ( FBG ) , post blood glucose ( PBG ) , fructosamine ( FMN ) , total cholesterol ( TC ) , triglyceridemic ( TG ) , insulin sensitive index ( ISI ) , and body mass index ( BMI ) were measured , respectively . RESULTS As Compared with the control group , ISI was higher and FBG , PBG , TC , TG , FMN and BMI were significantly lower in intervention group ( P RS should be effective in improving IR of type 2 diabetes mellitus patients", "Resistant starch ( RS ) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome , but its effects on human type 2 diabetes ( T2DM ) are unknown . This study aim ed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postpr and ial metabolites and body fat in T2DM . Seventeen individuals with well-controlled T2DM ( HbA1c 46.6±2 mmol/mol ) consumed , in a r and om order , either 40 g of type 2 RS ( HAM-RS2 ) or a placebo , daily for 12 weeks with a 12-week washout period in between . At the end of each intervention period , participants attended for three metabolic investigations : a two-step euglycemic – hyperinsulinemic clamp combined with an infusion of [ 6,6 - 2H2 ] glucose , a meal tolerance test ( MTT ) with arterio-venous sampling across the forearm , and whole-body imaging . HAM-RS2 result ed in significantly lower postpr and ial glucose concentrations ( P=0.045 ) and a trend for greater glucose uptake across the forearm muscle ( P=0.077 ) ; however , there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity , or on HbA1c . Fasting non-esterified fatty acid ( NEFA ) concentrations were significantly lower ( P=0.004 ) and NEFA suppression was greater during the clamp with HAM-RS2 ( P=0.001 ) . Fasting triglyceride ( TG ) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 ( P=0.039 and P=0.027 respectively ) . Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption ( P=0.049 ) , postpr and ial GLP1 excursions during the MTT were significantly greater ( P=0.009 ) . HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM , but demonstrated beneficial effects on meal h and ling , possibly due to higher postpr and ial GLP1", "Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation , and to counteract systemic inflammation through a gut microbiota-mediated mechanism . Less is known about the properties of indigestible carbohydrates intrinsic to food . The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans . In all , twenty middle-aged subjects were provided with a barley kernel-based bread ( BB ) or a reference white wheat bread during 3 consecutive days , respectively , in a r and omised cross-over design study . At a st and ardised breakfast the following day ( day 4 ) , blood was collected for the analysis of blood ( b ) glucose regulation , gastrointestinal hormones , markers of inflammation and markers of colonic fermentation ; 3 d of intervention with BB increased gut hormones in plasma ( p ) the next morning at fasting ( p-glucagon-like peptide-1 ; 56 % ) and postpr and ially ( p-glucagon-like peptide-2 ; 13 % and p-peptide YY ; 18 % ) . Breath H₂ excretion and fasting serum ( s ) SCFA concentrations were increased ( 363 and 18 % , respectively ) , and b-glucose ( 22 % ) and s-insulin responses ( 17 % ) were decreased after BB intervention . Insulin sensitivity index ( ISI(composite ) ) was also improved ( 25 % ) after BB . In conclusion , 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation , metabolic control and maintenance of gut barrier function , as well as improved markers of glucose homoeostasis in middle-aged subjects , altogether relevant for the prevention of obesity and the metabolic syndrome", "Improvement of insulin resistance and inflammation is a basic strategy in the management of type 2 diabetes . There is limited evidence that prebiotics improve insulin resistance and inflammation . However , the ameliorating effect of resistant dextrin , as a prebiotic , on insulin resistance and inflammation in patients with type 2 diabetes has not been investigated so far . Therefore , the present study aim ed to examine the effects of resistant dextrin on insulin resistance and inflammation in type 2 diabetic patients . In a r and omised controlled clinical trial , fifty-five women with type 2 diabetes were assigned to two groups : the intervention group ( n 30 ) and the control group ( n 25 ) . The intervention group received a daily supplement of 10 g resistant dextrin and the control group received a similar amount of maltodextrin as placebo for 8 weeks . Fasting plasma glucose ( FPG ) , HbA1c , insulin , high-sensitivity C-reactive protein ( hs-CRP ) , IL-6 , TNF-α , malondialdehyde ( MDA ) and serum endotoxin concentrations were measured before and after the intervention . Data were analysed using SPSS ( version 13 ) . Paired and unpaired t tests and ANCOVA were used to compare quantitative variables after the intervention . Patients supplemented with resistant dextrin exhibited a significant decrease in fasting insulin ( 20.1 pmol/l , 22.8 % ) , homeostasis model assessment of insulin resistance ( 1.3 , 24.9 % ) , quantitative insulin sensitivity check index ( 0.2 , 7.2 % ) , IL-6 ( 1.4 pg/ml , 28.4 % ) , TNF-α ( 5.4 pg/ml , 18.8 % ) , MDA ( 1.2 nmol/ml , 25.6 % ) and endotoxin ( 6.2 endotoxin units/ml , 17.8 % ) concentrations than those supplemented with maltodextrin ( P in FPG ( 0.05 mmol/l , 0.6 % ) , HbA1c ( 0.5 % , 9.6 % ) and hs-CRP ( 2.7 ng/ml , 35.1 % ) concentrations in the resistant dextrin group were not significant when compared with the maltodextrin group . In conclusion , resistant dextrin supplementation can modulate inflammation and improve insulin resistance in women with type 2 diabetes", "BACKGROUND Type 2 diabetes ( T2D ) incidence continues to rise . Although increasing dietary fiber intake is an established strategy for improved glycemic control , most adults consume insufficient amounts . Fiber-enhanced functional foods can increase fiber intake , and there is particular interest in resistant starch ( RS ) as a high-fiber ingredient . Studies show that high-amylose maize resistant starch , type 2 ( HAM-RS2 ) improves acute and chronic glycemic responses , but more studies are needed in individuals at high risk of T2D with RS delivered in commonly consumed foods . OBJECTIVE The objective of this study was to examine the chronic effects of consuming bagels high in HAM-RS2 on fasting and postpr and ial glycemic markers in adults at increased risk of T2D . METHODS With the use of a r and omized , double-blind crossover design , 24 men and women with a mean ± SE age of 55.3 ± 1.59 y and body mass index ( in kg/m2 ) of 30.2 ± 0.57 consumed 1 bagel containing 25 g HAM-RS2/d or 1 control wheat bagel/d for 56 d each , separated by a 4-wk washout . Fasting and postpr and ial oral-glucose-tolerance test ( OGTT ) glucose and insulin were measured on study days 1 and 57 of each bagel treatment . RESULTS The RS bagel treatment result ed in significantly lower fasting ( 22.1 % , P = 0.04 ) , 2-h ( 23.3 % , P 0.05 ) insulin incremental areas under the curve and fasting insulin resistance ( homeostasis model assessment of insulin resistance ; 23.1 % , P = 0.04 ) than did the control bagel treatment . Fasting and postpr and ial OGTT glucose concentrations did not differ between the RS and control bagel treatments on study days 1 or 57 . CONCLUSIONS These data suggest that consumption of a high-HAM-RS2 bagel improves glycemic efficiency by reducing the amount of insulin required to manage postpr and ial glucose while improving fasting insulin sensitivity in adults at increased risk of T2D . This research provides support for a feasible dietary strategy for T2D risk reduction . This trial was registered at clinical trials.gov as NCT02129946", "Aims : This trial aims to determine the effects of resistant starch ( RS ) subtype 2 ( RS2 ) on glycemic status , metabolic endotoxemia and markers of oxidative stress . Methods : A r and omized , controlled , parallel-group clinical trial group of 56 females with type 2 diabetes mellitus ( T2DM ) was divided to 2 groups . The intervention group ( n = 28 ) and control group ( n = 28 ) received 10 g/day RS2 or placebo for 8 weeks , respectively . Fasting blood sample s were taken to determine glycemic status , endotoxin , high sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde ( MDA ) , total antioxidant capacity ( TAC ) , antioxidant enzymes concentrations as well as uric acid at baseline and after the intervention . Results : After 8 weeks , RS2 caused a significant decrease in the levels of MDA ( -34.10 % ) , glycosylated hemoglobin ( -9.40 % ) , insulin ( -29.36 % ) , homeostasis model of insulin resistance ( -32.85 % ) and endotoxin ( -25.00 % ) , a significant increase in TAC ( 18.10 % ) and glutathione peroxidase ( 11.60 % ) as compared with control . No significant changes were observed in fasting plasma glucose , quantitative insulin sensitivity check index , hs-CRP , superoxide dismutase , catalase and uric acid in the RS2 group as compared with the control group . Conclusion : Supplementation with RS2 may be improved glycemic status , endotoxemia and markers of oxidative stress in patients with T2DM", "OBJECTIVE We aim ed to evaluate whether 4-week of dietary treatment with rice containing resistant starch reduces blood glucose and oxidative stress as well as improves endothelial function . METHODS Patients with impaired fasting glucose ( IFG ) , impaired glucose tolerance ( IGT ) or newly diagnosed type 2 diabetes ( n = 90 ) were r and omly assigned to either a group ingesting rice containing 6.51 g resistant starch daily or a control rice group for 4-weeks . We assessed fasting and postpr and ial levels of glucose and insulin , oxidative stress markers and endothelial function using reactive hyperemia peripheral arterial tonometry ( RH-PAT ) . RESULTS The diet containing rice with resistant starch reduced fasting insulin and insulin resistance , postpr and ial glucose ( P = 0.010 ) and insulin levels at 30 min , and glucose and insulin areas under the response curve after the st and ard meal . Rice with resistant starch also decreased urinary 8-epi-PGF(2α ) and plasma malondialdehyde ( MDA ) and increased the RH-PAT index ( P and areas under the glucose response curve , MDA , RH-PAT , and total NO of the test group differed significantly from those in the control even after adjusting for baseline values . Overall , changes in the RH-PAT index correlated positively with changes in total NO ( r = 0.336 , P = 0.003 ) and superoxide dismutase activity ( r = 0.381 , P = 0.001 ) and negatively with changes in MDA ( r = -0.358 , P = 0.002 ) and 8-epi-PGF(2α ) . CONCLUSIONS In patients with IFG , IGT or newly diagnosed type 2 diabetes , 4-weeks of dietary treatment with rice containing resistant starch was associated with improved endothelial function with reduction of postpr and ial glucose and oxidative stress compared with control", "Aims /hypothesisDiets rich in insoluble-fibre are linked to a reduced risk of both diabetes and cardiovascular disease ; however , the mechanism of action remains unclear . The aim of this study was to assess whether acute changes in the insoluble-fibre ( resistant starch ) content of the diet would have effects on postpr and ial carbohydrate and lipid h and ling . Methods Ten healthy subjects consumed two identical , low-residue diets on separate occasions for 24 h ( 33 % fat ; resistant starch ( Novelose 260 ) . On the following morning a fibre-free meal tolerance test ( MTT ) was carried out ( 59 g carbohydrate ; 21 g fat ; 2.1 kJ ) and postpr and ial insulin sensitivity ( SIORAL ) assessed using a minimal model approach . Results Prior resistant starch consumption led to lower postpr and ial plasma glucose ( p=0.037 ) and insulin ( p=0.038 ) with a higher insulin sensitivity(44±7.5 vs 26±3.5 × 10−4 dl kg−1 min−1 per µUml−1 ; p=0.028 ) and C-peptide-to-insulin molar ratio ( 18.7±6.5 vs 9.7±0.69 ; p=0.017 ) . There was no effect of resistant starch consumption on plasma triacylglycerol although non-esterified fatty acid and 3-hydroxybutyrate levels were suppressed 5 h after the meal tolerance test . Conclusion Prior acute consumption of a high-dose of resistant starch enhanced carbohydrate h and ling in the postpr and ial period the following day potentially due to the increased rate of colonic fermentation", "OBJECTIVE The aim of the present study was to determine effects of Resistant Starch ( RS2 ) on metabolic parameters and inflammation in women with type 2 diabetes ( T2DM ) . METHODS In this r and omized controlled clinical trial , 60 females with T2DM were divided into intervention ( n = 28 ) and placebo groups ( n = 32 ) . They received 10 g/d RS2 or placebo for 8 weeks , respectively . Fasting blood sugar ( FBS ) , glycated hemoglobin ( HbA1c ) , lipid profile , high-sensitive C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-α ) were measured at baseline and at the end of the trial . Paired t test , unpaired t-test and ANCOVA were used to compare the quantitative variables . The data were analyzed using SPSS software version 13.0 . RESULTS RS2 decreased HbA1c ( -0.3 % , -3.6 % ) , TNF-α ( -3.4 pg/mL , -18.9 % ) , triglyceride ( -33.4 mg/dL , -15.4 % ) , and it increased HDL-c ( + 9.4 mg/dL , + 24.6 % ) significantly compared with the placebo group ( p were not significant in the RS2 group compared with the control group . RS2 can improve glycemic status , inflammatory markers and lipid profile in women with T2DM . CONCLUSIONS Although findings of the present study indicated positive effects of RS2 on inflammation and metabolic parameters , more studies are needed to confirm efficacy of RS2 as an adjunct therapy in diabetes" ]

[ "Our objective was to investigate the effects of iron depletion on adaptation to aerobic exercise , assessed by time to complete a 15-km cycle ergometer test . Forty-two iron-depleted ( serum ferritin 12 g/dl ) women ( 18 - 33 yr old ) received 100 mg of ferrous sulfate ( S ) or placebo ( P ) per day for 6 wk in a r and omized , double-blind trial . Subjects trained for 30 min/day , 5 days/wk at 75 - 85 % of maximum heart rate for the final 4 wk of the study . There were no group differences in baseline iron status or in 15-km time . Iron supplementation increased serum ferritin and decreased transferrin receptors in the S compared with the P group . The S and P groups decreased 15-km time and respiratory exchange ratio and increased work rate during the 15-km time trial after training . The decrease in 15-km time was greater in the S than in the P group ( P = 0.04 ) and could be partially attributed to increases in serum ferritin and Hb . These results indicate that iron deficiency without anemia impairs favorable adaptation to aerobic exercise ", "BACKGROUND Iron deficiency without anemia has been shown to reduce both muscle-tissue oxidative capacity and endurance in animals . However , the consequences of iron deficiency in humans remain unclear . OBJECTIVE We investigated the effects of iron supplementation on adaptation to aerobic training among marginally iron-depleted women . We hypothesized that iron supplementation for 6 wk would significantly improve iron status and maximal oxygen uptake ( VO(2)max ) after 4 wk of concurrent aerobic training . DESIGN Forty-one untrained , iron-depleted , nonanemic women were r and omly assigned to receive either 50 mg FeSO(4 ) or a placebo twice daily for 6 wk in a double-blind trial . All subjects trained on cycle ergometers 5 d/wk for 4 wk , beginning on week 3 of the study . RESULTS Six weeks of iron supplementation significantly improved serum ferritin and serum transferrin receptor ( sTfR ) concentrations and transferrin saturation without affecting hemoglobin concentrations or hematocrit . Average VO(2)max and maximal respiratory exchange ratio improved in both the placebo and iron groups after training ; however , the iron group experienced significantly greater improvements in VO(2)max . Both iron-status and fitness outcomes were analyzed after stratifying by baseline sTfR concentration ( > and sTfR status impairs aerobic adaptation among previously untrained women and that this can be corrected with iron supplementation", "BACKGROUND We previously showed that iron supplementation significantly improves iron status and maximal work capacity in previously untrained , marginally iron-deficient women with a baseline serum transferrin receptor concentration > 8.0 mg/L. However , the effect of transferrin receptor status on adaptation in endurance capacity after aerobic training in these subjects has not been fully explored . OBJECTIVE Our objective was to examine the effect of baseline serum transferrin receptor status on adaptations in endurance capacity . DESIGN Forty-one untrained , iron-depleted , nonanemic women were r and omly assigned to receive either 100 mg FeSO(4 ) or a placebo for 6 wk in a double-blind trial . All subjects trained on cycle ergometers 5 d/wk for the last 4 wk of the study . Endurance capacity was assessed at baseline and after treatment by using a 15-km time trial conducted on a cycle ergometer . RESULTS Significant treatment effects were observed for time to complete the 15-km time trial , work rate , and percentage of maximal oxygen uptake in subjects with a baseline serum transferrin receptor concentration > 8.0 mg/L. No significant treatment effects were observed in subjects with a normal baseline transferrin receptor concentration . CONCLUSIONS Our findings suggest that , in the presence of overt tissue iron deficiency , iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women . This impairment can be corrected with iron supplementation", "Eighty iron-deficient , nonpregnant female workers were r and omly assigned to ferrous sulphate ( 60 or 120 mg Fe/d ) or placebo treatment for 12 wk . Energy expenditure was estimated during 3 d by heart rate ( HR ) recording . Production efficiency ( PE ) was calculated as the ratio of productivity to energy expenditure . In the iron-treated group mean hemoglobin ( Hb ) increased from 114 to 127 g/L ( P serum ferritin increased from 9.7 to 30.0 micrograms/L ( P free erythrocyte protoporphyrin decreased from 1.01 to 0.49 mumol/L ( P Mean HR at work decreased from 95.5 to 91.1 beats/min ( P PE increased significantly in the iron-treated group ( P work at a lower energy cost", "Studies in laboratory animals found that iron deficiency without anemia decreased oxidative capacity and increased reliance on carbohydrate as the substrate for energy , thereby causing impaired endurance . The purpose of this cross-sectional study was to investigate the relation between iron deficiency without anemia and physical performance in healthy active women aged 19 - 36 y. Iron-status assessment included determination of hemoglobin , hematocrit , transferrin saturation , and serum ferritin values . Dietary iron intake was assessed by frequency question naires and physical activity level was estimated by frequency question naires and 2-wk records . Fifteen women with normal iron status and 15 women with iron depletion ( serum ferritin and given physical-performance tests , including determinations of maximum oxygen consumption ( VO2max ) , ventilatory threshold , and delta-efficiency . There were no significant differences between the two groups in body size , body composition , physical activity level , dietary iron intake , delta-efficiency , or ventilatory threshold . Compared with the iron-depleted group , the iron-sufficient group had significantly higher hemoglobin , transferrin saturation , and serum ferritin values and a significantly greater tendency to use iron supplements . When physical activity level and fat-free mass were controlled for , the iron-depleted group had a significantly lower VO2max . The difference in VO2max was significantly associated with serum ferritin concentration ; hemoglobin value was not a significant confounder . Therefore , reduction of VO2max in nonanemic women with iron depletion was likely caused by factors related to reduced body iron storage but was unrelated to decreased oxygen-transport capacity of the blood", "BACKGROUND Tissue iron depletion may negatively affect endurance performance and muscle fatigability . OBJECTIVE We investigated tissue-level iron depletion and progressive fatigue of the quadriceps during dynamic knee-extension exercise in young women . DESIGN Twenty iron-depleted ( serum ferritin 110 g/L ) women ( macro x + /- SEM age : 29.1 + /- 1.2 y ) received iron ( iron group ) or placebo ( placebo group ) for 6 wk in a r and omized , double-blind trial ( n = 10 per group ) . A protocol integrating 2 - 3-s maximal voluntary static contractions ( MVCs ) with dynamic knee extensions was used to assess fatigue . RESULTS No significant differences between the groups in baseline iron status , MVC at rest , or MVC at the end of the protocol were observed . After treatment , serum iron and transferrin saturation increased significantly in the iron group ( P = 0.02 and P = 0.03 , respectively ) . Serum transferrin receptor concentrations increased significantly in the placebo group ( P MVC was attenuated in the iron group but not in the placebo group ( P = 0.01 ) . In the iron group , MVC at the sixth minute of the fatigue protocol and MVC at the end of the protocol were approximately 15 % ( P = 0.04 ) and approximately 27 % higher ( P iron-status indexes or tissue iron stores , although power was low ( muscle fatigability . Interpretation regarding the direct role of tissue iron status is limited by the study 's low power to detect relations between tissue iron improvement and decreased muscle fatigue", "Forty-seven previously sedentary women participating in a 12-wk moderate aerobic-exercise program were r and omly assigned to one of four dietary groups : 50-mg/d iron supplement and a low food-iron diet ( 50 FE + EX ) , 10-mg/d iron supplement and a low food-iron diet ( 10 FE + EX ) , placebo and unrestricted diet ( P + EX ) , and meat supplement and high food-iron diet ( M + EX ) . A sedentary control group ( n = 13 ) received no dietary interventions . Hematocrit , total iron-binding capacity , and hemoglobin , serum iron , serum ferritin , and serum albumin concentrations were measured every 4 wk . Hemoglobin values decreased at the end of 4 wk in all exercising groups compared with the control group . Iron status in the 50 FE + EX and M + EX groups improved after week 4 as indicated by an increase in serum ferritin , serum iron , and hemoglobin concentrations , and a decline in total iron-binding capacity . Thus , short-term , moderate aerobic exercise result ed in compromised iron status that was offset to varying degrees by ingesting iron or meat supplements . However , meat supplements were more effective in protecting hemoglobin and ferritin status than were iron supplements", "Background Iron deficiency without anemia is related to adverse symptoms that can be relieved by supplementation . Since a blood donation can induce such an iron deficiency , we investigated the clinical impact of iron treatment after a blood donation . Methods One week after donation , we r and omly assigned 154 female donors with iron deficiency without anemia , aged below 50 years , to a four-week oral treatment of ferrous sulfate versus a placebo . The main outcome was the change in the level of fatigue before and after the intervention . Aerobic capacity , mood disorder , quality of life , compliance and adverse events were also evaluated . Hemoglobin and ferritin were used as biological markers . Results The effect of the treatment from baseline to four weeks of iron treatment was an increase in hemoglobin and ferritin levels to 5.2 g/L ( P fatigue ( -0.15 points , 95 % confidence interval -0.9 points to 0.6 points , P = 0.697 ) or for other outcomes . Compliance and interruption for side effects was similar in both groups . Additionally , blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces . Conclusions These data are valuable as they enable us to conclude that donors with iron deficiency without anemia after a blood donation would not clinical ly benefit from iron supplementation . Trial Registration Clinical Trials.gov :", "PURPOSE The purpose of this study was to find out whether iron repletion leads to an increase in red blood cell volume ( RBV ) and performance capacity in iron-deficient nonanemic athletes . METHODS 40 young elite athletes ( 13 - 25 yr ) with low serum ferritin ( 13.5 g.dL-1 , females > 11.7 g.dL-1 ) were r and omly assigned to 12-wk treatment with either twice a day ferrous iron ( equivalent to 2 x 100 mg elemental iron ) or with placebo using a double blind method . Before and after treatment , hematological measures and parameters of iron status were determined in venous blood . RBV , blood volume ( BV ) , and plasma volume ( PV ) were measured by CO rebreathing . For determination of the aerobic and anaerobic capacity ( maximal accumulated oxygen deficit , MAOD ) , the athletes performed an incremental as well as a highly intensive treadmill test . RESULTS After 12 wk , ferritin levels were within the normal range in the iron-treated group ( IG ) with a significant ( P RBV did not change significantly in either group nor did any of the hematological measures . However , only in IG there were significant increases in VO2max and in O2 consumption in the MAOD test . MAOD and maximal capillary lactate concentration remained unchanged in both treatment groups . CONCLUSIONS The results indicate that in young elite athletes with low serum ferritin and normal hemoglobin concentration iron supplementation leads to an increase in maximal aerobic performance capacity without an augmentation of RBV", " In 781 female college students , there were 41 cases of iron deficiency anemia , 209 of latent iron deficiency , 3 of other anemias , and 528 normal cases . Fifty-four volunteers recruited from the iron deficiency anemia and severe latent iron deficiency groups were r and omly divided into 4 study groups . Groups I and III received 500 mg of vitamin C daily , and groups II and IV received ferric ammonium citrate ( FeAC ; equivalent to 6 mg iron ) in addition to vitamin C for 9 weeks . Groups I and II were loaded by aerobic exercise at 50 % VO2 max . Significant differences between groups were noted in serum ferritin ( SF ) in III/IV , hematocrit ( Ht ) in II/III and III/IV , and reticulocytes ( RET ) in I/II , I/IV , and III/IV . Hemoglobin ( Hb ) and other iron-related blood indices tended to normalize in groups II and IV when compared with the pre-values . VO2 max was elevated in groups I and II regardless of iron treatment , but was augmented more in group II than group", "The purpose of this investigation was to examine the effects of oral iron supplementation on endurance performance in initially iron-depleted , nonanemic female distance runners . Eighteen iron-depleted ( serum ferritin less than 20 ng.ml-1 , hemoglobin greater than or equal to 12 g.dl-1 ) women ( 22 - 39 yr ) performed a VO2max test and an endurance run to exhaustion . Subjects were pair-matched on the basis of endurance time and then r and omly assigned to an iron supplement or a placebo group . Following supplementation , the iron group had a significantly higher ( P = 0.03 ) mean serum ferritin concentration ( 23.4 vs 15.7 ng.ml-1 ) and lower ( P = 0.04 ) mean total iron-binding capacity than the placebo group . Both groups increased their time to exhaustion ( 25.5 % and 22.2 % for the iron and placebo groups , respectively ) but were not significantly different ( P = 0.72 ) from each other . There were also no differences ( P greater than 0.05 ) between the groups with respect to lactate concentrations and physiological measures taken during the two exercise tests . The results of this study suggest that 8 wk of oral iron supplementation improves iron status in iron-depleted female distance runners , but does not enhance endurance capacity", "We studied the effect of 2 weeks of iron therapy on exercise performance and exercise-induced lactate production in trained women athletes : six control subjects with normal parameters of iron status and nine with mild iron-deficiency anemia defined by low Fe/TIBC , ferritin , and minimally decreased Hgb values . Iron therapy improved the abnormal measures of iron status and low Hgb in the second group to normal . Exercise performance in a progressive work-exercise protocol on a bicycle ergometer to exhaustion was unchanged after iron therapy in both groups ; however , blood lactate levels at maximum exercise in the iron-deficient group decreased significantly from 10.3 + /- 0.6 mmol/L before therapy to 8.42 + /- 0.7 after therapy ( p less than 0.03 ) . The control subjects did not significantly alter lactate levels after maximal exercise on iron compared to placebo : 8.3 + /- 0.8 mmol/L vs. 8.5 + /- 0.7 . Although there was not a significant difference in maximum exercise performance after iron therapy , these data support animal experiments implying that iron may play a role in oxidative metabolism and that minimal decreases in Hgb may impair arterial oxygen content enough to affect aerobic metabolism . In addition , these findings may have important implication s for competitive women athletes in whom mild iron deficiency may go unnoticed", "Objective : To determine the effect of iron supplementation on iron status and endurance capacity . Design : R and omized , double-blind iron supplementation . Setting : University of Missouri-Columbia and surrounding community . Subjects : Twenty iron-deficient ( serum ferritin , sFer8.0 mg/l ; or sTfR/log sFer index > 4.5 ) , nonanemic ( hemoglobin , Hb>120 g/l , women ; > 130 g/l , men ) men and women ( 18–41 years ) were recruited via fliers and newspaper advertisements ; 20 of 31 eligible subjects participated . Interventions : A 30 mg measure of elemental iron as ferrous sulfate or placebo daily for 6 weeks . Results : Dietary iron intake and physical activity did not differ between groups before or after supplementation . Iron supplementation significantly increased sFer compared to placebo ( P=0.01 ) , but did not affect Hb or hematocrit . Iron supplementation prevented the decline in ventilatory threshold ( VT ) observed in the placebo group from pre- to post-supplementation ( P=0.01 ) ; this effect was greater in individuals with lower sFer before intervention ( P . Changes in sFer from pre- to post-treatment were positively correlated with changes in VT ( P=0.03 ) , independent of supplementation . The iron group significantly increased gross energetic efficiency during the submaximal test ( P=0.04 ) . Changes in sFer were negatively correlated with changes in average respiratory exchange ratio during the submaximal test ( P Conclusions : Iron supplementation significantly improves iron status and endurance capacity in iron-deficient , nonanemic trained male and female subjects . Sponsorship : Missouri University Alumni Association , by the Elizabeth Hegarty Foundation and by the Department of Nutritional Sciences", "Summary Serum iron deficiency has a high incidence in female athletes . We investigated the effects of a daily oral iron supplement , ( 160 mg ) administered during an intensive 7-week physical training programme , on body iron status , and the maximal aerobic capacity ( VO2max ) of 13 women ( group A ) compared to 15 who took a placebo ( group B ) . The subjects were 19 years old . Blood sample s were obtained before training began and on days 1 , 7 , 21 and 42 of training . They were analysed for packed cell volume ( PVC ) and for haemoglobin ( Hb ) , 2,3-diphosphoglycerate ( 2,3-DPG ) , haptoglobin , iron and ferritin concentrations . TheVO2max was measured on days 0 , 21 and 42 of training . Following 21 days of training Hb , PCV and ferritin were significantly higher ( P⩽0.01 ) in group A compared to group B. Over the training period Hb rose by 9.3 % and 2.4 % in groups A and B , respectively . At the end of training 66 % of group B exhibited ferritin concentrations below 10 ng·ml−1 , while none of group A had such low values . MeanVO2max of group A had increased by 7.5 % following 21 days of training ( P⩽0.01 ) and by 15.3 % after 42 days . No appreciable increase inVO2max had occurred in group B by day 21 ( significantly lower thanVO2max of group A;P⩽0.05 ) , however by day 42 it had increased by 14.3 % ( P⩽0.05 ) . In both groups 2,3-DPG·g Hb−1 had increased significantly ( P⩽0.005 ) by day 7 ( 22 % ) and remained at that level for an additional 35 days . We concluded that a daily oral iron supplement given to young women during intensive training improved several haematological variables and their body iron status . This improvement was associated with an increasedVO2max only during the early stages of their training ( day 21 ) compared with the placebo group", "Serum transferrin receptor ( sTfR ) concentration has been recognized recently as a reliable indicator of functional iron deficiency , but its response to iron supplementation has not been investigated in marginally iron-deficient women . In this r and omized , double-blinded trial , 37 female subjects aged 19 - 35 y with iron depletion without anemia ( hemoglobin > 120 g/L and serum ferritin received an iron supplement or placebo for 8 wk . Iron status was measured before treatment , after 4 wk of treatment , and posttreatment ( ie , after 8 wk of treatment ) . Iron supplementation of these iron-depleted , nonanemic women result ed in a progressive and significant decrease in sTfR and a significant increase in serum ferritin , and prevented a fall in hemoglobin . The responsiveness of sTfR to iron treatment indicated that sTfR is a sensitive indicator of marginal iron deficiency in iron-depleted , nonanemic women , even when their body iron stores were being replenished", "To determine the effects of an 8-wk dietary iron supplementation ( 100 mg.d-1 ) on low plasma ferritin concentration ( 20 active women ( 19 - 35 yr ) were studied while performing a VO2max test and an endurance test ( 80 % VO2max ) on a cycle ergometer . Subjects were r and omly placed in an iron supplement ( IG ) or a placebo group ( PG ) using a double-blind method . After treatment in the IG , ferritin levels were higher ( 22.5 + /- 3.4 vs 14.3 + /- 2.2 ng.ml-1 ; P Hb increased ( 12.8 + /- 0.4 to 14.1 + /- 0.2 g.dl-1 ; P TIBC decreased ( 366.2 + /- 24.8 to 293.8 + /- 14.0 micrograms.dl-1 ; P IG 's VO2max was significantly greater ( P postendurance blood lactate decreased ( 5.03 + /- 0.44 to 3.85 + /- 0.6 mM.l-1 ; P Endurance time to exhaustion increased 38 % ( 37.28 + /- 5.03 to 51.4 + /- 7.45 min ) following iron treatment ; however , this change was not statistically significant . The results suggest that this level of iron supplementation can reverse mild anemia , increase VO2max , and reduce blood lactate concentration after submaximal exercise", "The purpose of this study was to determine the effects of two weeks of high dosage iron supplementation on various blood iron indices and metabolic parameters in non-anemic , iron-depleted competitive female cross-country runners . The subjects were highly trained members of the Colorado State University cross-country team and were completing 40 to 50 miles of training weekly . A pretest , post-test single-blind crossover design was employed . Upon collection of baseline exercise blood and metabolic data , five subjects were r and omly assigned to iron supplementation ( 650 mg ferrous sulfate ; 130 mg elemental iron ) and five subjects to placebo treatment . At two weeks the treatments were reversed . Exercise blood and metabolic data were collected at two-week intervals . Dietary iron intake was assessed using a three-day dietary survey . Dietary analysis revealed deficiencies in vitamin B-6 , iron , magnesium , and zinc according to USRDA st and ards . Baseline blood sample s revealed no deficiencies in iron storage or transport proteins . Two weeks of iron supplementation result ed in no significant increases in blood iron indices . Metabolic parameters related to running performance were also unchanged after iron supplementation . High dosage , short-term iron supplementation appears to have no effect on blood or metabolic parameters in iron-depleted but non-anemic female cross-country runners", "Iron supplementation strategies in the developing world remain controversial because of fears of exacerbating prevalent infectious diseases . Underst and ing the conditions in which iron will be absorbed and incorporated into erythrocytes is therefore important . We studied Gambian children with either postmalarial or nonmalarial anemia , who were given oral iron supplements daily for 30 days . Supplements administered on days 1 and 15 contained the stable iron isotopes 57Fe and 58Fe , respectively , and erythrocyte incorporation was measured in blood sample s drawn 14 days later . We investigated how the iron-regulatory hormone hepcidin and other inflammatory/iron-related indices , all measured on the day of isotope administration , correlated with erythrocyte iron incorporation . In univariate analyses , hepcidin , ferritin , C-reactive protein , and soluble transferrin receptor ( sTfR ) strongly predicted incorporation of 57Fe given on day 1 , while hepcidin , ferritin , and sTfR/log ferritin correlated with 58Fe incorporation . In a final multivariate model , the most consistent predictor of erythrocyte isotope incorporation was hepcidin . We conclude that under conditions of competing signals ( anemia , iron deficiency , and infection ) , hepcidin powerfully controls use of dietary iron . We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world", "Low serum ferritin concentrations are commonly found in female athletes . By study ing the effects of an 8-week iron or placebo supplementation in 31 female athletes ( aged 17 - 31 years ) , with an initial serum ferritin concentration less than or equal to 25 micrograms/l and blood hemoglobin 120 g/l , we investigated whether low serum ferritin values hinder aerobic performance . Serum ferritin concentration increased from 14 ( 25th and 75th percentile : 11 , 21 ) to 26 ( 18 , 36 ) micrograms/l in the iron-supplemented group , but remained at a low 11 ( 9 , 17 ) micrograms/l in the placebo group ( group difference after supplementation : p = 0.001 ) . Before supplementation , blood hemoglobin concentration was not different in the two groups . After supplementation , however , the concentration in the iron group was 139 ( 135 , 144 ) g/l and 128 ( 126 , 134 ) g/l in the placebo group ( group difference : p = 0.001 ) . Iron supplementation did not affect blood lactate concentration or VO2max during an incremental ergometer test . Hence , aerobic performance was not impaired in nonanemic female athletes with serum ferritin 25 micrograms/l", "Iron-deficiency anemia impairs exercise capacity , but whether nonanemic iron depletion decreases endurance performance is unclear . In 14 iron-deficient ( serum ferritin level , less than 20 micrograms/L [ less than 20 ng/L])nonanemic runners , hematologic and treadmill running values were followed up during a competitive season . Following a four-week control period , runners were treated for one month in a double-blind protocol with ferrous sulfate ( 975 mg/d ) or placebo . During treatment , the mean ferritin level rose from 8.7 to 26.6 micrograms/L ( 8.7 to 26.6 ng/mL ) in those patients taking iron and fell from 10.6 to 8.6 micrograms/L ( 10.7 to 8.6 ng/mL ) in the placebo group . Treadmill endurance times improved significantly in the iron-treated runners compared with controls . Endurance time declined in all seven controls ( range , 0.07 to 1.30 minutes ) , while six of seven iron-treated subjects improved their performance ( range , 0.03 to 1.92 minutes ) . No significant differences in maximal or submaximal oxygen consumption , ventilation , or heart rate were observed between the groups except for a 4 % increase in maximum oxygen consumption during placebo treatment . These data indicate that nonanemic iron deficiency impairs exercise performance but does not influence gas exchange or cardiac measures", "BACKGROUND Decrements in iron status have been reported in female soldiers during military training . Diminished iron status adversely affects physical and cognitive performance . OBJECTIVE We wanted to determine whether iron supplementation could prevent decrements in iron status and improve measures of physical performance and cognitive status in female soldiers during basic combat training ( BCT ) . DESIGN In this 8-wk r and omized , double-blind , placebo-controlled trial , soldier volunteers ( n = 219 ) were provided with capsules containing either 100 mg ferrous sulfate or a placebo . Iron status indicator assays were performed pre- and post-BCT . Two-mile running time was assessed post-BCT ; mood was assessed by using the Profile of Mood States question naire pre- and post-BCT . RESULTS The BCT course affected iron status : red blood cell distribution width and soluble transferrin receptor were elevated ( P serum ferritin was lowered ( P iron status ; group-by-time interactions ( P serum ferritin and soluble transferrin receptor . Iron supplementation result ed in improved ( P vigor scores on the Profile of Mood States post-BCT and in faster running time ( P iron status in female soldiers . Furthermore , iron supplementation may prove to be beneficial for mood and physical performance during the training period . Future efforts should identify and treat female soldiers or athletes who begin training regimens with iron deficiency or iron deficiency anemia", "There was no significant change in the maximal oxygen uptake for either the experimental or the control group from the pre-test to the post-test . Five blood chemistry measures were unable to predict the post-maximal oxygen uptake scores using the procedure of stepwise regression . An examination of the blood chemistry profiles indicated that sports anemia did not occur . The factorial breakdown was unable to produce any significant insight into the changes in hemoglobin concentration and oxygen consumption . Heme-iron supplementation was unable to override the regulatory system of the body and allow the hemoglobin level to become elevated", "In order to examine the effects of mild iron deficiency on physical work capacity , 40 prelatent iron-deficient female endurance runners were studied before and after 8 wk of supplementation with either oral iron ( 320 mg ferrous sulfate ) or a matching placebo . Subjects underwent the following physical work capacity tests : the Wingate cycle ergometer test , the anaerobic speed test , the ventilatory threshold , VO2max , and maximal treadmill velocity during the VO2max test . Muscle biopsy sample s pre- and post-treatment were obtained from 17 of the subjects , and these were assayed for citrate synthase and cytoplasmic alpha-glycerophosphate dehydrogenase activity . Subjects were r and omly assigned to one of the treatment groups , and a double-blind method of administration of the supplements was used . The differences in improvement scores between the two groups on the work capacity and enzyme activity variables were statistically nonsignificant ( P greater than 0.05 ) . Serum ferritin values rose from a mean of 12.4 + /- 4.5 to 37.7 + /- 19.7 ng.ml-1 for the experimental group and from 12.2 + /- 4.3 to 17.2 + /- 8.9 ng.ml-1 for the controls ( P = 0.0025 ) , whereas hemoglobin levels remained fairly constant for both groups ( P = 0.6 ) . Eight weeks of iron supplementation to prelatent/latent iron-deficient , physically active females did not significantly enhance work capacity . Within the limitations of this study , the presence of a serum ferritin below 20 ng.ml-1 does not pose a significant h and icap to physical work capacity", "The effects of energy supplementation ( group I received 200 kcal/day and group II received 1000/kcal day ) were examined on road workers in Kenya . Anthropometric , dietary , worker productivity , clinical hematology , and parasitology data were collected from 224 workers of both sexes or , sub sample s of these workers at base-line , midpoint , and final measurement periods . Sixty-seven percent of the work force was less than 85 % of weight for height . Females tended to be better nourished than males . Multiple regression analysis showed that increases in arm circumference and Hb levels were associated with significant productivity gains of about 4 % . At the midpoint , group II males gained 1.10 kg ( p less than 0.0003 ) while group I males showed no change . Weight loss during the latter part of the study result ed in no significant final weight change for males . \" Successful \" supplementation was weakly associated with a productivity increase for group II workers of 12.5 % ( p less than 0.10 )", "The impact of long-term ( 6-month ) moderate exercise on the iron status of previously sedentary women was determined by r and omly assigning 62 college-age women into one of the following four groups : 1 ) 50 mg.d-1 iron supplement , low iron diet ( N = 16 ) ; 2 ) Placebo , free choice diet ( N = 13 ) ; 3 ) Meat supplement to achieve 15 mg.d-1 iron intake ( N = 13 ) ; and 4 ) Control , free choice diet ( N = 20 ) . All groups except the Control group exercised 3 d.wk-1 at 60%-75 % of their heart rate reserve . VO2max was measured at baseline and week 24 . Blood was sample d at baseline and every 4 wk thereafter for 24 wk to measure iron status and to eluci date the causes for alterations in iron status . Subjects had depleted iron stores throughout the study as indicated by their serum ferritin levels ( Serum iron , total iron binding capacity and transferrin saturation were not compromised with exercise . Mean hemoglobin level in the Placebo/Ex group was significantly ( P serum albumin , haptoglobin , and erythropoietin data from the study can not explain these changes" ]

[ "Objectives : Published preliminary findings from a r and omized-controlled trial suggest that an 8-week Yoga of Awareness intervention may be effective for improving symptoms , functional deficits , and coping abilities in fibromyalgia . The primary aims of this study were to evaluate the same intervention ’s posttreatment effects in a wait-list group and to test the intervention ’s effects at 3-month follow-up in the immediate treatment group . Methods : Unpaired t tests were used to compare data from a per protocol sample of 21 women in the immediate treatment group who had completed treatment and 18 women in the wait-list group who had completed treatment . Within-group paired t tests were performed to compare posttreatment data with 3-month follow-up data in the immediate treatment group . The primary outcome measure was the Fibromyalgia Impact Question naire Revised ( FIQR ) . Multilevel r and om-effects models were also used to examine associations between yoga practice rates and outcomes . Results : Posttreatment results in the wait-list group largely mirrored results seen at posttreatment in the immediate treatment group , with the FIQR Total Score improving by 31.9 % across the 2 groups . Follow-up results showed that patients sustained most of their posttreatment gains , with the FIQR Total Score remaining 21.9 % improved at 3 months . Yoga practice rates were good , and more practice was associated with more benefit for a variety of outcomes . Discussion : These findings indicate that the benefits of Yoga of Awareness in fibromyalgia are replicable and can be maintained", "Background There is increasing recognition of mindfulness and mindfulness training as a way to decrease stress and increase psychological functioning . Purpose The aims of this study were to examine the effects of mindfulness stress reduction training on perceived stress and psychological well-being and to examine if changes in mindfulness mediate intervention effects on these outcomes . Methods Seventy women and one man with a previous cancer diagnosis ( mean age 51.8 years , st and ard deviation = 9.86 ) were r and omized into an intervention group or a wait-list control group . The intervention consisted of an 8-week mindfulness training course . Results Compared to participants in the control group , participants in the mindfulness training group had significantly decreased perceived stress and posttraumatic avoidance symptoms and increased positive states of mind . Those who participated in the intervention reported a significant increase in scores on the five-facet mindfulness question naire ( FFMQ ) when compared to controls . The increase in FFMQ score mediated the effects of the intervention on perceived stress , posttraumatic avoidance symptoms , and positive states of mind . Conclusions This study indicates that the improvements in psychological well-being result ing from mindfulness stress reduction training can potentially be explained by increased levels of mindfulness as measured with the FFMQ . The importance of these findings for future research in the field of mindfulness is discussed", "Background : Mindfulness-based stress reduction ( MBSR ) proposes a systematic program for reduction of suffering associated with a wide range of medical conditions . Studies suggest improvements in general aspects of well-being , including quality of life ( QoL ) , coping and positive affect , as well as decreased anxiety and depression . Methods : A quasi-experimental study examined effects of an 8-week MBSR intervention among 58 female patients with fibromyalgia ( mean , 52 ± 8 years ) who underwent MBSR or an active social support procedure . Participants were assigned to groups by date of entry , and 6 subjects dropped out during the study . Self-report measures were vali date d German inventories and included the following scales : visual analog pain , pain perception , coping with pain , a symptom checklist and QoL. Pre- and postintervention measurements were made . Additionally , a 3-year follow-up was carried out on a subgroup of 26 participants . Results : Pre- to postintervention analyses indicated MBSR to provide significantly greater benefits than the control intervention on most dimensions , including visual analog pain , QoL subscales , coping with pain , anxiety , depression and somatic complaints ( Cohen d effect size , 0.40–1.10 ) . Three-year follow-up analyses of MBSR participants indicated sustained benefits for these same measures ( effect size , 0.50–0.65 ) . Conclusions : Based upon a quasi-r and omized trial and long-term observational follow-up , results indicate mindfulness intervention to be of potential long-term benefit for female fibromyalgia patients", "& NA ; Mindfulness‐based stress reduction ( MBSR ) is a structured 8‐week group program teaching mindfulness meditation and mindful yoga exercises . MBSR aims to help participants develop nonjudgmental awareness of moment‐to‐moment experience . Fibromyalgia is a clinical syndrome with chronic pain , fatigue , and insomnia as major symptoms . Efficacy of MBSR for enhanced well‐being of fibromyalgia patients was investigated in a 3‐armed trial , which was a follow‐up to an earlier quasi‐r and omized investigation . A total of 177 female patients were r and omized to one of the following : ( 1 ) MBSR , ( 2 ) an active control procedure controlling for nonspecific effects of MBSR , or ( 3 ) a wait list . The major outcome was health‐related quality of life ( HRQoL ) 2 months post‐treatment . Secondary outcomes were disorder‐specific quality of life , depression , pain , anxiety , somatic complaints , and a proposed index of mindfulness . Of the patients , 82 % completed the study . There were no significant differences between groups on primary outcome , but patients overall improved in HRQoL at short‐term follow‐up ( P = 0.004 ) . Post hoc analyses showed that only MBSR manifested a significant pre‐to‐post‐intervention improvement in HRQoL ( P = 0.02 ) . Furthermore , multivariate analysis of secondary measures indicated modest benefits for MBSR patients . MBSR yielded significant pre‐to‐post‐intervention improvements in 6 of 8 secondary outcome variables , the active control in 3 , and the wait list in 2 . In conclusion , primary outcome analyses did not support the efficacy of MBSR in fibromyalgia , although patients in the MBSR arm appeared to benefit most . Effect sizes were small compared to the earlier , quasi‐r and omized investigation . Several method ological aspects are discussed , e.g. , patient burden , treatment preference and motivation , that may provide explanations for differences . In a 3‐armed r and omized controlled trial in female patients suffering from fibromyalgia , patients benefited modestly from a mindfulness‐based stress reduction intervention", "Customized foot orthotics are widely prescribed for patients with chronic , non-specific low back pain and lower limb pain , but there are few trials demonstrating effectiveness , and none for fibromyalgia . A total of 67consecutive patients presenting with chronic , widespread pain , who met the 1990 American College of Rheumatology criteria for fibromyalgia , were included in the study . A total of 32 subjects were prescribed a spinal exercise therapy program along with analgesics . These subjects formed the Control group . A second group , comprised of 35 subjects , received the same therapy , along with customized foot orthotics ( Orthotics group ) . All subjects completed the Revised Fibromyalgia Impact Question naire ( FIQR ) at the initiation of the study and at 8 weeks follow-up . The number of subjects using any type of prescription analgesic or other medication for chronic pain at baseline and at 8 weeks was also recorded . A total of 30 subjects in the Control group and 33 in the Orthotics group completed the study . All subjects completed the baseline and 8-week FIQR . The two groups were well matched in terms of age ( 45.3 ± 11.5 years in the Orthotics group vs. 47.2 ± 8.7 years in the cohort Control ) , medication use , duration of pain ( 6.5 ± 4.3 years in the Orthotics group vs. 6.2 ± 3.4 years in the cohort Control group ) , as well as baseline FIQR scores ( 55.2 ± 11.0 in the Orthotics group vs. 56.3 ± 12.2 in the cohort Control group ) . At 8 weeks , the Orthotics group had a greater reduction in the FIQR score than the cohort Control group ( reduction of 9.9 ± 5.9 vs. 4.3 ± 4.4 , respectively ) , and this was mainly due to changes in the ‘ function ’ domain of the FIQR ( reduction of 19.6 ± 9.4 in the Orthotics group vs. 8.1 ± 4.3 in the cohort Control group ) . As part of a complex intervention , in a cohort-controlled trial of primary care patients with fibromyalgia , the addition of custom-made foot orthotics to usual care appears to improve functioning in the short term", "OBJECTIVES To examine the effects of a challenge with monosodium glutamate ( MSG ) as compared to placebo on the symptoms of fibromyalgia ( FM ) , in participants who initially experienced > 30 % remission of symptoms on an excitotoxin elimination diet . METHODS Fifty-seven FM patients who also had irritable bowel syndrome ( IBS ) were placed on a 4-week diet that excluded dietary additive excitotoxins including MSG and aspartame . Thirty-seven people completed the diet and 84 % of those reported that > 30 % of their symptoms resolved , thus making them eligible to proceed to challenges . Subjects who improved on the diet were then r and omised to a 2-week double-blind placebo-controlled crossover challenge with MSG or placebo for 3 consecutive days each week . The primary outcome measure was total symptom score . Secondary outcome measures included visual analogue pain scales ( VAS for FM and IBS ) , an IBS Quality of Life Question naire ( IBS QOL ) and the Fibromyalgia Impact Question naire-Revised ( FIQR ) . Repeated measures ANOVA was used to analyse crossover challenge results . RESULTS The MSG challenge , as compared to placebo , result ed in a significant return of symptoms ( total symptom score , p worsening of fibromyalgia severity as determined by the FIQR ( p decreased quality of life in regards to IBS symptoms ( IBS QOL , p worsening FM pain based on visual analogue scale ( VAS , p<0.07 ) . CONCLUSIONS These findings suggest that dietary glutamate may be contributing to FM symptoms in some patients . Future research on the role of dietary excitotoxins in FM is warranted", "OBJECTIVE To test the short and longterm benefits of an 8 week mind-body intervention that combined training in mindfulness meditation with Qigong movement therapy for individuals with fibromyalgia syndrome ( FM ) . METHODS A total of 128 individuals with FM were r and omly assigned to the mind-body training program or an education support group that served as the control . Outcome measures were pain , disability ( Fibromyalgia Impact Question naire ) , depression , myalgic score ( number and severity of tender points ) , 6 minute walk time , and coping strategies , which were assessed at baseline and at 8 , 16 , and 24 weeks . RESULTS Both groups registered statistically significant improvements across time for the Fibromyalgia Impact Question naire , Total Myalgic Score , Pain , and Depression , and no improvement in the number of feet traversed in the 6 minute walk . However , there was no difference in either the rate or magnitude of these changes between the mind-body training group and the education control group . Salutary changes occurring by the eighth week ( which corresponded to the end of the mind-body and education control group sessions ) were largely maintained by both groups throughout the 6 month followup period . CONCLUSION While both groups showed improvement on a number of outcome variables , there was no evidence that the multimodal mind-body intervention for FM was superior to education and support as a treatment option . Additional r and omized controlled trials are needed before interventions of this kind can be recommended for treatment of FM", "Objectives Fibromyalgia syndrome ( FMS ) is a chronic disorder defined by widespread muscle pain and multiple tender points . The objectives of this study were to estimate prevalence of comorbidities , healthcare re sources utilization , and costs associated with FMS . Methods A retrospective cohort study was conducted using data from the Quebec provincial health plans ( RAMQ ) for a r and om sample of patients with diagnoses of FMS and a control cohort of patients without FMS , matched for age and gender . Prevalence of comorbidities was estimated . Healthcare re sources consumed by FMS and non-FMS patients were identified in terms of visits to physicians , physician 's interventions , pain-related medications , nonpain-related medications , and hospitalizations . Results A total of 16,010 patients with 2 diagnoses of FMS were identified , and control patients were r and omly selected with a ratio of 1:1 . Incidence of most comorbidities was significantly higher in the FMS group and the chronic disease score ( 3.8 vs. 2.8 ; ANOVA P The proportion of patients with at least 1 comorbidity was 87.4 % in the FMS group and 60.1 % in the control group ( χ2P The annual number of visits to physician and physician 's interventions was 25.1 for FMS and 14.8 for non-FMS patients . The amount paid by the RAMQ was significantly higher for patients with FMS ( $ 4065 ) compared with patients without FMS ( $ 2766 ) ( ANOVA P patients with a diagnosis of FMS and strongly indicate that the economic burden of FMS is substantial", "OBJECTIVE Depressive symptoms are common among patients with fibromyalgia , and behavioral intervention has been recommended as a major treatment component for this illness . The objective of this study was to test the effects of the Mindfulness-Based Stress Reduction ( MBSR ) intervention on depressive symptoms in patients with fibromyalgia . METHODS This r and omized controlled trial examined effects of the 8-week MBSR intervention on depressive symptoms in 91 women with fibromyalgia who were r and omly assigned to treatment ( n = 51 ) or a waiting-list control group ( n = 40 ) . Eligible patients were at least 18 years old , willing to participate in a weekly group , and able to provide physician verification of a fibromyalgia diagnosis . Of 166 eligible participants who responded to local television news publicizing , 49 did not appear for a scheduled intake , 24 enrolled but did not provide baseline data , and 2 were excluded due to severe mental illness , leaving 91 participants . The sample averaged 48 years of age and had 14.7 years of education . The typical participant was white , married , and employed . Patients r and omly assigned to treatment received MBSR . Eight weekly 2.5-hour sessions were led by a licensed clinical psychologist with mindfulness training . Somatic and cognitive symptoms of depression were assessed using the Beck Depression Inventory administered at baseline , immediately postprogram , and at followup 2 months after the conclusion of the intervention . RESULTS Change in depressive symptoms was assessed using slopes analyses of intervention effects over time . Depressive symptoms improved significantly in treatment versus control participants over the 3 assessment s. CONCLUSION This meditation-based intervention alleviated depressive symptoms among patients with fibromyalgia", "OBJECTIVE To conduct a feasibility and efficacy trial of mindfulness therapy in somatization disorder and functional somatic syndromes such as fibromyalgia , irritable bowel syndrome , and chronic fatigue syndrome , defined as bodily distress syndrome ( BDS ) . METHODS We r and omized 119 patients to either mindfulness therapy ( mindfulness-based stress reduction and some cognitive behavioral therapy elements for BDS ) or to enhanced treatment as usual ( 2-hour specialist medical care and brief cognitive behavioral therapy for BDS ) . The primary outcome measure was change in physical health ( SF-36 Physical Component Summary ) from baseline to 15-month follow-up . RESULTS The study is negative as we could not demonstrate a different development over time for the two groups ( F(3,2674)=1.51 , P=.21 ) . However , in the mindfulness therapy group , improvement was obtained toward the end of treatment and it remained present at the 15-month follow-up , whereas the enhanced treatment as usual group achieved no significant change until 15-month follow-up . The change scores averaged half a st and ard deviation which amounts to a clinical ly significant change , 29 % changed more than 1 st and ard deviation . Significant between-group differences were observed at treatment cessation . CONCLUSION Mindfulness therapy is a feasible and acceptable treatment . The study showed that mindfulness therapy was comparable to enhanced treatment as usual in improving quality of life and symptoms . Nevertheless , considering the more rapid improvement following mindfulness , mindfulness therapy may be a potentially useful intervention in BDS patients . Clinical ly important changes that seem to be comparable to a CBT treatment approach were obtained . Further research is needed to replicate or even exp and these findings" ]

[ "Objective : Stimulant medications , such as methylpheni date ( MPH ) , improve the academic performance of children with attention-deficit hyperactivity disorder ( ADHD ) . However , the mechanism by which MPH exerts an effect on academic performance is unclear . We examined MPH effects on math performance and investigated possible mediation of MPH effects by changes in time on-task , inhibitory control , selective attention , and reaction time variability . Methods : Children with ADHD aged 7 to 11 years ( N = 93 ) completed a timed math worksheet ( with problems tailored to each individual 's level of proficiency ) and 2 neuropsychological tasks ( Go/No-Go and Child Attention Network Test ) at baseline , then participated in a 4-week , r and omized , controlled , titration trial of MPH . Children were then r and omly assigned to their optimal MPH dose or placebo for 1 week ( administered double-blind ) and repeated the math and neuropsychological tasks ( posttest ) . Baseline and posttest videorecordings of children performing the math task were coded to assess time on-task . Results : Children taking MPH completed 23 more math problems at posttest compared to baseline , whereas the placebo group completed 24 fewer problems on posttest versus baseline , but the effects on math accuracy ( percent correct ) did not differ . Path analyses revealed that only change in time on-task was a significant mediator of MPH 's improvements in math productivity . Conclusions : MPH-derived math productivity improvements may be explained in part by increased time spent on-task , rather than improvements in neurocognitive parameters , such as inhibitory control , selective attention , or reaction time variability", "OBJECTIVE Methylpheni date ( MPH ) , the most commonly prescribed drug for attention-deficit/hyperactivity disorder ( ADHD ) , has a short half-life , which necessitates multiple daily doses . The need for multiple doses produces problems with medication administration during school and after-school hours , and therefore with compliance . Previous long-acting stimulants and preparations have shown effects equivalent to twice-daily dosing of MPH . This study tests the efficacy and duration of action , in natural and laboratory setting s , of an extended-release MPH preparation design ed to last 12 hours and therefore be equivalent to 3-times-daily dosing . METHODS Sixty-eight children with ADHD , 6 to 12 years old , participated in a within-subject , double-blind comparison of placebo , immediate-release ( IR ) MPH 3 times a day ( tid ) , and Concerta , a once-daily MPH formulation . Three dosing levels of medication were used : 5 mg IR MPH tid/18 mg Concerta once a day ( qd ) ; 10 mg IR MPH tid/36 mg Concerta qd ; and 15 mg IR MPH tid/54 mg Concerta qd . All children were currently medicated with MPH at enrollment , and each child 's dose level was based on that child 's MPH dosing before the study . The doses of Concerta were selected to be comparable to the daily doses of MPH that each child received . To achieve the ascending rate of MPH delivery determined by initial investigations to provide the necessary continuous coverage , Concerta doses were 20 % higher on a daily basis than a comparable tid regimen of IR MPH . Children received each medication condition for 7 days . The investigation was conducted in the context of a background clinical behavioral intervention in both the natural environment and the laboratory setting . Parents received behavioral parent training and teachers were taught to establish a school-home daily report card ( DRC ) . A DRC is a list of individual target behaviors that represent a child 's most salient areas of impairment . Teachers set daily goals for each child 's impairment targets , and parents provided rewards at home for goal attainment . Each weekday , teachers completed the DRC , and it was used as a dependent measure of individualized medication response . Teachers and parents also completed weekly st and ardized ratings of behavior and treatment effectiveness . To evaluate the time course of medication effects , children spent 12 hours in a laboratory setting on Saturdays and medication effects were measured using procedures and methods adapted from our summer treatment program . Measures of classroom behavior and academic productivity/accuracy were taken in a laboratory classroom setting during which children completed independent math and reading worksheets . Measures of social behavior were taken in structured , small-group board game setting s and unstructured recess setting s. Measures included behavior frequency counts , academic problems completed and accuracy , independent observations , teacher and counselor ratings , and individualized behavioral target goals . Reports of adverse events , sleep quality , and appetite were collected . RESULTS On virtually all measures in all setting s , both drug conditions were significantly different from placebo , and the 2 drugs were not different from each other . In children 's regular school setting s , both medications improved behavior as measured by teacher ratings and individualized target behaviors ( the DRC ) ; these effects were seen into the evening as measured by parent ratings . In the laboratory setting , effects of Concerta were equivalent to tid MPH and lasted at least through 12 hours after dosing . Concerta was significantly superior to tid MPH on 2 parent rating scores , and when asked , more parents preferred Concerta than preferred tid IR MPH or placebo . Side effects on children 's sleep and appetite were similar for the 2 preparations . In the lab setting , both medications improved productivity and accuracy on arithmetic seatwork assignments , disruptive and on-task behavior , and classroom rule following . Both medications improved children 's rule following and negative behavior in small group board games , as well as in unstructured recess setting s. Individual target behaviors also showed significant improvement with medication across domains in the laboratory setting . Children 's behavior across setting s deteriorated across the laboratory day , and the primary effect of medication was to prevent this deterioration as the day wore on . Results support the use of background behavioral treatment in clinical trials of stimulant medication , and illustrate the utility of a measure of individualized daily target goals ( ie , the DRC ) as an objective measure of medication response in both the laboratory and natural school setting s. CONCLUSION This investigation clearly supports the efficacy of the Concerta long-acting formulation of MPH for parents who desire to have medication benefits for their child throughout the day and early evening . ( ABSTRACT TRUNCATED", "Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind , placebo-controlled , crossover evaluation of the efficacy of st and ard methylpheni date twice a day and comparable doses every morning of a sustained-release preparation of methylpheni date ( SR-20 Ritalin ) , a sustained-release form of dextroamphetamine ( Dexedrine Spansule ) , and pemoline . The children were participating in a summer treatment program in which they engaged in recreational and classroom activities . Dependent measures include evaluations of social behavior during group recreational activities , classroom performance , and performance on a continuous performance task . Results revealed generally equivalent and beneficial effects of all four medications . Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication . The continuous performance task results showed that all four medications had an effect within 2 hours of ingestion , and the effects lasted for 9 hours . The implication s of these results for the use of long-acting stimulant medication in children with attention deficit-hyperactivity disorder are discussed", "OBJECTIVE The objective of this study was to evaluate differences in the pharmacodynamic ( PD ) profile of 2 second-generation extended-release ( ER ) formulations of methylpheni date ( MPH ) : Meta date CD ( MCD ; methylpheni date HCl , US Pharmacopeia ) extended-release capsules , CII , and Concerta ( CON ; methylpheni date HCl ) extended-release tablets , CII . Little empirical information exists to help the clinician compare the PD effects of the available ER formulations on attention and behavior . Previous studies have shown that the near-equal doses of MCD and CON provide equivalent , total exposure to MPH as measured by area under the plasma concentration time curve , yet their pharmacokinetic ( PK ) plasma concentration versus time profiles are different . We previously offered a theoretical PK/PD account of the similarities and differences among available ER formulations based on the hypothesis that all formulations produce effects related to MPH delivered by 2 processes : 1 ) an initial bolus dose of immediate-release ( IR ) MPH that is expected to achieve peak plasma concentration in the early morning and have rapid onset of efficacy within 2 hours of dosing , which for the MCD capsule is delivered by 30 % of the total daily dose as uncoated beads and for the CON tablet is delivered by an overcoat of 22 % of the total daily dose ; and 2 ) an extended , controlled delivery of ER MPH that is expected to achieve peak plasma concentrations in the afternoon to maintain efficacy for a programmed period of time after the peak of the initial bolus , which for the MCD capsule is delivered by polymer-coated beads and for the CON tablet by an osmotic-release oral system . According to this PK/PD model , clinical superiority is expected at any point in time for the formulation with the highest MPH plasma concentration . METHODS This was a multisite , double-blind , double-dummy , 3-way crossover study of 2 active treatments ( MCD and CON ) and placebo ( PLA ) . Children with confirmed diagnoses of attention-deficit/hyperactivity disorder were stratified to receive bioequivalent doses of MCD and CON that were considered to be low ( 20 mg of MCD and 18 mg of CON ) , medium ( 40 mg of MCD and 36 mg of CON ) , or high ( 60 mg of MCD and 54 mg of CON ) , and in a r and omized order each of the study treatments was administered once daily in the morning for 1 week . On the seventh day of each treatment week , children attended a laboratory school , where surrogate measures of response were obtained by using teacher ratings of attention and deportment and a record of permanent product of performance on a 10-minute math test at each of the 7 classroom sessions spread across the day at 1.5-hour intervals . Safety was assessed by patient reports of adverse events , parent ratings on a stimulant side-effects scale , and measurement of vital signs . RESULTS The analyses of variance revealed large , statistically significant main effects for the within-subject factor of treatment for all 3 outcome measures ( deportment , attention , and permanent product ) . The interactions of treatment x session were also highly significant for all 3 outcome measures . Inspection of the PD profiles for the treatment x session interactions suggested 4 patterns of efficacy across the day : 1 ) PLA > MCD approximately CON ( PLA superiority ) immediately after dosing ; 2 ) MCD > CON > PLA during the morning ( MCD superiority ) ; 3 ) MCD approximately CON > PLA during the afternoon ( PD equivalence of MCD and CON ) ; and 4 ) CON > MCD approximately PLA in the early evening ( CON superiority ) . The effect of site was significant , because some study centers had low and some high scores for behavior in the lab classroom , but both the low- and high-scoring sites showed similar PD patterns across the day . The interaction of dose x treatment was not significant , indicating that the pattern of treatment effects was consistent across each dose level . There were no statistically significant overall differences among the 3 treatments for the frequency of treatment-emergent adverse events , ratings of side effects , or vital signs . Two additional PK/PD questions were addressed : 1 . The a priori hypothesis called for a comparison of the average of sessions ( removing session as a factor ) during a time period that corresponds to the length of a typical school day ( from 1.5 through 7.5 hours after dosing ) . For the planned contrast of the 2 treatment conditions ( MCD versus CON ) , the difference was significant , confirming the a priori hypothesis of superiority of near-equal daily doses of MCD over CON for this predefined postdosing period . 2 . In the design of the study , the dose factor represented the total daily dose , consisting of 2 components : the initial bolus doses of IR MPH , which differ for the near-equal total daily doses of MCD and CON , and the reservoir doses of ER MPH , which were the same for the 2 formulations . To evaluate the moderating effects of the bolus component of dose on outcome , average effect size ( ES ) was calculated for the efficacy outcomes at the time of expected peak PK concentration times of the initial bolus component for each formulation at the 3 dose levels . The correlation ( r ) of ES with IR MPH bolus dose was significant for each of the 3 outcome measures ( r approximately .9 ) , indicating that the magnitude of effects in the early morning may be attributed to the dose administered by the IR MPH bolus of each formulation . For the 2 dose conditions with equal 12-mg IR MPH boluses ( MCD 40 and CON 54 ) , the ESs were large and indistinguishable ( eg , deportment ES approximately 0.75 for both ) . CONCLUSIONS Once-daily doses of MCD and CON produced statistically significantly different PD effects on surrogate measures of behavior and performance among children with attention-deficit/hyperactivity disorder in the laboratory school setting . As predicted by the PK/PD model , superiority at any point in time was achieved by the formulation with the highest expected plasma MPH concentration", "Objective . To assess effects of OROS methylpheni date on cognitive and academic tasks in 9 to 12 year olds with attention-deficit/hyperactivity disorder ( ADHD ) . Methods . A double-blind , within-subject , crossover design was used to compare OROS methylpheni date with placebo in a laboratory classroom setting on several cognitive and academic tasks for 68 children who met r and omization criteria . Results . Performance on the following measures was significantly better when children received individually optimized OROS methylpheni date than placebo : math fluency and accuracy measured by the Permanent Product Math Test , ADHD symptoms observed in the laboratory setting , computerized indices of attention and impulsivity as measured by the Test of Variables of Attention ( TOVA ) , and visual — spatial working memory ( Finger Windows Backwards ) . Study medication was well tolerated ; adverse events were generally consistent with previous reports . Conclusions . OROS methylpheni date improves performance on measures of attention and vigilance , behavior , and working memory in a laboratory school setting in 9 to 12 year olds with ADHD", "BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement ) combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes", "In children with attention deficit hyperactivity disorder ( ADHD ) , the effects of methylpheni date were investigated in a pharmacodynamic comparison of placebo and the st and ard b.i.d . administration of methylpheni date . In each of these conditions , teachers completed ratings in classroom setting s at times chosen to coincide with expected \" peaks \" and \" troughs \" of serum concentrations in the b.i.d . condition . Analyses of variance ( ANOVAs ) revealed the expected differences between the two conditions in the laboratory classroom setting using st and ard rating scales ( Conners and the IOWA Conners ) and a new rating scale ( the SKAMP ) , which specifically measures the classroom manifestation of ADHD . The psychometric properties of the SKAMP were evaluated by calculating test-retest reliability and by calculating correlations with the st and ard rating scales to establish concurrent validity", "The study examined the sustained effects of methylpheni date on reading performance in a sample of 42 boys , ages 8 to 11 , with attention deficit-hyperactivity disorder ( ADHD ) . Two subgroups were formed based on the presence or absence of co-occurring conduct disorders . Subjects were selected on the basis of their positive response to methylpheni date as determined in a series of original medication trials ( Forness , Cantwell , Swanson , Hanna , & Youpa , 1991 ) . For the purpose of this study , subjects were placed on their optimal dose of medication for a 6-week period and then tested on measures of oral reading and reading comprehension equivalent to those used in the original trials , retested after a week without medication ( placebo ) , then tested again the following week after return to medication . Only the subgroup with conduct disorders responded , and this response was limited to reading comprehension improvement in only those subjects who also demonstrated improvement in oral reading on original trials . No response differences were found between subjects with or without learning disabilities", "To examine the social effects of methylpheni date , groups of 15 attention-deficit disordered boys with ( ADD ) and 15 ADD boys without conduct problems ( ADD/CP ) were paired with normal peers . ADD and ADD/CP children showed a different pattern of responses to methylpheni date . While on task behavior in ADD/CP dyads increased at 0.15 mg/kg doses , increases in ADD dyads were not observed until doses reached 0.50 mg/kg . Although controlling interaction in ADD children decreased at 0.15 mg/kg , the controlling behavior of ADD/CP children did not decline at either dose . Peers of both ADD and ADD/CP children showed reciprocal declines in controlling behavior . In both free play and cooperative task situations , 0.15 mg/kg increased social interaction in ADD boys and decreased social interaction in ADD/CP boys", "BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) often , but not always , persists into adulthood . Investigations of the associations between clinical and biological markers of persistence can shed light on causal pathways . It has been proposed that compensatory improvements in executive neuropsychological functioning are associated with clinical improvements . This is the first study to test this hypothesis prospect ively . METHOD The clinical and neuropsychological functioning of 17 boys with ADHD ( mean age 10.45 years at time 1 ; 14.65 years at time 2 ) and 17 typically developing ( TYP ) boys ( mean age 10.39 years at time 1 ; 14.47 years at time 2 ) was tested on two occasions , 4 years apart . This was done using a battery of st and ardized neuropsychological tests that included tasks with high and low executive dem and s. RESULTS Clinical improvements were observed over time . Neuropsychological performance improvements were also evident , with ADHD boys developing with a similar pattern to TYP boys , but with a developmental lag . Whilst there was an association between reduced symptoms and superior performance at retest for one task with a high executive dem and ( spatial working memory ) , this was not seen with two further high executive dem and tasks [ Stockings of Cambridge and intra-dimensional extra-dimensional ( ID/ED ) set shifting ] . Also , there was no association between change in executive functioning and change in symptoms . Baseline performance on the ID/ED set-shifting task predicted better clinical outcome . Only change in performance on the low executive dem and delayed matching-to- sample task predicted better clinical outcome . CONCLUSIONS These data highlight the importance of longitudinal measurements of cognition , symptoms and treatment response over time in children and adolescents with ADHD", "Controversy surrounding stimulant medication , particularly its effects on reading performance , continues to obscure the issue of the use of this drug in classroom situations . The present study emphasized careful differential diagnosis , double-blind and placebo approaches , and curriculum-based dependent measures to address these concerns . Methylpheni date was administered to two groups of boys , ages 8 through 11 . The two groups included 27 subjects meeting criteria for attention deficit-hyperactivity disorder but not conduct disorder , known as hyperactive disorder ( HD ) , and 28 subjects meeting criteria for both diagnostic categories , known as hyperactive-aggressive ( HA ) . Only four subjects in each group met a discrepancy criterion for learning disabilities ( LD ) . Methylpheni date was administered to both groups at three levels of dosage , along with baseline and placebo conditions . Dependent measures involved both reading recognition and reading comprehension , equivalent across all conditions . No significant results were found for the group with HD in either reading recognition or comprehension , due largely to unusual placebo reactions . Results were generally in the direction predicted for the group with HA , but only significantly so in reading comprehension , and no dose effect was found on this variable . Implication s for reading as a dependent measure of medication effects are discussed", "Abstract Background Given the dosing limitations of methylpheni date short – acting preparations in treating ADHD , galenics with longer release of the substance were developed mainly to avoid drug intake during school hours . Objectives This investigation was conducted to assess the efficacy and the duration of action of a new extended-release formulation of methylpheni date ( Medikinet ® retard ) as a once – daily treatment for children with attention – deficit hyperactivity disorder ( ADHD ) . Method This was a r and omized , double – blind , crossover multicentre study with three treatment conditions : once – daily extended – release methylpheni date , twice – daily immediate – release methylpheni date and placebo given to 79 children ( 8–14 years old ) with ADHD . Daily assessment s in an analogue classroom setting included blind ratings of attention and deportment and a performance measure ( math test ) obtained 5 times over an 8–hour period . Secondary measures included an ADHD rating scale , based on DSMIV/ ICD–10 separately rated for the morning and the afternoon . Results Both active treatment conditions displayed significant time course effects and were superior to placebo in improving all efficacy measures . Once a day extended – release methylpheni date was not different from the same dose of twice daily immediate – release methylpheni date . Conclusions These data provide support for the benefit of this novel , once-daily methylpheni date preparation in the treatment of ADHD . The longer duration of action of Medikinet Retard has the potential to simplify psychostimulant treatment , thus reducing dose diversion and eliminating the need for in – school administration", "The investigation aim ed to delineate the immediate effect of methylpheni date on decoding in the comorbid condition of attention-deficit/hyperactivity disorder and reading disorder . Boys with attention-deficit/hyperactivity and reading disorders ( n = 25 ) between the ages of 7.9 and 11.7 years , with at least average intelligence and verbal processing abilities participated in a double-blind , acute , r and omized , placebo-controlled crossover trial with a single dose of methylpheni date 0.3 to 0.4 mg/kg with weekly intervals between testing sessions . The test battery included tasks of attention/control functions and reading domain functions . Paired comparisons and first trial group comparison comparing performance under placebo and under methylpheni date were used . Methylpheni date selectively improved strategy /set shift ( P = 0.004 ) and facilitated improvement both in rapid naming ( P = 0.043 ) and word/nonword accuracy ( P = 0.028/P = 0.035 ) . These findings lend support to a possible influence of methylpheni date on cognitive attention functions related to reading skills in the comorbid group", "Two studies were conducted to investigate the relative effects of sustained release methylpheni date ( Ritalin [ SR-20 ] ) and st and ard methylpheni date ( Ritalin , 10 mg , administered twice daily ) . In the first study , 13 boys with attention deficit disorder participating in a summer treatment program went through a double-blind , within-subject trial of each form of methylpheni date and placebo . Measures of social and cognitive behavior were gathered in classroom and play setting s. Although group analyses of the data showed that both drugs were effective and there were few differences between them , st and ard methylpheni date was superior to SR-20 on several important measures of disruptive behavior . Furthermore , analyses of individual responsivity showed clearly that most boys responded more positively to st and ard methylpheni date than to SR-20 . The second study involved a partially overlapping group of nine boys with attention deficit disorder participating in the same summer treatment program . Also double-blind , within-subject , and placebo controlled , this study tracked the time courses of the two forms of methylpheni date . Both were shown to have similar time courses on the Abbreviated Conners Rating Scale and other measures , but SR-20 had a slower onset than did the st and ard drug form on a continuous performance task . Effects of SR-20 were still evident eight hours after ingestion", "Sixteen children meeting diagnostic criteria for Attention Deficit Disorder with Hyperactivity ( ADD-H ) were tested on methylpheni date ( 0.3 mg/kg ) and placebo on cognitive , learning , academic and behavioral measures in a double-blind study . Assessment s were carried out in the laboratory and in the children 's regular classrooms . Results indicate methylpheni date -induced improvements on a majority of the measures . Drug-induced changes reflected increased output , accuracy and efficiency and improved learning acquisition . There was also evidence of increased effort and self-correcting behaviours . It is argued that review ers have underestimated the potential of stimulants to improve the performance of ADD-H children on academic , learning and cognitive tasks", "OBJECTIVE To examine the pharmacokinetics ( PKs ) and pharmacodynamics ( PDs ) of OROS methylpheni date ( OROS MPH ) dosed once daily ( QD ) versus an early st and ard regimen ( immediate-release [ IR ] MPH dosed three times daily [ TID ] ) under various breakfast conditions . METHODS This single-center , double-blind , double-dummy , r and omized , crossover study of OROS MPH ( NCT00269815 ) in children aged 6 to 12 years with attention-deficit/hyperactivity disorder evaluated the PKs and PDs of MPH given with different breakfast conditions : OROS MPH administered after a high-fat breakfast , after a normal breakfast , or after fasting and IR MPH administered after a normal breakfast or after fasting in the morning and at two subsequent time points during the day . To maximize information , patients were divided into two groups , each receiving three of the five treatments for 1 day in a three-period , r and omized , crossover design . Patients were assigned to 1 of 3 dosage levels ( OROS MPH 18 , 36 , and 54 mg QD , and an assumed equivalent regimen of IR MPH 5 , 10 , and 15 mg given TID ) based on their pre study established clinical dose of IR MPH . PD measurements included Combined-Attention and Deportment scores on a rating scale of school behavior ( the Swanson , Kotkin , Agler , M-Flynn , and Pelham ) , global assessment s of efficacy , and activity monitor levels during academic seatwork . Serial blood sample s for PK analysis were taken predose , and then every 60 to 90 minutes until 11.5 hours postdose . Vital signs were assessed predose , and then every 1.5 to 2.5 hours until 11.5 hours postdose . RESULTS Of the 32 patients enrolled , 31 completed the study . The PK profiles for MPH after OROS MPH administration were similar under all conditions ( with normal , high-fat breakfast , or fasting ) . No bioequivalence tests of OROS MPH and IR MPH under various breakfast conditions were done because there were so few patients in each dose level of treatment . The two IR MPH conditions ( after normal breakfast and fasting ) were not compared . The drug-to-metabolite ratios ( area under the curve ) for all OROS MPH and IR MPH treatments were similar . OROS MPH and IR MPH provided a similar therapeutic effect , irrespective of breakfast conditions , as demonstrated by the Swanson , Kotkin , Agler , M-Flynn , and Pelham Attention and Deportment measures and global assessment s. No serious adverse events , no deaths , and no clinical ly significant changes in vital signs were reported , except for one patient who was discontinued early because of repeated systolic blood pressure elevations on study day 1 . CONCLUSIONS The results of this study demonstrate that in children with attention-deficit/hyperactivity disorder , administering OROS MPH with or without food produces similar PK and PD profiles", "Objective : To explore treatment response to Osmotic Release Oral System ® ( OROS ) methylpheni date in children with ADHD with and without comorbid learning disability ( LD ) . Method : Data were analyzed from two 6-week , double-blind , r and omized , placebo-controlled , crossover studies evaluating individually determined doses of OROS methylpheni date versus placebo in 135 children ( ages 9 to 12 years ) with ADHD with or without an LD in reading , math , or both . The sample was demographically diverse , with 31 % females and more than 40 % minority , predominantly African American and Hispanic . On two laboratory school days , participants received either OROS methylpheni date or placebo and were given a battery of cognitive and behavioral tests . Results : Treatment with OROS methylpheni date led to improvement in ADHD Rating Scale scores for participants with or without comorbid LD . Both groups performed better during treatment with OROS methylpheni date than placebo on measures of cognitive skills ( i.e. , Test of Variables of Attention , Finger Windows Backwards ) , academically related tasks ( i.e. , Dynamic Indicators of Basic Early Literacy Skills , Test of H and writing Skills – Revised , Permanent Product Math Test ) , and observed classroom behavior ( i.e. , Swanson , Kotkin , Alger , M-Flynn , and Pelham Scale ) . Conclusion : In children with ADHD with or without comorbid LD , behavior and performance improved during treatment with OROS methylpheni date", "The short-term , dose-response effects of methylpheni date hydrochloride were evaluated on academic and social classroom measures in 29 children with attention deficit disorder . In a double-blind , cross-over design with order r and omized , children received a placebo for two weeks and three doses of methylpheni date hydrochloride ( 0.15 mg/kg , 0.3 mg/kg , and 0.6 mg/kg ) for one week each . Dependent measures included the output and accuracy of performance in grade -appropriate reading comprehension workbooks and arithmetic problems , spelling word acquisition , and observations of disruptive and on-task behavior . Beneficial drug effects and linear dose-response curves on all dependent measures were found . The results suggest that beneficial methylpheni date effects on classroom behavior may be accompanied by enhanced academic achievement in some hyperactive children", "The effects of 0.3 mg/kg methylpheni date were compared for 12 ADD boys and 12 ADD girls participating in a summer treatment program for children with behavior and /or learning problems . Previous investigations have suggested that ADD girls may differ from ADD boys in some important respects . No information exists regarding whether the effects of the most common treatment for these children , methylpheni date , has comparable effects on boys and girls . The boys and girls were matched for age and IQ . The results revealed equivalent and beneficial effects of methylpheni date for both boys and girls . Methylpheni date therefore would appear to be as useful a treatment for ADD girls as for ADD boys", "Objective : The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylpheni date ( OROS ® MPH ) HCl ( Concerta ® , Raritan , NJ ) CII in children with ADHD . Method : Data were combined from two double-blind , r and omized , placebo-controlled , cross-over , analog classroom studies in children ( 9 - 12 years ) with ADHD . Participants received an individualized dose of placebo or OROS ® MPH on two laboratory school days . Permanent Product Math Test and Swanson , Kotkin , Agler , M-Flynn , and Pelham scores were evaluated 0.5 hr before dosing and 1 , 2 , 4 , 10 , 11 , and 12.5 hr post dose . Analysis used a repeated- measures mixed model . Results : Treatment effects were present at all postdose assessment points ( p n = 139 ) . Adverse events were similar to previous reports for OROS ® MPH . Conclusion : A robust treatment effect occurred with OROS ® MPH ; onset was at 1 hr and persisted for at least 12.5 hr after dosing", "ABSTRACT Clinical trials with a treatment duration of at least 3 months were review ed to determine the effect of psychostimulants on the core symptoms of attention-deficit hyperactivity disorder ( ADHD ) and on its commonly associated features . Eighteen studies were identified : 17 were studies of methylpheni date , 1 was a study of dextroamphetamine , and none involved pemoline or slow-release stimulants . Eleven of these studies were r and omized controlled trials , whereas seven employed quasi-experimental design s without r and omization . The results of r and omized controlled trials showed that psychostimulants provided greater benefit than did the nonr and omized trials , suggesting that the efficacy of extended treatment may have been underestimated because more seriously disturbed children were assigned to medication treatment than to control treatments in nonr and omized trials . Evidence from the more definitive r and omized controlled trials indicates that stimulants are more effective in ameliorating the core behavioral symptoms of ADHD ( restlessness , inattentiveness , impulsiveness ) than placebos , nonpharmacological therapies , or no treatment-at least in 3 - 7-month trials . During extended psychostimulant treatment , few children become symptom-free , clinical effects may diminish with time , and improvement dissipates rapidly upon discontinuation of medication . There is minimal evidence that extended stimulant treatment improves cognitive deficits or associated problems such as conduct disturbance , low self-esteem , poor peer relationships , or academic underachievement . The belief that stimulants do not improve the long-term prognosis of children with ADHD may be based on weakly design ed studies that focus on associated rather than core symptoms . A failure to assign patients of similar clinical severity to different treatment conditions may also have contributed to obscuring the efficacy of extended psychostimulant treatments" ]

[ "A population -based cohort study was done to estimate the incidence of different types of injuries and to evaluate certain risk factors in an urban slum ; 4333 slum dwellers in Madras city in India were r and omly selected by cluster sampling , of whom 1.7 per cent were lost during the 12 months of follow up . The cumulative injury incidence for 12 months for all injuries was 127 per 1000 persons ( 95 per cent confidence interval 117 - 137 ) ; for males 137 per 1000 and for females 118 per 1000 . Incidence of unintentional injury was 121 per 1000 persons . The incidence for road traffic injury was 16 per 1000 persons , for household injuries 57 per 1000 persons and for injury at place of work 19 per 1000 persons . The relative risk of males to females for traffic injuries was 3.04 and for household injuries was 0.39 . The relative risk of traffic injuries among adult males who reported daily alcohol consumption was 2.26 . The incidence of injury is high in an urban slum and it is a priority health problem . This study has identified groups of people who are at high risk for injuries and who may need specific protective measures", "This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer", "It is desirable that young women with primary ovarian failure achieve normal peak bone mass to reduce the subsequent risk of osteoporosis , and that there are management strategies to replace bone that is already lost . While estrogen ( E2 ) is generally considered to prevent bone loss by suppressing bone resorption , it is now recognized that estrogen also exerts an anabolic effect on the human skeleton . In this study , we tested whether estrogen could increase bone mass in women with primary ovarian failure . We studied the mechanism underlying this by analyzing biochemical markers of bone turnover and iliac crest biopsy specimens obtained before and 3 years after E2 replacement . Twenty-one women with Turner 's syndrome , aged 20 - 40 years , were studied . The T scores of bone mineral density at lumbar spine and proximal femur at baseline were -1.4 and -1.1 , respectively . Hormone replacement was given as subcutaneous E2 implants ( 50 mg every 6 months ) with oral medroxy progesterone . Serum E2 levels increased incrementally from 87.5 pM at baseline to 323 , 506 , 647 , and 713 pM after 6 months and 1 , 2 , and 3 years of hormone replacement therapy ( HRT ) , respectively . The bone mineral density at the lumbar spine and proximal femur increased after 3 years to T scores of -0.2 and -0.4 , respectively . The cancellous bone volume increased significantly from 13.4 % to 18.8 % . There was a decrease in activation frequency , but the active formation period was increased by HRT . There was a significant increase in the wall thickness from 33.4 microm at baseline to 40.9 microm after 3 years of HRT , reflecting an increase in bone formed at individual remodeling units . Although there was an early increase in biochemical markers of bone formation , these declined thereafter . Our results show that estrogen is capable of exerting an anabolic effect in the skeleton of young women with Turner 's syndrome and low bone mass", "The aim of the present study was to examine the impact of sequential change in the route of estrogen administration on body composition and insulin resistance in patients with Turner syndrome ( TS ) using cyclical hormone replacement therapy ( HRT ) with conjugated equine estrogens ( CEE ) plus medroxyprogesterone acetate ( MPA ) . We carried out a self-controlled study of nine non-obese patients with TS , with an average age of 23 ± 4.9 years . Body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , fasting glycemia , insulin tolerance ( glucose disappearance constant during an insulin tolerance test , kITT ) and body composition ( dual-energy X-ray absorptiometry ) were studied after 1 year 's use of CEE plus MPA and repeated after 1 year 's use of 17β-estradiol gel with the same schedule of MPA administration . We did not observe any difference between the oral and percutaneous HRT with regard to BMI , WHR and insulin tolerance ( kITT : 4.9 ± 1.5 vs. 5.3 ± 1.5%/min , p = 0.8 ) . During administration of the 17β-estradiol gel a tendency to increased total lean mass ( p = 0.054 ) was observed . We conclude that sequential change in the route of estrogen administration in TS patients using cyclical HRT with CEE and MPA does not affect insulin resistance , although use of percutaneous 17β-estradiol gel seems to exert favorable changes in body composition ", "Background There are limited long-term r and omized controlled trials of growth hormone ( GH ) supplementation to adult height and few published reports of the health-related quality of life ( HRQOL ) following treatment . The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome ( TS ) yielded data to examine whether GH supplementation result ed in a higher HRQOL ( either due to taller stature or from the knowledge that active treatment and not placebo had been received ) or alternatively a lower HRQOL ( due to medicalization from years of injections ) . Methods The original trial r and omized 154 Canadian girls with TS aged 7 - 13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections ; estrogen prescription for induction of puberty was st and ardized . Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up . The instrument used to study HRQOL was the SF-36 , summarized into physical and mental component scales ( PCS and MCS ) ; higher scores indicate better HRQOL . Results Thirty-four of the 48 eligible participants ( 71 % ) consented to participate ; data were missing for one patient . Both groups ( GH and no treatment ) had normal HRQOL at this post-treatment assessment . The GH group had a ( mean ± SD ) PCS score of 56 ± 5 ; the untreated group 58 ± 4 ; mean score for 16 - 24 year old females in the general population 53.5 ± 6.9 . The GH group had a mean MCS score of 52 ± 6 ; the untreated group 49 ± 13 ; mean score for 16 - 24 year old females in the general population 49.6 ± 9.8 . Secondary analyses showed no relationship between HRQOL and height . Conclusions We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term r and omized controlled trial , confirming larger observational studies . We suggest that it remains ethically acceptable as well as necessary to maintain a long-term untreated control group to estimate the effects of pharmacological agents to manipulate adult height . Young adult women with TS have normal HRQOL suggesting that they adjust well to their challenges in life . Trial Registration Clinical Trials.gov Identifier NCT00191113", "OBJECTIVE To determine whether young women with Turner 's syndrome who had normal bone mineral density ( BMD ) before the induction of puberty maintain normal BMD in young adulthood . DESIGN Controlled clinical study . SETTING A private hospital clinical research setting . PATIENTS Young women with Turner 's syndrome in Tanner stage V of puberty with previously normal BMD . INTERVENTIONS Oral conjugated estrogens and progesterone acetate were administered continuously for a mean ( + /-SD ) of 4.1+/-1.0 years . Bone mineral densities and blood sample s were evaluated . MAIN OUTCOME MEASURE(S ) The BMD of the lumbar spine and the femoral neck was determined during young adulthood . The change in BMD over the previous 6 years also was evaluated . Serum concentrations of the carboxy-terminal propeptide of type 1 collagen and of the carboxy-terminal cross-linked telopeptide of type 1 collagen were measured . RESULT ( S ) The BMD of the lumbar spine was reduced significantly in our patients . There was no change in the BMD of the femoral neck or lumbar spine over a period of 6.1 years . Concentrations of the carboxy-terminal propeptide of type 1 collagen were decreased , whereas concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen were increased . CONCLUSION ( S ) Young women with Turner 's syndrome do not attain normal peak bone mass even when estrogen replacement therapy is begun in adolescence . Their low BMD seems to be due to decreased bone formation and increased bone resorption", "Background Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects . Currently , health care providers have varying practice s without evidence -based st and ards , thus investigating potential differences between oral and transdermal preparations is essential . The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen ( OCEE ) , oral 17β estradiol ( OBE ) , or transdermal 17β estradiol ( TBE ) on biochemical profiles and feminization in girls with ovarian failure . Study design 20 prepubertal adolescent females with ovarian failure , ages 12–18 years , were r and omized to OCEE ( n = 8) , OBE ( n = 7 ) , or TBE ( n = 5 ) for 24 months . Estrogen replacement was initiated at a low dose ( 0.15 mg OCEE , 0.25 mg OBE , or 0.0125 mg TBE ) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE , 1 mg/d OBE , or 0.05 mg/d TBE . At 18 months , micronized progesterone was added to induce menstrual cycles . Biochemical markers including sex hormones , inflammatory markers , liver enzymes , coagulation factors , and lipids were obtained at baseline and 6 month intervals . Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance ( ANOVA ) . The effect of progesterone on biochemical markers was evaluated with the paired t-test . Results Mean ( ±SE ) estradiol levels at maximum estrogen dose ( 18 months ) were higher in the TBE group ( 53 ± 19 pg/mL ) compared to OCEE ( 14 ± 5 pg/mL ) and OBE ( 12 ± 5 pg/mL ) ( p ≤ 0.01 ) . The TBE and OBE groups had more effective feminization ( 100 % Tanner 3 breast stage at 18 months ) . There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone . Conclusions Treatment with transdermal 17β estradiol result ed in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients . OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls , but larger prospect i ve r and omized trials are required . Trial registration Clinical Trials Identifier : NCT01023178", "Eight girls with Turner 's syndrome were given low dose oral ethinyl estradiol or transdermal 17 beta-estradiol in order to compare the effect of the route of administration on selected markers of hepatic metabolism , and various hormonal concentrations . Oral estrogen was given at a dose of 100 ng/kg/day and transdermal estrogen via adhesive skin patch at 0.0125 mg/kg/day . The subjects received one form of estradiol for one month , and after a one month washout period , received the other form . Both oral and transdermal estradiol caused a significant decrease in FSH while only transdermal result ed in a significant decrease in LH . Oral estradiol , though not transdermal estradiol , increased serum high density lipoprotein , thyroxine binding protein and growth hormone binding protein . Urinary growth hormone excretion increased after both forms of therapy , while insulin-like growth factor-I and insulin-like growth factor binding protein-3 remained unchanged . Thus , in girls with Turner 's syndrome , estrogen replacement by the transdermal route may have less deleterious effect on hepatic metabolism than oral estrogen", "CONTEXT Women with Turner syndrome ( TS ) have reduced levels of and rogens due to ovarian failure . HYPOTHESES Morbidity associated with TS , such as bone fragility , metabolic changes , obesity , neurocognitive profile , and sexual problems may partly relate to and rogen insufficiency and improve on and rogen replacement therapy ( ART ) . OBJECTIVES The objective of the study was to determine the effect of and rogens on morbidity in TS . DESIGN Fourteen TS women ( aged 17 - 27 yr ) participated in a r and omized , double-blind , placebo-controlled crossover pilot . The study was conducted in a hospital outpatient clinic between December 2001 and July 2004 . INTERVENTION TS patients were on estrogen/progestin replacement therapy . Subjects received oral 1.5 mg methyl testosterone ( ART ) or placebo for 1 yr and the alternative for another year . MAIN OUTCOME MEASURES The study compared body composition as a primary outcome , and physiology , biochemistry , visceral fat , cognition , and quality of life ( QOL ) as secondary outcomes . RESULTS ART as compared with placebo reduced total cholesterol , triglycerides , and high-density lipoprotein cholesterol . It improved bone mineral density , increased lean body mass , and decreased fat mass . ART improved attention , reaction time , and verbal memory and had no effect on executive functions and spatial cognition . Patients reported improved QOL , including general health , coping with stress , and sexual desire . CONCLUSIONS And rogen insufficiency plays a role in TS-impaired body composition , neurocognition , and QOL , and these aspects improve with ART , which was safe and effective when given for 1 yr", " OBJECTIVE Hormone replacement therapy ( HRT ) is prescribed to most patients with Turner syndrome ( TS ) although its use in adult TS patients has not been scientifically evaluated . The present study was performed to compare the short‐term effects in adult women with Turner syndrome of low‐dose oral conjugated oestrogen ( 0·625 mg , CE ) with relatively high dose ethinyl oestradiol ( 30 µg , EE2 ) ; both combined with an oral progestin", "Girls with Turner syndrome are mainly characterized by growth retardation and gonadal insufficiency . In order to evaluate the effect of growth hormone ( GH ) and /or low dose 17 beta-oestradiol ( E2 ) on growth and pubertal development , 39 Turner girls with a chronological age ( CA ) of 7.6 - 18.1 years were divided into three groups depending on pretreatment bone age ( BA ) . They were treated with either GH 0.1 IE/kg per day ( n = 13 , BA 7.1 - 10.2 ) , peroral E2 0.01 mg/kg per day ( n = 8 , BA 8.5 - 12.7 ) or both ( n = 18 , BA 10.5 - 15.3 ) . In the 2nd year the E2 group also received GH , while the E2 dose was reduced 30 % . In the 1st year height velocity ( HV ) expressed as st and ard deviation scores ( SDS ) increased in all groups ( mean ) : from -0.4 to 3.3 ( P GH group , -0.5 to 2.7 ( P E2 group , and -0.8 to 4.6 ( P GH+E2 group . A possible synergistic effect from combination therapy was seen , as HV increase was higher in group 3 than groups 1 and 2 ( P HV was unchanged in groups 1 and 2 , while a clear decrease was seen in the GH+E2 group ( P BA progression in the E2 group was rapid ( 1.9 BA/CA year ) and higher than in the other groups ( P E2 group ( 0.7 BA/CA year , P = 0.07 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Dyslipidemia causes coronary heart disease in middle-aged and elderly adults , but the consequences of lipid exposure during young adulthood are unclear . OBJECTIVE To assess whether nonoptimal lipid levels during young adulthood cause atherosclerotic changes that persist into middle age . DESIGN Prospect i ve cohort study . SETTING 4 cities in the United States . PARTICIPANTS 3258 participants from the 5115 black and white men and women recruited at age 18 to 30 years in 1985 to 1986 for the CARDIA ( Coronary Artery Risk Development in Young Adults ) study . MEASUREMENTS Low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol , triglycerides , and coronary calcium . Time-averaged cumulative exposures to lipids between age 20 and 35 years were estimated by using repeated serum lipid measurements over 20 years in the CARDIA study ; these measurements were then related to coronary calcium scores assessed later in life ( 45 years [ SD , 4 ] ) . RESULTS 2824 participants ( 87 % ) had nonoptimal levels of LDL cholesterol ( > or=2.59 mmol/L [ > or=100 mg/dL ] ) , HDL cholesterol ( triglycerides ( > or=1.70 mmol/L [ > or=150 mg/dL ] ) during young adulthood . Coronary calcium prevalence 2 decades later was 8 % in participants who maintained optimal LDL levels ( LDL cholesterol levels of 4.14 mmol/L ( 160 mg/dL ) or greater ( P coronary calcium of 1.5 ( 95 % CI , 0.7 to 3.3 ) for LDL cholesterol levels of 1.81 to 2.56 mmol/L ( 70 to 99 mg/dL ) , 2.4 ( CI , 1.1 to 5.3 ) for levels of 2.59 to 3.34 mmol/L ( 100 to 129 mg/dL ) , 3.3 ( CI , 1.3 to 7.8 ) for levels of 3.37 to 4.12 mmol/L ( 130 to 159 mg/dL ) , and 5.6 ( CI , 2.0 to 16 ) for levels of 4.14 mmol/L ( 160 mg/dL ) or greater , compared with levels less than 1.81 mmol/L ( LDL and HDL cholesterol levels were independently associated with coronary calcium after participants who were receiving lipid-lowering medications or had clinical ly abnormal lipid levels were excluded . LIMITATION Coronary calcium , although a strong predictor of future coronary heart disease , is not a clinical outcome . CONCLUSION Nonoptimal levels of LDL and HDL cholesterol during young adulthood are independently associated with coronary atherosclerosis 2 decades later . PRIMARY FUNDING SOURCE National Heart , Lung , and Blood Institute", "Because the long-term effects of estrogen replacement in adolescents with ovarian failure and hypothalamic amenorrhea have not been previously studied , we conducted a 2-year study of 35 patients to determine factors contributing to baseline bone density measures ( bone density , bone mineral content , and bone width ) and the response to estrogen therapy . Estrogen-deficient patients were often profoundly osteopenic by single-photon absorptiometry of the radius and dual-photon absorptiometry of the spine , despite estrogen replacement . Variables that were significant predictors of better initial single-photon absorptiometry measurements included increased age , increased body mass index , spontaneous pubertal development , lack of radiation therapy , and lower serum osteocalcin . Patients treated with estrogen/progestin had stable cortical bone mineral content and bone density at the distal one-third of the radius , a slight improvement in bone density at the distal one-tenth of the radius , and an encouraging , but marginal , improvement in the z score ( st and ard deviation from the mean ) of bone mineral content at the distal onetenth . The z scores for cortical bone width and bone density decreased , suggesting a possible relative worsening over time . In untreated estrogen-deficient girls , bone mineral content and bone density decreased ( but not significantly ) ; the z score of cortical bone width showed a significant decrease . Using dual-photon absorptiometry , a history of radiation therapy was found to be a predictor of lower bone density compared with age-matched controls . Estrogen/ progestin therapy did not result in changes in serum levels of lipids and antithrombin HI , weight , or blood pressure . This study suggests that because most adolescent/young adult patients with estrogen deficiency may not achieve normal bone density with current therapy , earlier and more aggressive intervention may be necessary", "Lumbar spine bone mineral density ( BMD ) values were measured in women with Turner 's syndrome ( TS ) and the influence of primary ovarian failure as well as the age at the start of estroprogestins ( EP ) therapy were considered . EP treatment with 2 mg of estradiol ( E2 ) and BMD monitoring were started in 72 and finally continued for 5 years in 34 patients with TS , aged 12 - 38 years , previously not treated with growth hormone or anabolic steroids . The mean total BMD gain ( deltaBMD ) was 20 % and the most significant increase was observed after the first ( 7.5 % ) and the second ( 6.6 % ) year of the therapy . Before the start and during EP treatment E2 levels were evaluated : they increased from 9.2pg/ml to the values observed in the controls ( C ) but positive correlation with BMD was not observed . Analysis of TS patients in age brackets ( 25 years ) showed that only in the group that started EP treatment before the age of 15 every year significant deltaBMD was observed . The group that started EP therapy after the age of 20 did n't achieve significant deltaBMD . Patients wit TS had significantly higher levels of bone metabolism markers ( Ntx and BALP ) than the controls and in both groups negative correlation with age was found . On the basis of the results the conclusion was made that in hypoestrogenic women , not exclusively TS , the age when estrogen therapy is started may determine the effects in relation to bone mass . The administered E2 doses may also be important", "In a prospect i ve study of 156 female patients with Turner 's syndrome who had survived infancy and been followed up for an average of 17 years there were 15 deaths . The expected mortality was 3.6 . Sixteen of the patients had a congenital heart anomaly and five of the deaths occurred in this group . The 10 deaths in the remaining 140 were three times as many as expected . The reduction in life expectation was 12.5 years at age 1 year , 11 years at age 20 , and 10 years at age 40 . Deaths were due to a broad spectrum of diseases . In the sample as a whole there were eight deaths from diseases of the circulatory system . This number is significantly greater than expected , but four were due to congenital heart disease . When patients with congenital heart disease were omitted from the sample the mortality from circulatory disorders was not significantly increased . Within the category of circulatory disorders there were three deaths from dissection of the aorta , a number which is greatly in excess of the expected . Two of these patients had no previous evidence of heart disease" ]

[ "& NA ; A series of health surveys are conducted every sixth to seventh year in Denmark . In the most recent survey of 2000 , a national r and om sample ( > 16 years ) was drawn from the Danish Central Personal Register . Out of the original sample 12,333 ( 74 % ) were interviewed and of these 10,066 returned a completed question naire ( SF‐36 ) . The present study includes only those who both took part in the interview and the postal question naire . Cancer patients were excluded . Persons suffering from chronic pain ( PG ) were identified through the question ‘ Do you have chronic/long lasting pain lasting 6 months or more ’ ? An overall chronic pain prevalence of 19 % was found −16 % for men and 21 % for women . Prevalence of chronic pain increased with increasing age . Persons ≥67 years had 3.9 higher odds of suffering from chronic pain than persons in the age group 16–24 years . Compared with married persons , divorced or separated persons had 1.5 higher odds of chronic pain . Odds for chronic pain were 1.9 higher among those with an education of less than 10 years compared with individuals with an education of 13 years or more . During a 14‐day period reporters of chronic pain had an average of 0.8 days ( range 0–10 ) lost due to illness compared with an average of 0.4 days ( range 0–10 ) for the control group ( CG ) ( Odds Ratio ( OR ) ) 2.0 ) . Persons with a job which required high physical strain were more likely to report chronic pain compared with those with a sedentary job ( OR 2.2 ) . The odds of quitting one 's job because of ill health were seven times higher among people belonging to the PG . A strong association between chronic pain and poor self‐rated health was also demonstrated . The PG had twice as many contacts with various health professionals compared with the CG , and the health care system was , on average , utilised 25 % more ( overall contacts ) by the PG than by the general population . Among the persons in the PG , 33 % were not satisfied with the examinations carried out in connection with their pain condition and 40 % were not satisfied with the treatment offered . Nearly 130,000 adults , corresponding to 3 % of the Danish population , use opioids on a regular basis . Opioids are used by 12 % of the PG", "Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems", "Background and Objective : Psychological factors are assumed to predict persistent or recurrent musculoskeletal pain . The influence of psychological factors in patients with low-back pain ( LBP ) or shoulder pain was explored to study whether there is similarity regarding the factors that predict persisting pain and disability . Methods : Patients presenting in primary care with a new episode of shoulder pain or non-specific (sub)acute low back pain ( LBP ) were enrolled in a prospect i ve study . In both patient groups , pain catastrophising , distress , somatisation and fear-avoidance beliefs were measured at baseline . Primary outcome measures at 3 months were ( 1 ) persistent symptoms , and ( 2 ) Multivariate logistic regression analysis was used to study the associations between psychological factors and outcome . Results : A total of 587 patients with shoulder pain and 171 patients with LBP were enrolled in the study . In patients with shoulder pain , most associations of psychological factors with outcome were weak and not significant . Only in patients with longer symptom duration at baseline ( ⩾3 months ) were higher scores on catastrophising significantly associated with persistent symptoms ( p = 0.04 ) . In patients with LBP , psychological factors were more strongly associated with poor outcome , although most associations were not significant . Conclusion : Psychological factors , with the exception of fear-avoidance beliefs , are more strongly associated with persistent pain and disability in patients with LBP than in those with shoulder pain . This seems to indicate that in a primary care population the influence of psychological factors on outcome may vary across patients with different types of pain ", "A clinical prediction rule to identify patients most likely to respond to spinal manipulation has been published and widely cited but requires further testing for external validity . We performed a pre-planned secondary analysis of a r and omised controlled trial investigating the efficacy of spinal manipulative therapy in 239 patients presenting to general practice clinics for acute , non-specific , low back pain . Patients were r and omised to receive spinal manipulative therapy or placebo 2 to 3 times per week for up to 4 weeks . All patients received general practitioner care ( advice and paracetamol ) . Outcomes were pain and disability measured at 1 , 2 , 4 and 12 weeks . Status on the clinical prediction rule was measured at baseline . The clinical prediction rule performed no better than chance in identifying patients with acute , non-specific low back pain most likely to respond to spinal manipulative therapy ( pain P = 0.805 , disability P = 0.600 ) . At 1-week follow-up , the mean difference in effect of spinal manipulative therapy compared to placebo in patients who were rule positive rather than rule negative was 0.3 points less on a 10-point pain scale ( 95 % CI −0.8 to 1.4 ) . The clinical prediction rule proposed by Childs et al. did not generalise to patients presenting to primary care with acute low back pain who received a course of spinal manipulative therapy", "IMPORTANCE Many site-specific , multivariable risk models for predicting the outcome of musculoskeletal pain problems have been published . The overlapping content in these models suggests a common set of generic indicators suitable for use in primary care . OBJECTIVE To investigate whether a brief set of generic prognostic indicators can predict the outcome of musculoskeletal pain in older patients presenting to general practitioners . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve observational cohort study conducted from September 1 , 2006 , through March 31 , 2007 , of consecutive patients 50 years or older presenting with noninflammatory musculoskeletal pain to 1 of the 5 participating general practice s in the United Kingdom . MAIN OUTCOME MEASURES During consultation , the treating physician assessed and recorded 5 brief generic items ( duration of present pain episode , current pain intensity , pain interference with daily activities , presence of multiple-site pain , and ultrashort depression screen ) and recorded their overall prognostic judgment . The primary outcome was patient-rated improvement , which was measured 6 months after consultation and cross-vali date d with repeated measures up to 3 years . RESULTS A total of 194 ( 48.1 % ) of 403 participants were classified as having an unfavorable outcome at 6 months . Inclusion of 3 generic prognostic indicators ( duration of present pain episode , pain interference with daily activities , and presence of multiple-site pain ) in the prognostic model improved on reliance on physicians ' prognostic judgment alone ( C statistic = 0.72 vs 0.62 ; net reclassification index = 0.136 ; proportion correctly classified = 69 % ) . The improvement in prognostic accuracy was attributable to correcting physicians ' tendency toward overoptimistic expectations of outcome . CONCLUSIONS AND RELEVANCE Three easy-to-obtain pieces of information followed by systematic recording of the general practitioners ' prognostic judgment provide a simple generic assessment of prognosis at point of care in older persons presenting with musculoskeletal problems to primary care practice s in the United Kingdom . Such an assessment offers a common foundation for investigating the usefulness of prognostic stratification for guiding management in the consultation across a range of common painful conditions", "& NA ; Few studies have investigated whether prognostic indicators , which contribute to the transition from acute to chronic low back pain ( LBP ) , are also those which contribute to continuing persistence of chronic LBP . We compared the contribution of physical , psychological and social indicators to predicting disability after one year between consulters with LBP of less than 3 months duration and more than 3 months duration . Data from two large prospect i ve cohort studies of consecutive patients consulting with LBP in general practice s were merged , providing complete data for 258 cases with acute/subacute LBP and 668 cases with chronic LBP at 12 months follow‐up . There were significant differences between the two LBP groups in baseline characteristics and clinical course of disability , assessed by Rol and Morris Disability Question naire , during the year of follow‐up . Adjusted associations between potential prognostic indicators and disability at 12 months were carried out in the two LBP subgroups . The final multivariable regression models showed that being non‐employed , having widespread pain , a high level of Chronic Pain Grade , and catastrophising were the strongest prognostic indicators for disability at 12 months in both LBP groups . Fear of pain was significantly associated with disability in chronic LBP . Importantly , beyond baseline disability , the effect size of the other prognostic indicators for poor outcome was rather low . These findings must continue to challenge research ers to identify useful early predictors of outcome in persons with disabling back pain , as screening and targeted treatment approaches are dependent upon prognostic indicators with clinical significance", "Background Advice to remain active and normalisation of activity are commonly prescribed in the management of low back pain ( LBP ) . However , no research has assessed whether objective measurements of physical activity predict outcome and recovery in acute low back pain . Method The aims of this study were to assess the predictive relationship between activity and disability at 3 months in a sub-acute LBP population . This prospect i ve cohort study recruited 101 consenting patients with sub-acute LBP ( Rol and Morris Disability Question naire ( RMDQ ) , the Visual Analogue Scale , and resumption of full ‘ normal ’ activity question ( Y/N ) , at baseline and 3 months . Physical activity was measured for 7 days at both baseline and at 3 months with an RT3 accelerometer and a recall question naire . Results Observed and self-reported measures of physical activity at baseline and change in activity from baseline to 3 months were not independent predictors of RMDQ ( p > 0.05 ) or RMDQ change ( p > 0.05 ) over 3 months . A self-report of a return to full ‘ normal ’ activities was significantly associated with greater RMDQ change score at 3 months ( p activity levels measured with the RT3 ( p = 0.57 ) or the recall question naire ( p = 0.38 ) from baseline to 3 months . Conclusions These results question the predictive role of physical activity in LBP recovery , and the assumption that activity levels change as LBP symptoms resolve . The importance of a patient ’s perception of activity limitation in recovery from acute LBP was also highlighted . Trial registration Clinical Trial Registration Number ,", "Study Design . A prospect i ve cohort study of patients with episodes of acute or subacute low back pain , seeking physical therapy in primary care , with follow-up at weeks 2 , 4 , 8 , and 12 . Objectives . To evaluate the association between psychosocial factors and the transition from acute or subacute low back pain to chronicity . Summary of Background Data . Psychosocial factors have long been thought to be associated with chronic pain only . Recent prospect i ve studies , however , suggest that these factors may also be important in acute or subacute low back pain . Methods . Demographic , psychosocial , and psychological baseline data were collected and analyzed from a sample of 66 acute or subacute patients with low back pain in order to predict the 3-month outcome . Results . After 3 months , response rate was 85 % ( 56 patients ) . Forty-five percent rated their current status as “ not recovered . ” Twelve percent reported work absenteeism . Using multiple regression analyses , baseline scores on the Acute Low Back Pain Screening Question naire , Pain Coping Inventory , Fear-Avoidance Beliefs Question naire , and Tampa Scale for Kinesiophobia were not significantly associated with nonrecovery at 3 months . The only significant predictor at baseline was the subscale pain of the ALBPSQ , correctly classifying 80 % of the patients . The relative risk for not being recovered was 3.72 ( 95 % confidence interval , 1.63–8.52 ) for the subjects with high scores on the subscale for pain . Pain scores and scores on psychosocial variables at 12 weeks were not associated . Conclusions . The study strongly revealed pain-related items to be essential factors in the development of chronicity and long-term disability in primary care physical therapy . Health status at 8 weeks seems crucial in developing chronicity", "& NA ; Recently , fear – avoidance models have been quite influential in underst and ing the transition from acute to chronic low back pain ( LBP ) . Not only has pain‐related fear been found to be associated with disability and increased pain severity , but also treatment focused at reducing pain‐related fear has shown to successfully reduce disability levels . In spite of these developments , there is still a lack in well‐ design ed prospect i ve studies examining the role of pain‐related fear in acute back pain . The aim of the current study was to prospect ively test the assumption that pain‐related fear in acute stages successfully predicts future disability . Subjects were primary care acute LBP patients consulting because of a new episode of LBP ( ≤3 weeks ) . They completed question naires on background variables , fear – avoidance model variables and LBP outcome ( Grade d Chronic Pain Scale , GCPS ) at baseline , 3 , 6 , and 12 months follow‐up and at the end of the study . Two‐hundred and twenty‐two acute LBP patients were included , of whom 174 provided full follow‐up information ( 78.4 % ) . A backward ordinal regression analysis showed previous LBP history and pain intensity to be the most important predictors of end of study GCPS . Of the fear – avoidance model variables , only negative affect added to this model . Our results do not really support the longitudinal validity of the fear – avoidance model , but they do feed the discussion on the role of pain‐related fear in early stages of LBP", "Study Design . Prospect i ve inception cohort study . Objective . To investigate prospect ively whether pain-related fear predicts future perceived disability and participation in patients with acute low back pain ( LBP ) . Summary of Background Data . There are indications that fear of movement/(re)injury , as measured by the Tampa Scale for Kinesiophobia , is present early in an episode of LBP , and that it might be a predictor of future perceived disability and participation . Methods . A cohort of 555 patients with acute LBP included by general practitioners and physical therapists in primary care setting s was followed for 6 months . Results . Results indicate that baseline fear of movement/(re)injury was predictive of future perceived disability and , to a lesser extent ( and together with duration and radiation ) , of participation . Conclusions . The results suggest that interventions aim ed at reducing pain-related fear in the acute stage of LBP might prevent restrictions of activity and participation because of pain , and might be a way of preventing the transition from acute to chronic LBP", "OBJECTIVE To describe the natural course of patients with acute neck pain presenting in general practice and to identify prognostic factors for recovery and sick leave . DESIGN We conducted a prospect i ve cohort study with a 1-year follow-up in general practice . Question naires were collected at baseline and after 6 , 12 , 26 , and 52 weeks . Days of sick leave were dichotomized into two groups : below and above 7 days of sick leave . Logistic regression was used to identify prognostic factors for recovery and sick leave . PATIENTS Consecutive patients with nonspecific neck pain lasting no longer than 6 weeks were invited to participate . RESULTS One hundred eighty-seven patients were included and 138 ( 74 % ) provided follow-up data . After 1 year , 76 % of the patients stated to be fully recovered or much improved , although 47 % reported to have ongoing neck pain . Almost half of the patients on sick leave at baseline returned to work within 7 days . Multivariate analysis showed that the highest association with recovery was the advice of the general practitioner ( GP ) \" to wait and see \" ( odds ratio [ OR ] 6.7 , 95 % confidence interval [ CI ] 1.6 - 31.8 ) . For sick leave , referral by the GP , for physical therapy or to a medical specialist , showed the highest association ( OR 2.8 , 95 % CI 1.0 - 8.4 ) . CONCLUSION Acute neck pain had a good prognosis for the majority of patients , but still a relatively high proportion of patients reported neck pain after 1-year follow-up . The advice given by the GP \" to wait and see \" was associated with recovery , and \" referral \" was associated with prolonged sick leave", "UNLABELLED A r and omized controlled trial comparing manipulation with mobilization for recent onset neck pain . OBJECTIVE To determine whether neck manipulation is more effective for neck pain than mobilization . DESIGN R and omized controlled trial with blind assessment of outcome . SETTING Primary care physiotherapy , chiropractic , and osteopathy clinics in Sydney , Australia . PARTICIPANTS Patients ( N=182 ) with nonspecific neck pain less than 3 months in duration and deemed suitable for treatment with manipulation by the treating practitioner . INTERVENTIONS Participants were r and omly assigned to receive treatment with neck manipulation ( n=91 ) or mobilization ( n=91 ) . Patients in both groups received 4 treatments over 2 weeks . MAIN OUTCOME MEASURE The number of days taken to recover from the episode of neck pain . RESULTS The median number of days to recovery of pain was 47 in the manipulation group and 43 in the mobilization group . Participants treated with neck manipulation did not experience more rapid recovery than those treated with neck mobilization ( hazard ratio=.98 ; 95 % confidence interval , .66 - 1.46 ) . CONCLUSIONS Neck manipulation is not appreciably more effective than mobilization . The use of neck manipulation therefore can not be justified on the basis of superior effectiveness", "QUESTION What is the clinical course of a new episode of non-specific neck pain in people who are treated with multimodal physical therapies in a primary care setting ? DESIGN Observational study with 3-month follow-up , run in conjunction with a r and omised trial . PARTICIPANTS 181 adults who consulted a physiotherapist or chiropractor for a new episode of nonspecific neck pain . OUTCOME MEASURES Time to recover from the episode of neck pain , time to recover normal activity , and pain and neck-related disability at three months . Clinical and demographic characteristics were investigated as potential predictors of recovery . RESULTS Within 3 months , 53 % of participants reported complete recovery from the episode of neck pain . On a scale from 0 ( none ) to 10 ( worst ) , pain improved from 6.1 ( SD 2.0 ) at baseline to 2.5 ( SD 2.1 ) at 2 weeks and to 1.5 ( SD 1.8 ) at 3 months . On a scale from 0 ( none ) to 50 ( worst ) , disability improved from 15.5 ( SD 7.4 ) at baseline to 5.4 ( SD 6.4 ) at 3 months . Faster recovery was independently associated with better self-rated general health , shorter duration of symptoms , being a smoker , and absence of concomitant upper back pain or headache . Higher disability at 3 months was independently associated with higher disability at baseline , concomitant upper or lower back pain , older age , and previous sick leave for neck pain . CONCLUSION People who seek physical treatments for a new episode of neck pain in this primary care setting typically have high pain scores that improve rapidly after commencing treatment . Although almost half of those who seek treatment do not recover completely within three months , residual pain and disability in this group is relatively low . Physiotherapists should reassure people with a new episode of neck pain that rapid improvement in symptoms is common , modifying this advice where applicable based on risk factors", "& 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", "Purpose To reduce the socio-economic burden of persistent low back pain ( LBP ) , factors influencing the progression of acute/subacute LBP to the persistent state must be identified at an early stage . Methods Prospect i ve inception cohort study of patients attending a health practitioner for their first episode of acute/subacute or recurrent LBP . Patients were assessed at baseline addressing occupational , psychological , biomedical and demographic/lifestyle factors and followed up over 6 months . Multivariate logistic regression analysis was performed separately for the variables groups of the four different domains , controlling for age , gender and body mass index . The overall predictive value was calculated for the full regression models of the different domains . Finally , all significant variables from the different domains were combined into a final predictor model . Results The final four-predictor model predicted 51 % of variance of persistent LBP and included ‘ resigned attitude towards the job ’ ( OR 1.73 ; 95 % CI 1.16–2.59 ) , ‘ social support at work ’ ( OR 0.54 ; 95 % CI 0.32–0.90 ) , ‘ functional limitation ’ ( OR 1.05 ; 95 % CI 1.01–1.10 ) and ‘ duration of LBP ’ ( OR 1.04 ; 95 % CI 1.02–1.06 ) . The accuracy of the model was 83 % , with 92 % of non-persistent and 67 % of persistent LBP patients correctly identified . Conclusions In this study of patients with acute/subacute LBP , ‘ resigned attitude towards the job ’ increased the likelihood of persistent LBP at 6 month . Addressing this factor with workplace interventions has the potential to modify the outcome . In patients experiencing ‘ social support at work ’ , the development of persistent LBP was less likely and might therefore be considered as potential re source for prevention of persistent LBP", "The objective of this study was to determine predictors of onset of new headache episodes and recovery from headache over one year . A population -based cohort study was conducted , comprising a baseline postal survey to a r and om sample of adults aged ≥18 years , with follow-up survey after 1 year . Risk factor data at baseline were compared with headache status at follow-up in two groups : ( i ) those free of recent headache at baseline and ( ii ) those with a recent headache at baseline . In respondents free of recent headache at baseline , previous headache [ risk ratio ( RR ) 4.15 ] , the presence of other pain at baseline ( RR 1.43 ) , severe sleep problems ( RR 1.67 ) and drinking caffeine ( RR 1.99 ) increased the risk of a new headache episode during the follow-up year . In respondents with recent headache at baseline , less severe headaches at baseline predicted recovery during the follow-up year , as did the absence of anxiety [ recovery ratio ( ReR ) 2.84 ] and of sleep problems ( ReR 2.77 ) . Risks for increased headache-related disability reflected those for onset of a new episode and these risks increased in strength for large increases in disability . Sleep problems and caffeine consumption increase the risk of developing headache and thus provide targets for prevention . Low levels of anxiety , sleep problems and the absence of other pain improve the likelihood of recovering and remaining free from headache", "OBJECTIVE To investigate whether personal and work-related factors , physical performance and back-specific question naires predict return to work . A prospect i ve study identifying prognostic factors for return to work . SUBJECTS Ninety-three patients sick-listed for 8 - 12 weeks for non-specific sub-acute low back pain included in a r and omized controlled trial . METHODS Patients were examined with regard to demographic variables , a battery of back-specific question naires and physical tests before entering a r and omized controlled trial . A stepwise backward Cox regression model was established to identify the most powerful predictors . RESULTS During follow-up 78.5 % of the patients have returned to full-time work . Fear-avoidance beliefs for work ( relative risk ( RR ) for 1 SD change 0.49 ; 95 % confidence interval ( CI ) 0.38 - 0.64 ) , disability ( RR 1.39 , 95 % CI 1.02 - 1.88 ) and cardiovascular fitness ( RR 1.42 , 95 % CI 1.12 - 1.79 ) were identified as the best predictors for return to work . The prevalence of correct predictions was 69.3 % . CONCLUSION The predictors identified in the present study may reflect personal risk factors in a patient who gets acute low back pain . On the other h and , they may support that fear of pain and injury may be more disabling than pain itself , and that deconditioning is a result of altered behaviour reflecting attitudes towards low back pain in society , and information and advice given in primary healthcare", "Study Design . Descriptive prognostic study . Objectives . To identify outcome determinants of subacute low back pain . Summary of Background Data . The factors predicting recovery from prolonged back pain among working adults are largely unknown . Material s and Methods . One hundred sixty-four employed patients with subacute ( duration of pain 4–12 weeks ) daily low back pain were recruited from primary health care to a r and omized study . Data on potential predictive factors were collected before r and omization . In multiple regressions using repeated measures analysis , the treatment received was adjusted when determining the impact of the predictive factors . Dependent outcome variables used were pain , perceived functional disability , generic health-related quality of life , satisfaction with care , days on sick leave , use of health care , and costs of health care consumption measured , at 3- , 6- , and 12-month follow-ups . Results . Age and intensity of pain at baseline predicted most of the outcomes . The perceived risk of not recovering was a stronger determinant of outcome than gender , education , or self-rated health status ( which did not have any predictive value ) or body mass index , expectations of treatment effect , satisfaction with work , or the presence of radicular symptoms below the knee ( only slight predictive value ) . The only factors predicting the duration of sick leave were the duration of sick leave at baseline and the type of occupation . Conclusion . Age and intensity of pain are the strongest predictors of outcome . Accumulation of days on sick leave is predicted by the duration of sick leave at entry and the type of work , but not by pain , perceived disability , or satisfaction with work ", "Context In this r and omized , controlled trial , spinal manipulation plus exercise produced outcomes for low back pain similar to those produced by exercise alone . Yet , some patients did respond to spinal manipulation , and it would be helpful for doctors to be able to identify such patients . Contribution Patients were most likely to benefit from spinal manipulation if they met 4 of 5 of the following criteria : symptom duration less than 16 days , no symptoms distal to knee , score less than 19 on a fear-avoidance measure , at least 1 hypomobile lumbar segment , and at least 1 hip with more than 35 degrees of internal rotation . Implication s Clinicians may be able to use these criteria to identify patients with low back pain who are good c and i date s for spinal manipulation . The Editors Next to the common cold , low back pain is the most common reason that individuals visit a physician 's office ( 1 ) . Billions of dollars in medical expenditures and lost labor costs for this condition are incurred each year ( 2 , 3 ) . Attempts to identify effective interventions for individuals with low back pain have been largely unsuccessful ( 4 ) . In particular , conflicting evidence exists about the effectiveness of spinal manipulation ; some r and omized trials have shown a benefit , while other trials have not ( 5 - 7 ) . These conflicting conclusions are reflected in the various recommendations in national clinical practice guidelines , with some recommending manipulation and others not ( 8) . The variety of conclusions in trials of manipulation may be attributable to the failure of research ers to adequately consider the importance of classification . Using broad inclusion criteria results in a heterogeneous sample that may include many patients for whom no benefit is expected , thus masking the intervention 's true value ( 9 , 10 ) . Consequently , developing methods for matching patients with low back pain to treatments that are most likely to benefit them has become an important research priority ( 11 ) . Clinical prediction rules are tools design ed to assist clinicians in decision making when caring for patients ( 12 ) . Several clinical prediction rules have been developed and vali date d to improve clinical decision making for the use of imaging in patients with ankle , knee , cervical spine , or minor head injuries ( 13 - 16 ) . Few studies have attempted to develop rules that establish prognosis on the basis of outcome from a specific intervention , such as spinal manipulation . Recently , Flynn and colleagues ( 17 ) developed a clinical prediction rule for identifying patients with low back pain who are likely to benefit from manipulation . They examined a series of patients with low back pain who received a manipulation intervention . Five factors formed the most parsimonious set of predictors for identifying patients who achieved at least 50 % improvement in disability within 1 week with a maximum of 2 manipulation interventions ( Table 1 ) ( 17 ) . The positive likelihood ratio among patients who met at least 4 of 5 of the criteria was 24.4 ( 95 % CI , 4.6 to 139.4 ) . Table 1 . Five Criteria in the Spinal Manipulation Clinical Prediction Rule Clinical prediction rules must be vali date d in separate population s before being recommended for widespread implementation ( 18 ) . A clinical prediction rule for identifying which patients with low back pain are most likely to respond to manipulation could improve clinical efficiency and re source utilization . Thus , we aim ed to vali date the spinal manipulation clinical prediction rule in a multicenter trial . Methods We considered consecutive patients with a primary symptom of low back pain who were referred to physical therapy for participation . We used 14 physical therapists at 8 clinics in various U.S. regions and setting s ( 2 academic medical centers and smaller outpatient practice setting s ) . Most participating sites were health care facilities within the U.S. Air Force . Each site 's institutional review board approved the study before we began recruitment and data collection . Inclusion criteria were age 18 to 60 years ; a primary symptom of low back pain , with or without referral into the lower extremity ; and an Oswestry Disability Question naire ( ODQ ) score of at least 30 % . We excluded patients who had red flags for a serious spinal condition ( for example , tumor , compression fracture , or infection ) , those who had signs consistent with nerve root compression ( that is , positive straight-leg increase , those who were pregnant , or those who had previous surgery to the lumbar spine or buttock . These criteria are consistent with those used in Flynn and colleagues ' study ( 17 ) and were design ed to include patients without a contraindication to manipulation . Once patients were admitted to the study , we used intention-to-treat principles , and no patient was removed for nonadherence . History and Physical Examination Before r and omization , patients completed several self-report measures and then received a st and ardized history and physical examination . We collected demographic information , including age and sex ; medical history ; and location and nature of symptoms . Self-report measures included a body diagram to assess the symptom distribution ( 19 ) . We used an 11-point pain-rating scale ranging from 0 ( no pain ) to 10 ( worst imaginable pain ) to assess current pain intensity and the best and worst level of pain during the last 24 hours ( 20 ) . We used the average of the 3 ratings . We used the Fear-Avoidance Beliefs Question naire ( FABQ ) to quantify the patient 's fear of pain and beliefs about avoiding activity ( 21 ) . Previous studies have found a high level of testretest reliability for both the FABQ physical activity and work subscales ( 22 ) . Fearavoidance beliefs have been associated with current and future disability and work loss in patients with acute ( 23 ) and chronic ( 24 ) low back pain . The modified ODQ is a region-specific disability scale for patients with low back pain ( 25 ) that has high levels of reliability , validity , and responsiveness ( 26 ) . Physical examination measures included lumbar active range of motion ( 27 ) and various tests purported to identify dysfunction in the lumbopelvic region ( 28 ) . Complete details of the physical examination are described elsewhere ( 26 ) . Specific components pertinent to validation of the rule were assessment s of segmental mobility and hip internal rotation range of motion , the performance of which is described in Appendix 1 and Appendix 3 video . Each physical therapist received a detailed manual that operationally defined each examination and treatment procedure and was trained in the study procedures by an investigator before data collection began . Supplement . Appendix 3 video : A Clinical Prediction Rule To Identify Patients with Low Back Pain Most Likely To Benefit from Spinal Manipulation Determining Status on the Clinical Prediction Rule A physical therapist who was blinded to the patients ' treatment group assignment assessed the 5 criteria in the rule ( Table 1 , Appendix 1 , and Appendix 3 video ) . To further minimize bias , examiners were not instructed in the rule 's criteria and were unaware of the patient 's status on the rule . After completion of the study , an examiner who was blinded to the patient 's treatment assignment determined the patient 's status on the rule by using the results of the baseline examination . As was done in the initial study ( 17 ) , we classified patients as positive if they met at least 4 of 5 criteria and were therefore likely to respond to manipulation . We classified patients with 3 or fewer criteria as negative . An examiner who was blinded to the patient 's status on the rule repeated the history and physical examination 1 and 4 weeks after r and omization . Patients also completed a 6-month follow-up postal question naire to assess disability , work status , and health care utilization . Treatment Groups We used a r and om-number generator to generate a r and omization list before the study began . We prepared individual , sequentially numbered index cards with the r and omization assignments . We folded the cards and placed them in sealed envelopes . After the baseline examination , the physical therapist who conducted the examination opened the next envelope , indicating the treatment group assignment . We r and omly assigned patients to 1 of 2 groups : 1 ) spinal manipulation plus an exercise program ( manipulation group ) or 2 ) an exervideocise program alone ( exercise group ) . Patients in both groups attended physical therapy twice during the first week and then once a week for the next 3 weeks , for a total of 5 sessions . We initiated treatment immediately after completion of the baseline examination , unless prohibited by time constraints ; in that case the first treatment session took place 24 to 48 hours after the baseline examination . All patients received an exercise instruction booklet that outlined the proper performance and frequency of each exercise and were instructed to perform their assigned exercise program once daily on the days that they did not attend therapy . On the basis of the benefits associated with remaining active ( 29 ) , patients in both groups were given advice to maintain usual activity within the limits of pain . Manipulation Group The treatment received by the manipulation group differed from that of the exercise group during the first 2 physical therapy sessions . During these 2 sessions , patients received high-velocity thrust spinal manipulation and a range-of-motion exercise only . First , the physical therapist performed the manipulation by using the same technique used by Flynn and colleagues ( 17 ) . Appendix 2 describes and Figure 1 and Appendix 3 video illustrate the procedures used to perform the manipulation technique . Figure 1 . Manipulative intervention used in developing and validating the spinal manipulation clinical prediction rule . Exercise Group We treated patients in the exercise group with a low-stress", "There is a serious need to provide effective early interventions that prevent the development of persistent pain and disability . Identifying patients at risk for this development is an important step . Our aim was to explore whether distinct subgroups of individuals with similar response patterns on a screening question naire exist . Moreover , the objective was to then relate these groups to future outcomes , for example , sick leave as an impetus for developing tailored interventions that might better prevent chronic problems . A total of 363 patients seeking primary care for acute or subacute spinal pain completed the Örebro Musculoskeletal Pain Screening Question naire and were then followed to determine outcome . Cluster analysis was used to identify subgroups . Validity was tested using 3 methods including the split-half technique . The subgroups were compared prospect ively on outcome measures obtained 1 year later . Using pain intensity , fear-avoidance beliefs , function , and mood , we found 4 distinct profiles : Fear-Avoidant , Distressed Fear-Avoidant , Low Risk , and Low Risk-Depressed Mood . These 4 subgroups were also robust in all 3 of the validity procedures . The 4 subgroups were clearly related to outcome . Although the low risk profiles had virtually no one developing long-term sick leave , the Fear-Avoidant profile had 35 % and the Distressed Fear-Avoidant profile 62 % developing long-term sick leave . Our results suggest that fear-avoidance and distress are important factors in the development of pain-related disability and may serve as a key for early identification . Providing interventions specific to the factors isolated in the profiles should enhance the prevention of persistent pain and disability" ]

[ "This paper examines structured opportunities for student physical activity in Ontario elementary and secondary schools . R and om sample s of elementary and secondary schools were selected , and telephone surveys of 353 elementary and 360 secondary school personnel were conducted in 1998 . The findings indicate that elementary schools offered physical education , on average , just under three days per week . The duration of physical education class and , in some cases , the duration of vigorous physical activity in class and the weekly amount of vigorous activity in class , were significantly higher at successive grade levels . The physical education enrollment rate in secondary schools was significantly lower at successive grade levels . Student participation in secondary school intramurals and interschool sports was 22.8 % and 28.7 % respectively . These findings suggest increasing the weekly frequency of physical education in elementary schools and increasing participation in physical education classes in secondary schools . Also , intramural opportunities and participation should be promoted", "Cross-sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density ( BMD ) . However , as the exercise undertaken by athletes is beyond the reach of most individuals , these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community . To determine whether moderate exercise increases bone mass , size , areal , and volumetric BMD , two socioeconomically equivalent schools were r and omly allocated to be the source of an exercise group or controls . Twenty boys ( mean age 10.4 years , range 8.4 - 11.8 ) allocated to 8 months of 30-minute sessions of weight-bearing physical education lessons three times weekly were compared with 20 controls matched for age , st and ing and sitting height , weight , and baseline areal BMD . Areal BMD , measured using dual-energy X-ray absorptiometry , increased in both groups at all sites , except at the head and arms . The increase in areal BMD in the exercise group was twice that in controls ; lumbar spine ( 0.61 + /- 0.11 vs. 0.26 + /- 0.09%/month ) , legs ( 0.76 + /- 0.07 vs. 0.34 + /- 0.08%/month ) , and total body ( 0.32 + /- 0.04 vs. 0.17 + /- 0.06%/month ) ( all p femoral midshaft cortical thickness increased by 0.97 + /- 0 . 32%/month due to a 0.93 + /- 0.33%/month decrease in endocortical ( medullary ) diameter ( both p periosteal expansion so that volumetric BMD increased by 1.14 + /- 0.33%/month , ( p Cortical thickness and volumetric BMD did not change in controls . Femoral midshaft section modulus increased by 2.34 + /- 2 . 35 cm3 in the exercise group , and 3.04 + /- 1.14 cm3 in controls ( p exercise . Moderate and readily accessible weight-bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness . Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition , both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption", "A substantial body of cross-sectional data and a smaller number of intervention trials generally justify optimism that regular physical activity benefits the skeleton . We conducted an 8 month controlled exercise trial in a group of healthy college women ( mean age = 19.9 years ) who were r and omly assigned to a control group or to progressive training in jogging or weight lifting . We measured the following variables : bone mineral density ( BMD ) of the spine ( L2 - 4 ) and right proximal femur using dual-energy x-ray absorptiometry , dynamic muscle strength using the 1-RM method , and endurance performance using the 1.5 mile walk/run field test . A total of 31 women completed the 8 month study . For women completing the study , compliance , defined as the percentage of workout sessions attended , was 97 % for the runners ( range 90 - 100 % ) and 92 % ( range 88 - 100 % ) for the weight trainers . Body weight increased by approximately 2 kg in all groups ( p less than 0.05 ) . Weight training was associated with significant increases ( p less than 0.01 ) in muscle strength in all muscle groups . Improvement ranged from 10 % for the deep back to 54 % for the leg . No significant changes in strength scores were observed in the control or running groups . Aerobic performance improved only in the running group ( 16 % , p less than 0.01 ) . Lumbar BMD increased ( p less than 0.05 ) in both runners ( 1.3 + /- 1.6 % ) and weight trainers ( 1.2 + /- 1.8 % ) . These results did not differ from each other but were both significantly greater than results in control subjects , in whom bone mineral did not change . ( ABSTRACT TRUNCATED AT 250 WORDS", "Abstract : The maximum amount of bone a person can obtain during the first two decades of life is an important determinant of bone mass in later life , and an increase in peak bone mass has been associated with decreased risk for osteoporotic fractures . It is known that growth of bone and thus development of peak bone mass are strongly controlled by genetic factors , but information on the role of environmental factors , such as exercise and nutrition , ( e.g. , exercise ) on growing bone is limited . We tested a hypothesis that in growing girls the benefit of mechanical loading on bone mineral mass and bone strength is better before rather than after the menarche . Sixty-four girls ( 25 premenarcheal , 39 postmenarcheal ) carried out a supervised 9-month step-aerobic program ( two sessions per week ) , each session complemented with additional jumps . Sixty-two girls ( 33 premenarcheal , 29 postmenarcheal ) served as controls . Bone mineral content ( BMC ) at the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry ( DXA ) . In addition , the cortical density ( CoD , mg/cm3 ) and cortical cross-sectional area ( CoA , mm2 ) and the density-weighted polar section modulus ( BSI , mm3 ) of the tibial midshaft were determined by peripheral quantitative tomography ( pQCT ) . In the premenarcheal girls , BMC increased statistically significantly more in the trainees than controls at the lumbar spine ( p= 0.012 ) ( 8.6 % vs 5.3 % ) and femoral neck ( p= 0.014 ) ( 9.3 % vs 5.3 % ) . In the tibial midshaft , the intergroup differences ( CoD , CoA and BSI ) were not significant . The postmenarcheal girls showed no significant post-training intergroup differences in any of the bone parameters ( BMC increased in the lumbar spine 6.0 % vs 4.9 % ; femoral neck 3.4 % vs 3.2 % ; and trochanter 2.6 % vs 3.5 % ) . Although a large proportion of bone mineral increase in the growing girls of this study was attributable to growth itself , this 9-month exercise intervention showed that a clear and large additional bone gain could be obtained in exercising premenarcheal girls , but not in exercising postmenarcheal girls . In other words , exercise seemed more beneficial for additional bone mineral acquisition before menarche ( i.e. , during the growth spurt ) rather than after it", "Physical activity during childhood is advocated as one strategy for enhancing peak bone mass ( bone mineral content [ BMC ] ) as a means to reduce osteoporosis-related fractures . Thus , we investigated the effects of high-intensity jumping on hip and lumbar spine bone mass in children . Eighty-nine prepubescent children between the ages of 5.9 and 9.8 years were r and omized into a jumping ( n = 25 boys and n = 20 girls ) or control group ( n = 26 boys and n = 18 girls ) . Both groups participated in the 7-month exercise intervention during the school day three times per week . The jumping group performed 100 , two-footed jumps off 61-cm boxes each session , while the control group performed nonimpact stretching exercises . BMC ( g ) , bone area ( BA ; cm2 ) , and bone mineral density ( BMD ; g/cm2 ) of the left proximal femoral neck and lumbar spine ( L1-L4 ) were assessed by dual-energy X-ray absorptiometry ( DXA ; Hologic QDR/4500-A ) . Peak ground reaction forces were calculated across 100 , two-footed jumps from a 61-cm box . In addition , anthropometric characteristics ( height , weight , and body fat ) , physical activity , and dietary calcium intake were assessed . At baseline there were no differences between groups for anthropometric characteristics , dietary calcium intake , or bone variables . After 7 months , jumpers and controls had similar increases in height , weight , and body fat . Using repeated measures analysis of covariance ( ANCOVA ; covariates , initial age and bone values , and changes in height and weight ) for BMC , the primary outcome variable , jumpers had significantly greater 7-month changes at the femoral neck and lumbar spine than controls ( 4.5 % and 3.1 % , respectively ) . In repeated measures ANCOVA of secondary outcomes ( BMD and BA ) , BMD at the lumbar spine was significantly greater in jumpers than in controls ( 2.0 % ) and approached statistical significance at the femoral neck ( 1.4 % ; p = 0.085 ) . For BA , jumpers had significantly greater increases at the femoral neck area than controls ( 2.9 % ) but were not different at the spine . Our data indicate that jumping at ground reaction forces of eight times body weight is a safe , effective , and simple method of improving bone mass at the hip and spine in children . This program could be easily incorporated into physical education classes", "We recently demonstrated that a brief endurance type training program led to increases in thigh muscle mass and peak oxygen uptake ( VO(2 ) ) in prepubertal girls . In this study , we examined the effect of training on the GH-->insulin-like growth factor I ( GH-->IGF-I ) axis , a system known to be involved both in the process of growth and development and in the response to exercise . Healthy girls ( mean age 9.17 + /- 0.10 yr old ) volunteered for the study and were r and omized to control ( n = 20 ) and training groups ( n = 19 ) for 5 weeks . Peak VO(2 ) , thigh muscle volume , and blood sample s [ for IGF-I , IGF-binding proteins (IGFBP)-1 to -6 , and GHBP ] were measured . At baseline , IGF-I was significantly correlated with both peak VO(2 ) ( r = 0.44 , P muscle volume ( r = 0.58 , P muscle volume ( r = -0.71 , P and -5 were significantly correlated with muscle volume . We found a threshold value of body mass index percentile ( by age ) of about 71 , above which systematic changes in GHBP , IGFBP-1 , and peak VO(2 ) per kilogram were noted , suggesting decreases in the following : 1 ) GH function , 2 ) insulin sensitivity , and 3 ) fitness . Following the training intervention , IGF-I increased in control ( 19.4 + /- 9.6 % , P IGFBP-3 and GHBP decreased in the training group ( -4.2 + /- 3.1 % and -9.9 + /- 3.8 % , respectively , P prepubertal girls is associated with an activated GH-->IGF-I axis , but , paradoxically , early in a training program , children first pass through what appears to be a neuroendocrine state more consistent with catabolism", "Twenty-seven girls aged 8 to 18 were studied in a longitudinal prospect i ve fashion . Serum sample s were collected at 6 month intervals up to 4 years and radioassayed for hormones of pituitary , ovarian , and adrenal origin . A progressive elevation of luteinizing hormone ( LH ) , follicle-stimulating hormone/FSH ) , estradiol ( E2 ) , dehydroepi and rosterone ( DHA ) , and and rostenedione ( delta4 ) occurred during puberty and continued until menarche . The onset of puberty occurred concomitantly with an elevation of estrone ( E1 ) dehydroepi and rosterone ( DHA ) , dehydroepi and rosterone sulfate ( DHAS ) , and 17-hydroxyprogesterone ( 17-OH-P ) . Prolactin ( Prol ) and progesterone ( Prog ) concentrations did not change during puberty until after menarche . After menarche , levels of LH and FSH were comparable with menstruating adult females . Concentrations of E2 and Prog were lower during the second half of the cycle among most regularly menstruating subjects than expected during the luteal phase . LH and Prog levels indirectly suggest that ovulation occurs in a few girls within months after menarche", "OBJECTIVE To evaluate the effects of an elementary school-based physical education exercise intervention program on bone mineral accrual in prepubertal and early pubertal girls . STUDY DESIGN A total of 14 schools were r and omly assigned to control ( C ) and intervention ( I ) groups . Girls in the I group completed a 10-minute , 3 times per week circuit of varied jumping activities over 7 months . We measured total body , lumbar spine , proximal femur , femoral neck , and trochanteric bone mineral content and areal bone mineral density and estimated femoral neck volumetric bone mineral density at baseline and final measurement in 87 girls in the I group and 90 girls in the C group . Girls were between 8.7 and 11.7 years at baseline . Tanner stage 1 girls were considered prepubertal ; Tanner stages 2 and 3 girls were considered early pubertal . We used analysis of covariance ( adjusting for baseline bone values , change in size , age , and maturity ) to compare 7-month change in bone mineral content , areal bone mineral density , and volumetric bone mineral density between C and I groups within prepubertal and early pubertal girls . RESULTS There was no difference in 7-month change in bone parameters between prepubertal I and C groups . Early pubertal girls in the I group gained 1.5 % to 3.1 % more bone at the femoral neck and lumbar spine than early pubertal girls in the C group ( P exercise interventions to have a positive effect on bone health", "OBJECTIVES To determine the effects of up to 14 months of aerobic exercise on measures of bone density in older adults . DESIGN R and omized controlled trial with subjects assigned to either an aerobic exercise condition , non-aerobic yoga , or a wait list non-exercise control group for 4 months . Aerobic fitness and bone density were evaluated in all subjects at baseline ( Time 1 ) and after 4 months ( Time 2 ) . A semi-crossover design was utilized with all subjects completing 4 months of aerobic exercise , followed by another evaluation ( Time 3 ) . All subjects were then given the option of 6 additional months of aerobic exercise , after which they had a fourth evaluation ( Time 4 ) . SETTING An outpatient exercise rehabilitation facility at a large , major medical center . SUBJECTS One-hundred-one healthy men ( n = 50 ) and women ( n = 51 ) over age 60 ( Mean age = 67.0 ) , recruited from the community . INTERVENTION The exercise program included stretching , cycle ergometry , and walking three times per week for 60 minutes throughout the course of the study . OUTCOME MEASURES Aerobic fitness ( VO2max ) as assessed by cycle ergometry , and bone density ( bone mineral content ) measured by single photon absorptiometry . RESULTS Subjects achieved a 10%-15 % increase in VO2max after 4 months of exercise training , and 1%-6 % further improvement with additional training . Aerobic fitness was associated with significant increases in bone density in men , but not women , who maintained aerobic exercise for 14 months", "This prospect i ve 5-year follow-up study of 64 adult female racquet sports players and 27 controls assessed the changes in the playing-to-nonplaying arm bone mineral content ( BMC ) differences to answer three questions : ( 1 ) Are training-induced bone gains lost with decreased training ? ( 2 ) Is the bone response to decreased training different if the playing career has been started before or at puberty rather than after it ? ( 3 ) Are the possible bone changes related to the changes in training ? The players were divided into two groups according to the starting age of their tennis or squash playing . The mean starting age was 10.5 years ( SD , 2.2 ) among the players who had started training before or at menarche ( young starters ; n = 36 ) while 26.4 years ( SD , 8.0 ) among those players who had begun training a minimum of 1 year after menarche ( old starters ; n = 28 ) . At baseline of the 5-year follow-up , the mean age of the young starters was 21.6 years ( SD , 7.6 ) and that of old starters was 39.4 years ( SD , 10.5 ) . During the follow-up , the young starters had reduced the average training frequency from 4.7 times a week ( 2.7 ) to 1.4 times a week ( 1.3 ) and the old starters from 4.0 times a week ( 1.4 ) to 2.0 times a week ( 1.4 ) , respectively . The 5-year follow-up revealed that despite reduced training the exercise-induced bone gain was well maintained in both groups of players regardless of their clearly different starting age of activity and different amount of exercise-induced bone gain . The gain was still 1.3 - 2.2 times greater in favor of the young starters ( at the follow-up , the dominant-to-nondominant arm BMC difference was 22 % [ 8.4 ] in the humeral shaft of the young starters versus 10 % [ 3.8 ] in the old starters , and 3.5 % [ 2.4 ] in controls ) . In the players , changes in training were only weakly related to changes in the side-to-side BMC difference ( r(s ) = 0.05 - 0.34 , all NS ) , and this was true even among the players who had stopped training completely a minimum 1 year before the follow-up . In conclusion , if controlled interventions will confirm our findings that an exercise-induced bone gain can be well maintained with decreased activity and that the maintenance of the bone gain is independent of the starting age of activity , exercise can be recommended for preventing osteoporosis and related fractures", "BACKGROUND Osteoporotic fractures among the elderly are common , and without preventive measures the burden of these fractures on health-care systems will increase further . The purpose of this r and omised controlled study was to evaluate , in premenopausal women , the effects of high-impact loading on several determinants osteoporotic fractures . METHODS 98 healthy , sedentary female volunteers aged 35 - 45 years were r and omly assigned to either a training ( n = 49 ) or a control group ( n = 49 ) . Progressive high-impact exercises were done three times per week for 18 months . We measured bone mineral density ( BMD ) in specific axial and lower-limb sites , by dual-energy X-ray absorptiometry , at baseline and after 12 and 18 months . Maximum isometric strength , muscular and cardiovascular performance , and dynamic balance were also assessed . FINDINGS BMD at the femoral neck , a weightbearing site , increased significantly more in the training group ( mean 1.6 % [ 95 % CI 0.8 - 2.4 ] ) than in the control group ( 0.6 % [ -0.2 to 1.4 ] , p = 0.006 ) . By contrast , at non-weightbearing sites , such as the distal radius , there was no significant difference between the training and control groups ( -1.5 % [ -2.7 to -0.3 ] vs -0.7 % [ -1.9 to -0.5 ] , p = 0.60 ) . In the training group there was a significant improvement in vertical jump and predicted oxygen consumption per min at maximum exercise compared with controls . INTERPRETATION High-impact exercises that load bones with a rapidly rising force profile in versatile movements improve skeletal integrity , muscular performance , and dynamic balance in premenopausal women . If done on a regular basis , this type of exercise may help decrease the risk of osteoporotic fractures in later life . Long-term studies are required to show whether these 18-month results can be translated into long-term benefit", "OBJECTIVE To establish rates of skeletal mineralization in children and adolescents , and to identify factors that influence these rates . DESIGN Three-year observational study . SETTING University hospital . SUBJECTS Ninety white children , aged 6 to 14 years . MEASUREMENTS Bone mineral density of the radius , spine , and hip was measured at baseline and 3 years later . Physical activity was assessed by question naires at 6-month intervals and dietary calcium intake by diet diary 1 day per month for 36 months . Sexual maturation ( Tanner stage ) was determined by an endocrinologist at 6-month intervals , as necessary to classify children as prepubertal , peripubertal , or postpubertal . RESULTS Skeletal mineralization accelerated markedly at puberty in the spine ( 0.077 vs 0.027 gm/cm2 per year , peripubertal vs prepubertal ) and greater trochanter ( 0.050 vs 0.027 gm/cm2 per year ) , less markedly in the femoral neck ( 0.047 vs 0.030 gm/cm2 per year ) , and only slightly in the radius . Nearly one third ( 15 gm ) of the total skeletal mineral in the lumbar spine of adult women ( approximately 52 gm ) was accumulated in the 3 years around the onset of puberty . Increases in height and weight were the strongest correlates of skeletal mineralization : weight changes were more strongly correlated with trabecular bone sites and changes in height with cortical bone sites . Increases in calf muscle area were strongly associated with mineralization , particularly in peripubertal children , and physical activity was associated with more rapid mineralization in prepubertal children . CONCLUSIONS Puberty has varying effects on skeletal mineralization depending on skeletal site ; trabecular bone is apparently more sensitive to changing hormone concentrations . Physical activity and normal growth are also positively associated with skeletal mineralization , also depending on skeletal site and sexual maturation", "BACKGROUND Of the few exercise intervention studies focusing on pediatric population s , none have confined the intervention to the scheduled physical education curriculum . OBJECTIVE To examine the effect of an 8-month school-based jumping program on the change in areal bone mineral density ( aBMD ) , in grams per square centimeter , of healthy third- and fourth- grade children . STUDY DESIGN Ten elementary schools were r and omized to exercise ( n = 63 ) and control groups ( n = 81 ) . Exercise groups did 10 tuck jumps 3 times weekly and incorporated jumping , hopping , and skipping into twice weekly physical education classes . Control groups did regular physical education classes . At baseline and after 8 months of intervention , we measured aBMD and lean and fat mass by dual-energy x-ray absorptiometry ( Hologic QDR-4500 ) . Calcium intake , physical activity , and maturity were estimated by question naire . RESULTS The exercise group showed significantly greater change in femoral trochanteric aBMD ( 4.4 % vs 3.2 % ; P ( baseline aBMD change in height , change in lean , calcium , physical activity , sex , and ethnicity ) in hierarchical regression . CONCLUSIONS An easily implemented school-based jumping intervention augments aBMD at the trochanteric region in the prepubertal and early pubertal skeleton", "We compared 7-month changes in bone structural properties in pre- and early-pubertal girls r and omized to exercise intervention ( 10-minute , 3 times per week , jumping program ) or control groups . Girls were classified as prepubertal ( PRE ; Tanner breast stage 1 ; n = 43 for intervention [ I ] and n = 25 for control [ C ] ) or early-pubertal ( EARLY ; Tanner stages 2 and 3 ; n = 43 for I and n = 63 for C ) . Mean + /- SD age was 10.0 + /- 0.6 and 10.5 + /- 0.6 for the PRE and EARLY groups , respectively . Proximal femur scans were analyzed using a hip structural analysis ( HSA ) program to assess bone mineral density ( BMD ) , subperiosteal width , and cross-sectional area and to estimate cortical thickness , endosteal diameter , and section modulus at the femoral neck ( FN ) , intertrochanter ( IT ) , and femoral shaft ( FS ) regions . There were no differences between intervention and control groups for baseline height , weight , calcium intake , or physical activity or for change over 7 months ( p > 0.05 ) . We used analysis of covariance ( ANCOVA ) to examine group differences in changes of bone structure , adjusting for baseline weight , height change , Tanner breast stage , and physical activity . There were no differences in change for bone structure in the PRE girls . The more mature girls ( EARLY ) in the intervention group showed significantly greater gains in FN ( + 2.6 % , p = 0.03 ) and IT ( + 1.7 % , p = 0.02 ) BMD . Underpinning these changes were increased bone cross-sectional area and reduced endosteal expansion . Changes in subperiosteal dimensions did not differ . Structural changes improved section modulus ( bending strength ) at the FN ( + 4.0 % , p = 0.04 ) , but not at the IT region . There were no differences at the primarily cortical FS . These data provide insight into geometric changes that underpin exercise-associated gain in bone strength in early-pubertal girls" ]

[ "The chair-side work posture of dental hygienists has long been a concern because of health-related problems potentially caused or exacerbated by poor posture . The purpose of this study was to investigate if using magnification loupes improved dental hygiene students ' posture during provision of treatment . The treatment chosen was h and -scaling , and the effect of the timing of introduction of the loupes to students was also examined . Thirty-five novice dental hygiene students took part in the study . Each student was assessed providing dental hygiene care with and without loupes , thus controlling for innate differences in natural posture . Students were r and omized into two groups . Group one used loupes in the first session and did not use them for the second session . Group two reversed this sequence . At the end of each session , all students were videotaped while performing scaling procedures . Their posture was assessed using an adapted version of Branson et al. 's Posture Assessment Instrument ( PAI ) . Four raters assessed students at three time periods for nine posture components on the PAI . A paired t-test compared scores with and without loupes for each student . Scores showed a significant improvement in posture when using loupes ( p improvements were significantly more pronounced for students starting loupes immediately on entering the program compared with students who delayed until the second session ( p postural benefit is realized by requiring students to master the use of magnification loupes as early as possible within the curriculum", "Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers", "Background Work-related musculoskeletal disorders commonly experienced by dental professionals are one of the main occupational health problem affecting their health and well-being . This study was conducted to evaluate ergonomic factors and profession-related postures and also investigate relationship between demographic factors and work condition with pain in dental students . Material and Methods 60 freshman and sophomore dentistry students were r and omly chosen as the subjects of control group , and 60 of 5th and 6th-year students were selected as the members of exposure group . Data related to the subjects such as sex , doing exercise , severity of musculoskeletal pain were obtained through question naire . Students ’ postures were directly observed while treating patients and they were scored by REBA method . Data were analyzed by SPSS software using Man-Whitney , Kruskal-Wallis , Spearman and Kendall correlation tests . Results 80.8 % of the subjects were not aware of the correct ergonomic postures for dental procedures . Severity of musculoskeletal pain in the exposure group ( 15.9± 4.2 ) was significantly higher than the control group ( 10.5 ±3.2 ) , ( p more muscular pains . Conclusions The musculoskeletal disorders are probable prolonged in working hours in static positions , incorrect work postures , implying more force and even tools and instruments . Therefore , students who are aware of ergonomic principals of their own profession would be able to maintain their health through activities and lifelong . Key words : Posture , dentistry , students , musculoskeletal pain", "OBJECTIVE To study the relation between neck pain and work related neck flexion , neck rotation , and sitting . METHODS A prospect i ve cohort study was performed with a follow up of 3 years among 1334 workers from 34 companies . Work related physical load was assessed by analysing objective ly measured exposure data ( video recordings ) of neck flexion , neck rotation , and sitting posture . Neck pain was assessed by a question naire . Adjustments were made for various physical factors that were related or not related to work , psychosocial factors , and individual characteristics . RESULTS A significant positive relation was found between the percentage of the working time in a sitting position and neck pain , implying an increased risk of neck pain for workers who were sitting for more than 95 % of the working time ( crude relative risk ( RR ) 2.01 , 95 % confidence interval ( 95 % CI ) 1.04 to 3.88 ; adjusted RR 2.34 , 95 % CI 1.05 to 5.21 ) . A trend for a positive relation between neck flexion and neck pain was found , suggesting an increased risk of neck pain for people working with the neck at a minimum of 20 ° of flexion for more than 70 % of the working time ( crude RR 2.01 , 95 % CI 0.98 to 4.11 ; adjusted RR 1.63 , 95 % CI 0.70 to 3.82 ) . No clear relation was found between neck rotation and neck pain . CONCLUSION Sitting at work for more than 95 % of the working time seems to be a risk factor for neck pain and there is a trend for a positive relation between neck flexion and neck pain . No clear relation was found between neck rotation and neck pain", "A joint study was conducted by a manufacturer of dental stools in the Midwest of the United States and Marquette University to measure the occupational postures of dentists and dental hygienists . The postures of 10 dentists and 10 dental hygienists were assessed using work sampling and video techniques . Postural data of the neck , shoulders and lower back were recorded from video and categorized into 30-degree intervals : o ( neutral posture of respective joint ) , 30 , 60 and 90 degrees . Each subject 's postures were observed while they were treating patients during a four-hour period , during which 100 observations of postures were recorded at r and om times . Compared to st and ing , dentists and dental hygienists were seated 78 percent and 66 percent of the time , respectively . Dentists and dental hygienists flexed their trunk at least 30 degrees more than 50 percent of the time . They flexed their neck at least 30 degrees 85 percent of the time during the four-hour duration , and their shoulders were elevated to the side of their trunk ( abducted ) at least 30 degrees more half of the time . The postures of the trunk , shoulders , and neck were primarily static . This data base of postures can be used by dental professionals and ergonomists to assess the risk dentists and dental hygienists are exposed to musculoskeletal disorders , such as low back pain or shoulder tenosynovitis , from deviated joint postures . They could use these data to select dental furniture or dental devices that promote good body posture , i.e. , reduce the magnitude and duration of deviated joint postures , which , in theory , would decrease the risk of musculoskeletal disorders", "OBJECTIVE optical magnifying devices such as magnification loupes are increasingly used in clinical practice and educational setting s. However , scientific evidence to vali date their benefits is limited . This study assessed the effect of dental magnification loupes on psychomotor skill acquisition during a pre clinical operative dentistry course . METHOD AND MATERIAL S the performance of first-year dental students was assessed during an Advanced Simulation Course ( AS ) using virtual reality-based technology ( VRBT ) training . The test group consisted of 116 dental students using magnification loupes ( + MAG ) , while students not using them ( -MAG , n = 116 ) served as the control . The following parameters were evaluated : number of successfully passing preparation procedures per course rotation , amount of time per tooth preparation , number of times students needed computer assistance and evaluation , and amount of time spent in the computer assistance and evaluation mode per procedure . Data were collected on each student through VRBT during the preparation procedure and stored on a closed network server computer . Unpaired t tests were used to analyze mean differences between the groups . In addition , student acceptance of magnification loupes was measured and evaluated through survey interpretation . RESULTS + MAG students completed more preparations , worked faster per procedure , and used the computer-assisted evaluation less frequently and for shorter periods , therefore displaying greater overall performance . The survey revealed a high degree of student acceptance of using magnification . CONCLUSION dental magnification loupes significantly enhanced student performance during pre clinical dental education and were considered an effective adjunct by the students who used them", "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", "BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application", "A distinct body of literature supports the association between clinical postures of the dental practitioner and work-related musculoskeletal disorders ( WRMD ) . Several aids or devices have been tested to improve clinical posture in the interest of decreasing WRMD . The use of magnification lenses while performing dental procedures may increase the quality of work and decrease the likelihood of musculoskeletal problems . To date , only anecdotal and personal opinions had existed regarding the benefits of using magnification lenses , and no empirical evidence had authenticated the contention that use of magnification lenses exerts a positive change in operator posture . The objective of this study was to assess the effect magnification lenses had on the posture of dental hygiene students . Using a r and omized crossover design , research ers videotaped nineteen senior dental hygiene students performing an intra-oral procedure with and without the use of magnification lenses . The tapes were then evaluated by a panel of five dental hygiene educators calibrated in the use of Branson 's Posture Assessment Instrument ( PAI ) . Results of a paired t-test indicate that the posture of the students while wearing magnification lenses was more acceptable ( p=.019 ) than when wearing traditional safety glasses . Results of this study indicate a quantifiable change in acceptability of posture for clinicians wearing magnification lenses and suggest that the use of such lenses in dental education may be warranted", "The aim of this analytical cross-sectional study was to evaluate the presence of work-related musculoskeletal disorders ( WMSD ) among dental students in two Brazilian dental schools . The sample included 227 r and omized subjects from fifth to ninth semesters who were developing clinical activities . Each student signed an informed consent form . A self-reporting question naire was used to obtain data on the practice of physical exercise , the presence of pain during or soon after treating patients , and the adoption of preventive measures related to clinical activities . Results were analyzed using the Statistical Package for Social Sciences 13.0 . The chi(2 ) test was used to identify associations between variables . The presence of pain during or after clinical work was reported by 173 participants ( 76.2 percent ) . Statistically significant differences were found between gender and the occurrence of pain . Pain was present during clinical activities ( p=0.006 ) and imposed limitations on the work routine ( p=0.011 ) . Among those who practice d physical exercise , eighty-eight ( 74.6 percent ) reported pain . The high percentage of pain reported by dental students suggests the value of review ing work conditions in dental practice s in order to minimize the exposure of all workers to WMSD" ]

[ "Several authors have demonstrated the pivotal role of proinflammatory cytokines in inducing progressive cartilage degradation and secondary inflammation of the synovial membrane in osteoarthritis ( OA ) . It has recently been established that tumor necrosis factor (TNF)-alpha plays a well-defined role in the pathophysiology of inflammatory joint diseases and that binding to circulating soluble TNF-alpha receptors can inactivate it . We investigated the influence of mud pack treatment , which is able to diminish TNF-alpha serum values , on specific TNF receptor ( sTNF-R ) levels . Thirty-six patients with OA were enrolled and r and omized into two groups . Group A underwent mud pack treatment and group B underwent thermal bath treatment . A group of 20 healthy untreated subjects was used as a control . Blood sample s were collected at baseline and after treatment , and assays of sTNF-R55 and sTNF-R75 were performed in both groups . We found small changes in sTNF-Rs serum values but these were not statistically significant . sTNF-R55 serum values decreased by 0.4 % after the therapy in group A , while in group B the decrease was -17.7 % . sTNF-R75 was reduced by -21.17 % in group A and by -10.6 % in group B. In conclusion , through its thermic and ant/inflammatory activity mud pack treatment shows complex interaction with the most common factors of inflammatory and cartilage degradation . Our results suggest that the thermic component of this natural treatment is mainly involved in modulating inflammatory reaction and cartilage damage through binding of the circulating TNF , which controls the activation of the cells responsible for the production of proinflammatory cytokines", "OBJECTIVES To compare the differences or correlation between the results obtained from a generic and a disease-specific instrument for the study group and to assess the short-term effects of spa therapy on quality of life of patients with knee osteoarthritis . PATIENTS AND METHODS Fifty patients with knee osteoarthritis were r and omly recruited . They underwent a comprehensive spa therapy program for 21 days . Forty-six patients completed the study . The results were evaluated with Medical Outcomes Study 36-Item Short Form-36 ( SF-36 ) and Arthritis Impact Measurement Scale 2 ( AIMS 2 ) . RESULTS Statistically significant improvement was observed in all subscales of SF-36 . All subscales of AIMS 2 improved too , but only half of them were significant . Correlation between matching subscales of each test was also significant , except physical activity . CONCLUSION Comprehensive spa therapy seems to increase the quality of life of patients with knee osteoarthritis for short term", "Mud-bath therapy plays a primary role in the treatment and prevention of osteoarthritis that has been recognised since antiquity . Numerous studies have demonstrated its clinical benefits and its effects on inflammatory mediators ( interleukins ) , the immune system , cenesthesic factors ( endorphins ) , and the diencephalic – pituitary – adrenal axis . This study was conducted to assess the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy ’s Chianciano Spa in patients with osteoarthritis of the knee . Patients ( n = 61 ) were divided into two groups . Group A underwent three cycles of mud-based spa therapy over a year ’s time , whereas group B did not . Clinical conditions , visual analogue scale pain ratings , and Lequesne indexes of the two groups were compared . We also compared these same parameters in the patients of the two groups that were following the therapy with drugs and in the patients of the group A before and after spa treatment . The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B. Within group A , this percentage was higher after treatment than before spa therapy . Even in the comparison between the patients of the two groups that were following the therapy with drug , the results was that in group A the percentage of patients with no symptoms or mild symptoms was higher than in group B. Statistical analyses based on various tests revealed that almost all these differences were highly significant . No adverse effects were observed in any of the patients in group A. In conclusion , the mud-bath therapy performed at Chianciano Spa with Sillene Spring water remarkably improved the clinical conditions of patients with knee arthritis and significantly reduces the frequency and severity of symptoms and the disability they cause", "Mud pack therapy is an alternative mode of treatment for rheumatic diseases . It is based on the application of heated mud packs to the entire body or to specific areas , such as over joints . The aim of the current study was to evaluate the efficacy of treatment with mud compresses at patients ’ homes for osteoarthritis of the knee . Fifty-eight patients with osteoarthritis of the knee were enrolled in a prospect i ve , double-blinded , controlled study . Forty patients were treated with natural mineral-rich mud compresses and 18 patients were treated with mineral-depleted mud compresses . Mud compresses were applied 5 times each week during 3 weeks for a total of 15 treatments . Patients were assessed at baseline , at completion of the 3-week treatment period , and twice after the conclusion of the treatment period — after 1 month and after 3 months . The main outcome measures were the Lequesne Index of severity of knee osteoarthritis , patient self- assessment of pain , and severity of knee pain on a visual analog scale . A reduction of 20 % or more in the pain scores was considered clinical ly significant . In the group treated with natural mud compresses , a significant reduction in knee pain was observed at all assessment s. Similarly , improvement in the Lequesne Index was seen at the end of therapy and a month after treatment . In the control group , given mineral-depleted mud compresses , no significant change in knee pain was seen at any assessment . Improvement in the Lequesne Index was seen 1 and 3 months after completion of the therapy , but not at the end of therapy . Seventy-two percent of the patients in the treatment group had an improvement of > 20 % in self- assessment of knee pain , compared with 33 % in the control group ( p = 0.005).The data suggest that treatment with mud compresses , but only in their natural form , temporarily relieves pain in patients with osteoarthritis of the knees . We believe that treatment with mud compresses might augment conventional medical therapy in these patients", "Objective To determine whether spa therapy , plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment , in the management of knee osteoarthritis . Methods Large multicentre r and omised prospect i ve clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria , attending French spa resorts as out patients between June 2006 and April 2007 . Zelen r and omisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating . The main endpoint criteria were patient self-assessed . All patients continued usual treatments and performed daily st and ardised home exercises . The spa therapy group also received 18 days of spa therapy ( massages , showers , mud and pool sessions ) . Main Endpoint The number of patients achieving minimal clinical ly important improvement ( MCII ) at 6 months , defined as ≥19.9 mm on the visual analogue pain scale and /or ≥9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery . Results The intention to treat analysis included 187 controls and 195 spa therapy patients . At 6 months , 99/195 ( 50.8 % ) spa group patients had MCII and 68/187 ( 36.4 % ) controls ( χ2=8.05 ; df=1 ; p=0.005 ) . However , no improvement in quality of life ( Short Form 36 ) or patient acceptable symptom state was observed at 6 months . Conclusion For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone , and is well tolerated . Trial registration number NCT00348777", "The aims of this study were to evaluate whether balneotherapy with mineral sulphate – bicarbonate – calcium water could determine substantial symptomatic improvement , and to detect any changes in the quality of life ( QoL ) of patients with symptomatic knee osteoarthritis ( OA ) . This was a prospect i ve r and omized , single blind controlled trial . Sixty out patients with primary bilateral knee OA , according to ACR criteria , were included in the study and r and omized to one of two groups : group I ( 30 patients ) was treated with a daily sulphate – bicarbonate – calcium mineral water bath ; group II ( 30 patients ) , the control group , continued their regular outpatient care routine . At baseline , after 15 days and after 12 weeks , patients were evaluated by Visual Analogue Scale ( VAS ) for spontaneous pain , Lequesne and Womac Index for gonarthrosis , SF-36 , Arthritis Impact Measurement Scale ( AIMS ) and symptomatic drugs consumption . We observed a significant improvement of all parameters at the end of the cycle of balneotherapy which persisted throughout the follow-up period , whereas in the control group no significant differences were noted . This symptomatic effect was confirmed by the significant reduction of symptomatic drugs consumption . The differences between the two groups were significant for all considered parameters already from the 15th day and persisted during follow-up . Tolerability of balneotherapy seemed to be good , with light and transitory side effects . Our results confirm that the beneficial effects of balneotherapy in patients with knee OA last over time , with positive effects on the painful symptomatology , a significant improvement on functional capacities and QoL. Balneotherapy can represent a useful backup to pharmacological treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments", "Nitric oxide ( NO ) has recently been proposed as an important mediator in inflammatory phases and in loss of cartilage . In inflammatory arthritis NO levels are correlated with disease activity and articular cartilage is able to produce large amounts of NO with the appropriate inducing factors such as cytokines and /or endotoxin . Neutrophils also play an important role in inflammatory reactions and the level of myeloperoxidase , a constituent of neutrophil granules , is related to the intensity of the inflammation . Because there is evidence that suggests that mud packs influence the main cytokines involved in cartilage damage , we tried to determine whether NO and myeloperoxidase are involved in the mechanisms of action of mud bath treatment . We enrolled 37 subjects and r and omly assigned them to two groups : 19 patients underwent mud bath treatment ( group A ) while 18 patients underwent bath treatment alone . Blood sample s were obtained before and after the treatment cycles to assay serum levels of NO , myeloperoxidase ( MPO ) and glutathione (GSH)-peroxidase . The results showed a statistically significant decrease in NO and myeloperoxidase serum values in groups A and B , while GSH-peroxidase was not significantly increase in either of the groups ; no correlation was found between NO , myeloperoxidase and GSH-peroxidase serum values . Mud bath treatment can exert beneficial effects on cartilage homeostasis and inflammatory reactions , influencing NO and decreasing myeloperoxidase serum values . The increase in GSH-peroxidase was not correlated with the reduction of other biochemical markers , suggesting that mud bath treatment has different mechanisms of action", "Spa therapy and short wave therapy are two of the most commonly used non-pharmacological approaches for osteoarthritis . The aim of this study was to assess their efficacy in comparison to conventional therapy in patients with osteoarthritis of the knee in a single blind , r and omized , controlled trial . Seventy-four out patients were enrolled ; 30 patients were treated with a combination of daily local mud packs and arsenical ferruginous mineral bath water from the thermal resort of Levico Terme ( Trento , Italy ) for 3 weeks ; 24 patients were treated with short wave therapy for the same period and 20 patients continued regular , routine ambulatory care . Patients were assessed at baseline , upon completion of the 3-week treatment period , and 12 weeks later . Spa therapy and short wave therapy both demonstrated effective symptomatic treatment in osteoarthritis of the knee at the end of the treatment , but only the spa therapy was shown to have efficacy persistent over time . Our study demonstrated the superiority of arsenical ferruginous spa therapy compared to short wave therapy in the treatment of osteoarthritis of the knee , probably in relationship to the specific effects of the minerals in this water", "The objective of the study was to investigate the efficacy and tolerability of the peloid plasters in the group of 20 patients with osteoarthritis of peripheral joints ( 10 patients with gonarthrosis and 10 with omarthrosis ) and 20 patients with spondylosis . This form of the pelotherapy decreased pain in joints after 10 days of the treatment . No allergic or other side effects were observed . Peloid plasters through the analgesic action improve the comfort of life and reduce the use of oral analgesic drugs", "We have previously shown that thermal mud therapy is able to influence chondrocyte activity of osteoarthrosic patients by modulating the production of serum cytokines , such as interleukin 1 , and this was related to the presence of an anti-inflammatory principle in mature thermal mud . Mud therapy influences many biochemical processes of the body , independently of the thermic stimulation alone and the present paper documents specific increases of insulin growth factor 1 and decreases of tumor necrosis factor alpha in serum of osteoarthrosic patients after 12 days of mud pack application", "OBJECTIVES Knee osteoarthritis ( OA ) is a common chronic degenerative disorder . There are various treatment modalities . This study was planned to investigate the efficacy of balneotherapy , mud-pack therapy in patients with knee OA . METHODS A total of 80 patients with knee OA were included . Their ages ranged between 39 - 78 . The patients were separated in to three groups . Group I ( n=25 ) received balneotherapy , group II ( n=29 ) received mud-pack therapy and group III ( n=26 ) was hot-pack therapy group . The therapies were applied for 20 min duration , once a day , five times per week and a total of 10 session . Patients were assessed according to pain , functional capacity and quality of life parameters . Pain was assessed by using Visual Analogue Scale ( VAS ) and Western Ontario McMaster Osteoarthritis Index ( WOMAC ) pain scale ( 0 - 4 likert scale ) . Functional capacity was assessed by using WOMAC functional capacity and WOMAC global index . Quality of life was evaluated by Nottingham Health Profile ( NHP ) self-administered question naire . Also physician 's global assessment and the maximum distance that patient can walk without pain , were evaluated . The assessment parameters were evaluated before and after three months . RESULTS There were statistically significant improvement in VAS and WOMAC pain scores in group I ( p WOMAC functional and global index also decreased in group I ( p Quality of life results were significantly improved in balneotherapy and mud-pack therapy groups ( p in hot-pack therapy group ( p>0.05 ) . The maximum distance was improved both in group I and II ( p physician 's global assessment was found to be improved in all groups ( p CONCLUSIONS Balneotherapy and mud-pack therapy were effective in treating patients with knee OA", "Osteoarthritis is an important rheumatic condition characterized by the progressive destruction of cartilage . The pathophysiologic phenomena leading to the pathologic changes in the joint appear to result from biomechanical factors and activation of final common pathways of tissue damage influencing chondrocyte homeostasis and a functional program . Several cytokines and growth factors are reported to be responsible for inflammation and cartilage degradation . Among these , IL-1 and TNF alpha have been suggested as important in promoting cartilage inflammation and tissue destruction , while IGF I has a protective influence on cartilage structure . Chondrocytes and their metabolism have gained interest as targets of drug intervention ; the results of this study confirm that mud bath therapy is also able to influence chondrocyte activities . Our data suggest that mud bath therapy influences cytokines related to osteoarthrosis pathomechanism and maintenance , and encourage further investigations to evaluate possible synergism between pharmacological treatment and mud bath therapy", "Fioravanti A , Iacoponi F , Bellisai B , Cantarini L , Galeazzi M : Short- and long-term effects of spa therapy in knee osteoarthritis . Objective : To assess both the short- and long-term effectiveness of spa therapy in patients with primary knee osteoarthritis in a prospect i ve , r and omized , single-blinded , controlled trial . Design : Eighty out patients were enrolled in this study ; 40 patients were treated with a combination of daily local mud packs and bicarbonate-sulfate mineral bath water from the spa center of Rapolano Terme ( Siena , Italy ) for 2 wks , and 40 patients continued regular , routine ambulatory care . Patients were assessed at baseline time ; after 2 wks ; after 3 , 6 , and 9 mos after the beginning of the study and were evaluated by Visual Analog Scale for spontaneous pain , Lequesne index , Western Ontario and McMaster Universities Index for gonarthrosis , Arthritis Impact Measurement Scale-1 , and symptomatic drug consumption . Results : We observed a significant improvement of all evaluated parameters at the end of the cycle of spa therapy , which persisted throughout the whole of the follow-up period , whereas in the control group no significant differences were noted . This symptomatic effect was confirmed by the significant reduction of symptomatic drug consumption . Tolerability of spa therapy seemed to be good , with light and transitory side effects . Conclusions : The results from our study confirm that the beneficial effects of spa therapy in patients with knee osteoarthritis lasts over time , with positive effects on the painful symptomatology and a significant improvement on functional capacities . Spa therapy can represent a useful backup to pharmacologic treatment of knee osteoarthritis or a valid alternative for patients who do not tolerate pharmacologic treatments" ]

[ "There is a pressing need for additional treatment options for refractory mood disorders . This controlled comparative study evaluated the efficacy of lamotrigine ( LTG ) and gabapentin ( GBP ) monotherapy versus placebo ( PLC ) . Thirty-one patients with refractory bipolar and unipolar mood disorders participated in a double-blind , r and omized , crossover series of three 6-week monotherapy evaluations including LTG , GBP , and PLC . There was a st and ardized blinded titration to assess clinical efficacy or to determine the maximum tolerated daily dose ( LTG 500 mg or GBP 4,800 mg ) . The primary outcome measure was the Clinical Global Impressions Scale ( CGI ) for Bipolar Illness as supplemented by other st and ard rating instruments . The mean doses at week 6 were 274 + /- 128 mg for LTG and 3,987 + /- 856 mg for GBP . Response rates ( CGI ratings of much or very much improved ) were the following : LTG , 52 % ( 16/31 ) ; GBP , 26 % ( 8/31 ) ; and PLC , 23 % ( 7/31 ) ( Cochran 's Q = 6.952 , df = 2 , N = 31 , p = 0.031 ) . Post hoc Q differences ( df = 1 , N = 31 ) were the following : LTG versus GBP ( Qdiff = 5.33 , p = 0.011 ) ; LTG versus PLC ( Qdiff = 4.76 , p = 0.022 ) ; and GBP versus PLC ( Qdiff = 0.08 , p = 0.70 ) . With respect to anticonvulsant dose and gender , there was no difference between the responders and the nonresponders . The agents were generally well tolerated . This controlled investigation preliminarily suggests the efficacy of LTG in treatment-refractory affectively ill patients . Further definition of responsive subtypes and the role of these medications in the treatment of mood disorders requires additional study", "OBJECTIVE To determine the efficacy of divalproex ( extended release ) in the treatment of acute nonrefractory bipolar depression . METHOD In a stratified , double-blind , r and omized , placebo-controlled trial , 18 acutely depressed bipolar out patients ( DSM-IV criteria ) received either divalproex monotherapy ( target dose level , 70 - 90 ng/dL ) ( N = 9 ) or placebo ( N = 9 ) for 6 weeks . Patients were recruited between January 2004 and May 2005 . Clinical assessment on the Montgomery-Asberg Depression Rating Scale ( MADRS ) determined primary efficacy . RESULTS The divalproex treatment group showed significantly greater reduction in MADRS scores compared to placebo ( group x time interaction , p = .0078 ) . Absolute effect size of estimated MADRS total score reduction over time was 13.6 points with divalproex versus 1.4 points with placebo ( p = .003 , linear growth curve model ) . St and ardized effect size was large ( Cohen d = 0.81 ) . MADRS item analyses demonstrated improvement in core mood symptoms more than in anxiety or insomnia symptoms . There was also a modest but significant association between MADRS and Mania Rating Scale scores in the divalproex group ( r = 0.29 , df = 51 , p = .03 ) , but not in the placebo group ( r = -0.15 , df = 35 , p = .36 ) . CONCLUSIONS Divalproex appeared to be an effective treatment for acute nonrefractory bipolar depression , which is consistent with previous small r and omized studies . Some evidence of benefit in the depressive mixed state was observed . Confirmation or refutation with larger r and omized clinical trials is warranted . CLINICAL TRIAL REGISTRATION Clinical Trials.gov identifier NCT00226343", "BACKGROUND To our knowledge , this is the first prospect i ve natural history study of weekly symptomatic status of patients with bipolar I disorder ( BP-I ) during long-term follow-up . METHODS Analyses are based on ongoing prospect i ve follow-up of 146 patients with Research Diagnostic Criteria BP-I , who entered the National Institute of Mental Health ( Bethesda , Md ) Collaborative Depression Study from 1978 through 1981 . Weekly affective symptom status ratings were analyzed by polarity and severity , ranging from asymptomatic , to subthreshold levels , to full-blown major depression and mania . Percentages of follow-up weeks at each level as well as number of shifts in symptom status and polarity during the entire follow-up period were examined . Finally , 2 new measures of chronicity were evaluated in relation to previously identified predictors of chronicity for BP-I. RESULTS Patients with BP-I were symptomatically ill 47.3 % of weeks throughout a mean of 12.8 years of follow-up . Depressive symptoms ( 31.9 % of total follow-up weeks ) predominated over manic/hypomanic symptoms ( 8.9 % of weeks ) or cycling/mixed symptoms ( 5.9 % of weeks ) . Subsyndromal , minor depressive , and hypomanic symptoms combined were nearly 3 times more frequent than syndromal-level major depressive and manic symptoms ( 29.9 % vs 11.2 % of weeks , respectively ) . Patients with BP-I changed symptom status an average of 6 times per year and polarity more than 3 times per year . Longer intake episodes and those with depression-only or cycling polarity predicted greater chronicity during long-term follow-up , as did comorbid drug-use disorder . CONCLUSIONS The longitudinal weekly symptomatic course of BP-I is chronic . Overall , the symptomatic structure is primarily depressive rather than manic , and subsyndromal and minor affective symptoms predominate . Symptom severity levels fluctuate , often within the same patient over time . Bipolar I disorder is expressed as a dimensional illness featuring the full range ( spectrum ) of affective symptom severity and polarity", "BACKGROUND Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials . This double-blind , placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder . METHODS After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued , patients were r and omized to lamotrigine ( 100 - 400 mg daily ) , lithium ( 0.8 - 1.1 mEq/L ) , or placebo as double-blind maintenance treatment for as long as 18 months . RESULTS Of 349 patients who met screening criteria and entered the open-label phase , 175 met stabilization criteria and were r and omized to double-blind maintenance treatment ( lamotrigine , 59 patients ; lithium , 46 patients ; and placebo , 70 patients ) . Both lamotrigine and lithium were superior to placebo at prolonging the time to intervention for any mood episode ( lamotrigine vs placebo , P = .02 ; lithium vs placebo , P = .006 ) . Lamotrigine was superior to placebo at prolonging the time to a depressive episode ( P = .02 ) . Lithium was superior to placebo at prolonging the time to a manic , hypomanic , or mixed episode ( P = .006 ) . The most common adverse event reported for lamotrigine was headache . CONCLUSIONS Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode . The results indicate that lamotrigine is an effective , well-tolerated maintenance treatment for bipolar disorder , particularly for prophylaxis of depression", "OBJECTIVE Clinicians have few evidence -based options for the management of treatment-resistant bipolar depression . This study represents the first r and omized trial of competing options for treatment-resistant bipolar depression and assesses the effectiveness and safety of antidepressant augmentation with lamotrigine , inositol , and risperidone . METHOD Participants ( N=66 ) were patients with bipolar I or bipolar II disorder enrolled in the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) . All patients were in a current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant . Patients were r and omly assigned to open-label adjunctive treatment with lamotrigine , inositol , or risperidone for up to 16 weeks . The primary outcome measure was the rate of recovery , defined as no more than two symptoms meeting DSM-IV threshold criteria for a mood episode and no significant symptoms present for 8 weeks . RESULTS No significant between-group differences were seen when any pair of treatments were compared on the primary outcome measure . However , the recovery rate with lamotrigine was 23.8 % , whereas the recovery rates with inositol and risperidone were 17.4 % and 4.6 % , respectively . Patients receiving lamotrigine had lower depression ratings and Clinical Global Impression severity scores as well as greater Global Assessment of Functioning scores compared with those receiving inositol and risperidone . CONCLUSIONS No differences were found in primary pairwise comparison analyses of open-label augmentation with lamotrigine , inositol , or risperidone . Post hoc secondary analyses suggest that lamotrigine may be superior to inositol and risperidone in improving treatment-resistant bipolar depression", "BACKGROUND Sub-syndromal symptoms in bipolar disorder impair functioning and diminish quality of life . AIMS To examine factors associated with time spent with sub-syndromal symptoms and to characterise how these symptoms influence outcomes . METHOD In a double-blind r and omised maintenance trial , patients received either olanzapine or lithium monotherapy for 1 year . Stepwise logistic regression models were used to identify factors that were significant predictors of percentage time spent with sub-syndromal symptoms . The presence of sub-syndromal symptoms during the first 8 weeks was examined as a predictor of subsequent relapse . RESULTS Presence of sub-syndromal depressive symptoms during the first 8 weeks significantly increased the likelihood of depressive relapse ( relative risk 4.67 , P Patients with psychotic features and those with a greater number of previous depressive episodes were more likely to experience sub-syndromal depressive symptoms ( RR=2.51 , P patients at increased risk of affective relapse and suggest that appropriate therapeutic interventions should be considered even when syndromal-level symptoms are absent", "The authors evaluated carbamazepine ( Tegretol ) , a drug of choice for treatment of temporal lobe epilepsy , in a double-blind placebo-controlled trial in patients with manic-depressive illness . Seven of 9 manic patients had a partial to marked response ; several also showed relapses when placebo was substituted and improvement when carbamazepine was reinstituted . Five of 13 depressed patients showed significant improvement in depression ratings ; 3 additional patients experienced partial relapse when placebo was substituted . Carbamazepine might also have prophylactic as well as acute efficacy in patients with both phases of manic-depressive illness , including some patients who do not respond to lithium . Therapeutic effects were achieved with 600 - 1600 mg/day at blood levels of 8 - 12 microgram/ml with relatively few side effects . Carbamazepine may prove to be a useful additional treatment for affective illness", "OBJECTIVE Determine the efficacy and tolerability of olanzapine/fluoxetine combination ( OFC ) for treatment of acute bipolar I depression compared with lamotrigine . METHOD The 7-week , acute phase of a r and omized , double-blind study compared OFC ( 6/25 , 6/50 , 12/25 , or 12/50 mg/day ; N = 205 ) with lamotrigine ( [ LMG ] titrated to 200 mg/day ; N = 205 ) in patients with DSM-IV-diagnosed bipolar I disorder , depressed . The study was conducted from November 2003 to August 2004 . RESULTS Completion rates were similar between treatments ( OFC , 66.8 % vs. LMG , 65.4 % ; p = .835 ) . OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale ( primary outcome ) ( p = .002 , effect size = 0.26 ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) ( p = .002 , effect size = 0.24 ) , and Young Mania Rating Scale total scores ( p = .001 , effect size = 0.24 ) . Response rates did not significantly differ between groups when defined as > or = 50 % reduction in MADRS score ( OFC , 68.8 % vs. LMG , 59.7 % ; p = .073 ) . Time to response was significantly shorter for OFC-treated patients ( median days [ 95 % CI ] = OFC , 17 [ 14 to 22 ] vs. LMG , 23 [ 21 to 34 ] ; p = .010 ) . There was a significant difference in incidence of \" suicidal and self-injurious behavior \" adverse events ( OFC , 0.5 % vs. LMG , 3.4 % ; p = .037 ) . Somnolence , increased appetite , dry mouth , sedation , weight gain , and tremor occurred more frequently ( p OFC-treated patients than lamotrigine-treated patients . Weight , total cholesterol , and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients ( all p Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms , more treatment-emergent adverse events , greater weight gain , and some elevated metabolic factors with OFC than lamotrigine . Treatment differences were of modest size", "OBJECTIVE Antiepileptic drugs ( AEDs ) are commonly employed in the treatment of bipolar disorder . The efficacy and tolerability of topiramate , a novel anticonvulsant , and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions ( rater-blinded ) in patients meeting DSM-IV criteria for bipolar I/II depression . METHODS A total of 36 out- patients with Hamilton Depression Rating Scale ( HDRS-17 ) scores > or = 16 were r and omized to receive escalating doses of either topiramate ( 50 - 300 mg/day ) or bupropion SR ( 100 - 400 mg/day ) for 8 weeks . Data were analyzed on an intent-to-treat basis using the last observation carried forward method . RESULTS The percentage of patients meeting a priori response criteria ( > or = 50 % decrease from baseline in mean HDRS-17 total score ) was significant for both topiramate ( 56 % ) and bupropion SR ( 59 % ) [ t(17 ) = 2.542 , p = 0.04 and t(17 ) = 2.661 , p = 0.03 , respectively ] . Baseline demographic and clinical parameters were comparable between the two treatment groups . The mean doses of study medication were 176 mg/day ( SD = 102 mg/day ) for the topiramate-treated group and 250 mg/day ( SD = 133 mg/day ) for the bupropion SR-treated group . A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment , according to a > or = 50 % reduction in the HDRS-17 . Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups ( p = 0.001 ) , however , differences between the topiramate-treated group and the bupropion SR-treated group were not significant [ t(36 ) = 1.754 , p = 0.097 ] . Both topiramate and bupropion SR were generally well tolerated . Thirteen patients discontinued the study : 2 because of lack of efficacy , 1 due to withdrawal of consent and 10 following side-effects ( six in the topiramate and four in the bupropion SR-treated group ) . There were no cases of affective switch in either arm . Weight loss was experienced by patients in both groups ( mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate ) [ t(17 ) = 2.325 , p = 0.061 and t(17 ) = 2.481 , p = 0.043 , respectively ] . CONCLUSIONS These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression . The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation", "Chinese herbal medicines possess the therapeutic potential for mood disorders . This double-blind , r and omized , placebo-controlled study was design ed to evaluate the efficacy and side effects of the herbal medicine called Free and Easy W and erer Plus ( FEWP ) as an adjunct to carbamazepine ( CBZ ) in patients with bipolar disorders . One hundred and twenty-four bipolar depressed and 111 manic patients were r and omized to treatment with CBZ alone , CBZ plus FEWP , or equivalent placebo for 12 weeks . CBZ was initiated at 300mg/day and FEWP was given at a fixed dose of 36g/day . Efficacy measures included the Hamilton Rating Scale for Depression , Montgomery-Asberg Depression Rating Scale , Young Mania Rating Scale , Bech-Rafaelsen Mania Scale , and Clinical Global Impression-Severity ( CGI-S ) . CBZ monotherapy produced significantly greater improvement on manic measures at week 2 through endpoint and CGI-S of depression at endpoint compared to placebo . CBZ monotherapy also yielded significantly higher clinical response rates than placebo on bipolar depression ( 63.8 % vs. 34.8 % , p=0.044 ) and mania ( 87.8 % vs. 57.1 % , p=0.012 ) . Compared to CBZ monotherapy , adjunctive FEWP with CBZ result ed in significantly better outcomes on the three measures of depression at week 4 and week 8 and significantly greater clinical response rate in depressed subjects ( 84.8 % vs. 63.8 % , p=0.032 ) , but failed to produce significantly greater improvement on manic measures and the response rate in manic subjects . There was a lesser incidence of dizziness and fatigue in the combination therapy compared to CBZ monotherapy . These results suggest that adjunctive FEWP has additive beneficial effects in bipolar patients , particularly for those in depressive phase", "BACKGROUND This is the first prospect i ve longitudinal study , to our knowledge , of the natural history of the weekly symptomatic status of bipolar II disorder ( BP-II ) . METHODS Weekly affective symptom status ratings for 86 patients with BP-II were based on interviews conducted at 6- or 12-month intervals during a mean of 13.4 years of prospect i ve follow-up . Percentage of weeks at each symptom severity level and the number of shifts in symptom status and polarity were examined . Predictors of chronicity for BP-II were evaluated using new chronicity measures . Chronicity was also analyzed in relation to the percentage of follow-up weeks with different types of somatic treatment . RESULTS Patients with BP-II were symptomatic 53.9 % of all follow-up weeks : depressive symptoms ( 50.3 % of weeks ) dominated the course over hypomanic ( 1.3 % of weeks ) and cycling/mixed ( 2.3 % of weeks ) symptoms . Subsyndromal , minor depressive , and hypomanic symptoms combined were 3 times more common than major depressive symptoms . Longer intake episodes , a family history of affective disorders , and poor previous social functioning predicted greater chronicity . Prescribed somatic treatment did not correlate significantly with symptom chronicity . Patients with BP-II of brief ( 2 - 6 days ) vs longer ( > or = 7 days ) hypomanias were not significantly different on any measure . CONCLUSIONS The longitudinal symptomatic course of BP-II is chronic and is dominated by depressive rather than hypomanic or cycling/mixed symptoms . Symptom severity fluctuates frequently within the same patient over time , involving primarily symptoms of minor and subsyndromal severity . Longitudinally , BP-II is expressed as a dimensional illness involving the full severity range of depressive and hypomanic symptoms . Hypomania of long or short duration in BP-II seems to be part of the same disease process", "BACKGROUND Long-term outcomes are often poor in patients with bipolar disorder despite treatment ; more effective treatments are needed to reduce recurrences and morbidity . This study compared the efficacy of divalproex , lithium , and placebo as prophylactic therapy . METHODS A r and omized , double-blind , parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period . Patients who met the recovery criteria within 3 months of the onset of an index manic episode ( n = 372 ) were r and omized to maintenance treatment with divalproex , lithium , or placebo in a 2:1:1 ratio . Psychotropic medications were discontinued before r and omization , except for open-label divalproex or lithium , which were gradually tapered over the first 2 weeks of maintenance treatment . The primary outcome measure was time to recurrence of any mood episode . Secondary measures were time to a manic episode , time to a depressive episode , average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania , and Global Assessment of Function scores . RESULTS The divalproex group did not differ significantly from the placebo group in time to any mood episode . Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode . Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores . CONCLUSIONS The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy . Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures", "OBJECTIVE To study the efficacy of adjunctive levetiracetam therapy compared with placebo in the treatment of subjects with depression with bipolar disorder . METHOD This double-blind , placebo-controlled clinical trial r and omly assigned out patients with bipolar disorder type I and type II who were experiencing a major depressive episode ( Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version criteria ) to treatment with either placebo or adjunctive levetiracetam ( up to 2,500 mg/d flexibly dosed ) for 6 weeks . The subjects were recruited from October 2005 to June 2008 . The primary efficacy measure was mean change from baseline to week 6 in the Hamilton Depression Rating Scale ( 21-item ) . Secondary efficacy assessment s included the Montgomery-Åsberg Depression Rating Scale , the Beck Depression Inventory , the Clinical Global Impressions-Bipolar Version scale , the Hamilton Anxiety Rating Scale , and the Young Mania Rating Scale . RESULTS Of 42 subjects r and omly assigned to placebo or drug , 32 received at least 1 postbaseline assessment and thus were included in the analysis . The mean ( SD ) levetiracetam daily dose at endpoint evaluation was 1,132 ( 425 ) mg/d . There was no significant difference in the mean change from baseline to week 6 in the Hamilton Depression Rating Scale scores for levetiracetam compared with placebo . There were no significant differences in any of the secondary outcome measures . CONCLUSIONS Levetiracetam adjunctive therapy was not superior to placebo in the short-term treatment of subjects with depression with bipolar disorder in the population studied . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00566150", "Rationale Due to the episodic and chronic nature of bipolar disorder ( BD ) , maintenance therapy represents a critical part of treatment ; however , there is a paucity of studies comparing effectiveness of available long-term treatments . Objective The aim of this study is to determine and compare the efficacy of pharmacological treatments for maintenance treatment of BD by means of the number needed to treat ( NNT ) . Methods The efficacy of drugs used for maintenance treatment of BD , as emerging from the results of r and omized controlled trials , was assessed using the size effect measure of NNT . PubMed search es were conducted on English- language articles published until May 2010 using the search terms “ bipolar disorder , ” “ mania , ” “ mixed episode , ” or “ bipolar depression , ” cross-referenced with trial characteristic search phrases and generic names of medications . The search was supplemented by manually review ing reference lists from identified publications . Results In 15 studies , aripiprazole , olanzapine , quetiapine , risperidone long-acting injection , lithium , lamotrigine , and divalproex proved effectiveness in terms of NNTs ( ≥10 % advantage over placebo ) for prevention of relapse into any mood episode . Quetiapine , lithium , risperidone long-acting injection , aripiprazole , and olanzapine are effective in manic recurrence prevention . Lamotrigine , quetiapine , and lithium present significant NNTs for prevention of depressive relapses . Conclusions All of the pharmacological agents assessed were effective in the prevention of any kind of mood episode ; however , different efficacy profiles were found for prevention of manic and /or depressive relapses . The comparison of NNT values of the available agents may represent a useful tool in clinical setting s , in order to facilitate implementation of long-term pharmacological interventions in patients with BD", "OBJECTIVE Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines . The authors looked for the features associated with risk of recurrence . METHOD The authors examined prospect i ve data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) study for up to 24 months . For those who were symptomatic at study entry but subsequently achieved recovery , time to recurrence of mania , hypomania , mixed state , or a depressive episode was examined with Cox regression . RESULTS Of 1,469 participants symptomatic at study entry , 858 ( 58.4 % ) subsequently achieved recovery . During up to 2 years of follow-up , 416 ( 48.5 % ) of these individuals experienced recurrences , with more than twice as many developing depressive episodes ( 298 , 34.7 % ) as those who developed manic , hypomanic , or mixed episodes ( 118 , 13.8 % ) . The time until 25 % of the individuals experienced a depressive episode was 21.4 weeks and until 25 % experienced a manic/hypomanic/mixed episode was 85.0 weeks . Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence . Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic , hypomanic , or mixed episode recurrence . CONCLUSIONS Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery . Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence", "Breakthrough depression is a common problem in the treatment of bipolar disorder . Only one , recently published , double-blind , placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients . This report describes , in further detail , the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder . A r and omized , double-blind , parallel-group , multicenter study was conducted over a 52-week maintenance period . Bipolar I patients , who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode , were r and omized to maintenance treatment with divalproex , lithium , or placebo in a 2 : 1 : 1 ratio . Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase . Outcome measures were the rate of early discontinuation for depression , time to depressive relapse , proportion of patients with depressive relapse , mean change in Depressive Syndrome Scale score , proportion of patients receiving antidepressants , and time in the study . Among patients taking an antidepressant , a higher percentage of patients on placebo than divalproex discontinued early for depression . Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period . Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance . Indices of severity of pre study illness course predicted worse outcome in all treatment groups . Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder , particularly in patients who had responded to divalproex when manic , and among patients with a more severe course of illness", "Thirty-five depressed patients diagnosed by DSM-III criteria participated in a double-blind study of the acute antidepressant effects of the anticonvulsant carbamazepine , at average doses of 971 mg/day , achieving mean + /- SD blood levels of 9.3 + /- 1.9 micrograms/ml ( range , 3 - 12.5 micrograms/ml ) . Twenty patients ( 57 % ) showed at least mild improvement , and 12 showed more substantial improvement . Possible clinical predictors of antidepressant response to carbamazepine are discussed . These preliminary data suggest that carbamazepine has some acute antidepressant efficacy in addition to the growing evidence that it has acute antimanic and longer-term prophylactic efficacy in both phases of manic-depressive illness", "OBJECTIVE To conduct an exploratory evaluation of the acute efficacy of extended-release divalproex sodium compared to placebo in patients with bipolar I or II depression . METHOD Out patients aged 18 - 70 years with mood stabilizer-naive bipolar I or II disorder experiencing a major depressive episode ( DSM-IV ) were r and omly assigned to 6 weeks of divalproex sodium monotherapy or placebo . The primary outcome measure was mean change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) total score . Secondary outcomes included rates of response and remission , changes in the Clinical Global Impressions-Bipolar ( CGI-BP ) Severity of Illness scores , and changes in anxiety symptoms as measured by the Hamilton Anxiety Rating Scale . The study was conducted between 2003 and 2007 . RESULTS Fifty-four subjects with bipolar I ( n = 20 ) or bipolar II ( n = 34 ) disorder were r and omly assigned to divalproex or placebo ; 67 % ( 36 of 54 ) met DSM-IV criteria for rapid cycling . Divalproex treatment produced statistically significant improvement in MADRS scores compared with placebo from week 3 onward . The proportions of patients meeting response criteria were 38.5 % ( 10 of 26 ) in the divalproex group versus 10.7 % ( 3 of 28 ) for the placebo group ( P = .017 ) . The proportions of patients meeting remission criteria were 23.1 % ( 6 of 26 ) for divalproex versus 10.7 % ( 3 of 28 ) for placebo ( P = .208 ) . Subgroup analysis revealed no separation between divalproex and placebo for those with bipolar II diagnoses . Nausea , increased appetite , diarrhea , dry mouth , and cramps were the most common side effects . CONCLUSIONS These data suggest that divalproex sodium is efficacious and reasonably well tolerated in the acute treatment of mood stabilizer-naive patients with bipolar depression , particularly for those with rapid-cycling type I presentations , and that confirmatory large-scale studies are indicated . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00194116", "BACKGROUND The treatment of bipolar disorder in the depressed phase is complicated by a tendency for conventional antidepressant drugs to worsen the course of the illness by precipitating a manic episode or increasing cycle frequency . Thus , the potential antidepressant efficacy of mood stabilizers , such as divalproex , which is an effective treatment for the manic phase of bipolar disorder , is of considerable interest . METHODS The clinical efficacy of divalproex ( valproate , Depakote ) was tested in an 8-week , double-blind , placebo-controlled , r and omized clinical trial in 25 out patients with bipolar I depression . The primary outcome measure was the 17-item Hamilton Rating Scale for Depression , and secondary measures included the Hamilton Rating Scale for Anxiety , the Clinician Administered Rating Scale for Mania , and the Clinical Global Impression scale . RESULTS Using repeated measures ANOVA with last observation carried forward , divalproex was more effective than placebo in improving symptoms of depression ( p = 0.0002 ) and symptoms of anxiety ( p = 0.0001 ) than placebo . LIMITATIONS The sample size was small , and most patients were male . CONCLUSIONS These pilot results indicate that divalproex is effective in reducing the symptoms of depression and anxiety in bipolar I , depressed phase . These positive results support the need to perform a larger , multisite study of divalproex treatment for bipolar depression", "BACKGROUND More treatment options for bipolar depression are needed . Currently available antidepressants may increase the risk of mania and rapid cycling , and mood stabilizers appear to be less effective in treating depression than mania . Preliminary data suggest that lamotrigine , an established antiepileptic drug , may be effective for both the depression and mania associated with bipolar disorder . This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression . METHODS Out patients with bipolar I disorder experiencing a major depressive episode ( DSM-IV , N = 195 ) received lamotrigine ( 50 or 200 mg/day ) or placebo as monotherapy for 7 weeks . Psychiatric evaluations , including the Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , Mania Rating Scale , and the Clinical Global Impressions scale for Severity ( CGI-S ) and Improvement ( CGI-I ) were completed at each weekly visit . RESULTS Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D , HAM-D Item 1 , MADRS , CGI-S , and CGI-I compared with placebo . Improvements were seen as early as week 3 . Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures . The proportions of patients exhibiting a response on CGI-I were 51 % , 41 % , and 26 % for lamotrigine 200 mg/day , lamotrigine 50 mg/day , and placebo groups , respectively . Adverse events and other safety results were similar across treatment groups , except for a higher rate of headache in the lamotrigine groups . CONCLUSION Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression", "OBJECTIVE In two previous manuscripts , we described the efficacy of lamotrigine versus placebo as add-on to lithium ( followed by the addition of paroxetine in nonresponders ) in the short-term treatment of bipolar depression . In this paper we describe the long-term ( 68 weeks ) outcome of that study . METHODS A total of 124 bipolar depressed patients receiving lithium were r and omized to addition of lamotrigine or placebo . After eight weeks , paroxetine was added to nonresponders for another eight weeks . Responders continued medication and were followed for up to 68 weeks or until a relapse or recurrence of a depressive or manic episode . RESULTS After eight weeks , the addition of lamotrigine to lithium was significantly more efficacious than addition of placebo , while after addition of paroxetine in nonresponders both groups further improved with no significant difference between groups at week 16 . During follow-up the efficacy of lamotrigine was maintained : time to relapse or recurrence was longer for the lamotrigine group [ median time 10.0 months ( confidence interval : 1.1 - 18.8 ) ] versus the placebo group [ 3.5 months ( confidence interval : 0.7 - 7.0 ) ] . CONCLUSION In patients with bipolar depression , despite continued use of lithium , addition of lamotrigine revealed a continued benefit compared to placebo throughout the entire study", "BACKGROUND The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression . This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder . METHOD During an 8- to 16-week open-label phase , lamotrigine ( titrated to 200 mg/day ) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I out patients ( N = 966 ) and concomitant drugs were gradually withdrawn . Patients stabilized on open-label treatment ( N = 463 ) were then r and omly assigned to lamotrigine ( 50 , 200 , or 400 mg/day ; N = 221 ) , lithium ( 0.8 - 1.1 mEq/L ; N = 121 ) , or placebo ( N = 121 ) monotherapy for up to 18 months . The primary outcome measure was time from r and omization to intervention ( addition of pharmacotherapy ) for any mood episode ( depressive , manic , hypomanic , or mixed ) . Data were gathered from September 1997 to August 2001 . RESULTS Time to intervention for any mood episode was statistically superior ( p = .029 ) for both lamotrigine and lithium compared with placebo-median survival times were 200 , 170 , and 93 days , respectively . Intervention for depression was more frequent than for mania by a factor of nearly 3:1 . Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode ( p = .047 ) . The proportions of patients who were intervention-free for depression at 1 year were lamotrigine 57 % , lithium 46 % , and placebo 45 % . Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode ( p = .026 ) . The proportions of patients who were intervention-free for mania at 1 year were lamotrigine 77 % , lithium 86 % , and placebo 72 % . Headache was the most frequent adverse event for all 3 treatment groups . CONCLUSION Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients , with lamotrigine predominantly effective against depression and lithium predominantly effective against mania", "OBJECTIVE Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy . This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression . METHOD Out patients ( N = 124 ) aged 18 years and older with a DSM-IV bipolar I or II disorder and a major depressive episode ( Montgomery-Asberg Depression Rating Scale [ MADRS ] score > or = 18 and Clinical Global Impressions-Bipolar Version [ CGI-BP ] severity of depression score > or = 4 ) while receiving lithium treatment ( 0.6 - 1.2 mmol/L ) were r and omly assigned to 8 weeks of double-blind treatment with lamotrigine ( titrated to 200 mg/d ) or placebo . The primary outcome measure was mean change from baseline in total score on the MADRS at week 8 . Secondary outcome measures were response ( defined as a reduction of > or = 50 % on the MADRS and /or change of depression score on the CGI-BP of \" much improved \" or \" very much improved \" compared to baseline ) and switch to mania or hypomania ( defined as a CGI-BP severity of mania score of at least mildly ill at any visit ) . Patients were included in the study between August 2002 ( Spain started in October 2003 ) and May 2005 . RESULTS Endpoint mean change from baseline MADRS total score was -15.38 ( SE = 1.32 ) points for lamotrigine and -11.03 ( SE = 1.36 ) points for placebo ( t = -2.29 , df = 104 , p = .024 ) . Significantly more patients responded to lamotrigine than to placebo on the MADRS ( 51.6 % vs. 31.7 % , p = .030 ) , but not on the CGI-BP change of depression ( 64.1 % vs. 49.2 % , p = .105 ) . Switch to mania or hypomania occurred in 5 patients ( 7.8 % ) receiving lamotrigine and 2 patients ( 3.3 % ) receiving placebo ( p = .441 ) . CONCLUSION Lamotrigine was found effective and safe as add-on treatment to lithium in the acute treatment of bipolar depression . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00224510", "BACKGROUND Uncertainty exists regarding the best approach for treating bipolar depression among patients already receiving a first-line mood stabilizer . The aim of this pilot study was to compare adding a second mood stabilizer or an antidepressant at this treatment decision point . METHODS Twelve-week , r and omized , double-blind pilot trial comparing the addition of lamotrigine or citalopram for bipolar depressed patients on mood stabilizer medication . Change in depressive symptoms and risk of switch were examined . RESULTS Twenty subjects were r and omized . Each treatment group experienced a significant mean reduction in total MADRS scores ( citalopram Delta - 14.2 , p=0.002 ; lamotrigine Delta - 13.3 , p= 0.001 ) , and there was no significant difference between treatment groups ( p=0.78 ) . Total response rates increased from 31.6 % at week 6 to 52.6 % at week 12 . One out of ten patients in each group experienced a switch to hypomania . LIMITATIONS Small sample size . Lack of a placebo arm . CONCLUSIONS Results of this small trial suggest that both lamotrigine and citalopram appear to be reasonable choices as add-on acute treatment for bipolar depression , with response rates continuing to rise considerably past 6 weeks of treatment", "BACKGROUND Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers , relatively few controlled studies have examined treatment strategies for bipolar depression . OBJECTIVE To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression . DESIGN Double-blind , 8-week , r and omized controlled trial . SETTING Eighty-four sites ( inpatient and outpatient ) in 13 countries . Patients A total of 833 r and omized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score of at least 20 . Intervention Patients were r and omly assigned to receive placebo ( n = 377 ) ; olanzapine , 5 to 20 mg/d ( n = 370 ) ; or olanzapine-fluoxetine combination , 6 and 25 , 6 and 50 , or 12 and 50 mg/d ( n = 86 ) . MAIN OUTCOME MEASURE Changes in MADRS total scores using mixed-effects model repeated- measures analyses . RESULTS During all 8 study weeks , the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group ( P olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8 . At week 8 , MADRS total scores were lower than at baseline by 11.9 , 15.0 , and 18.5 points in the placebo , olanzapine , and olanzapine-fluoxetine groups , respectively . Remission criteria were met by 24.5 % ( 87/355 ) of the placebo group , 32.8 % ( 115/351 ) of the olanzapine group , and 48.8 % ( 40/82 ) of the olanzapine-fluoxetine group . Treatment-emergent mania ( Young Mania Rating Scale score or = 15 subsequently ) did not differ among groups ( placebo , 6.7 % [ 23/345 ] ; olanzapine , 5.7 % [ 19/335 ] ; and olanzapine-fluoxetine , 6.4 % [ 5/78 ] ) . Adverse events for olanzapine-fluoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea . CONCLUSIONS Olanzapine is more effective than placebo , and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms", "OBJECTIVES The efficacy of lamotrigine as maintenance treatment for bipolar disorder ( BD ) , particularly for delaying depressive episodes , is well established , but its efficacy in the acute treatment of bipolar depression is less clear . This paper reports the results of five r and omized , double-blind , placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression . METHODS Adult subjects with bipolar I or II disorder experiencing a depressive episode were r and omized to placebo or lamotrigine monotherapy ( after titration , at a fixed dose of 50 mg or 200 mg daily in Study 1 ; a flexible dose of 100 - 400 mg daily in Study 2 ; or a fixed dose of 200 mg daily in Studies 3 , 4 and 5 ) for 7 - 10 weeks . RESULTS Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [ 17-item Hamilton Depression Rating Scale in Studies 1 and 2 ; Montgomery-Asberg Depression Rating Scale ( MADRS ) in Studies 3 , 4 and 5 ] . In Study 1 , lamotrigine significantly separated from placebo on some secondary measures of efficacy , including the MADRS , the Clinical Global Impressions-Severity ( CGI-S ) and the CGI-Improvement ( CGI-I ) , but seldom differed on secondary efficacy endpoints for the other studies . CONCLUSIONS Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies . Lamotrigine was well tolerated in the acute treatment of bipolar depression" ]

[ "Cassia tora fiber supplement consisting of 2 g of soluble fiber extracted from Cassia semen ( C. tora L. ) , 200 mg of alpha-tocopherol , 500 mg of ascorbic acid , and 300 mg of maltodextrin was formulated in a pack , and given to 15 type II diabetic subjects ( seven men and eight women 57.1 + /- 2.9 years old ) with instructions to take two packs per day for 2 months . Placebo contained maltodextrin only with a little brown caramel color . Lifestyle factors and dietary intakes of the subjects were not altered during the 2-month period . Serum total cholesterol was moderately ( P C. tora group compared with the age- and gender-matched placebo group , as was the ratio of apolipoprotein B to apolipoprotein A1 ( P Levels of serum triglycerides and low-density lipoprotein-cholesterol tended to decrease more in the C. tora-supplemented group than in the placebo group . Serum alpha-tocopherol was increased ( P lipid peroxides were not significantly lower in the C. tora group . Fasting blood glucose , hemoglobin A1c , blood urea nitrogen , creatinine , and activities of serum aspartate aminotransferase and alanine aminotransferase were not changed by the fiber supplement . We concluded that C. tora supplements can help improve serum lipid status in type II diabetic subjects without serious adverse effects", "Background : To reach fetal appropriate growth during the third trimester , the requirements for dietary calcium and iron intakes during the pregnancy increases . This study was carried out to determine the effects of daily consumption of probiotic yoghurt on serum calcium and iron levels and liver enzymes among Iranian healthy pregnant women . Methods : In this controlled clinical trial , 70 primigravida pregnant women carrying singleton pregnancy at their third trimester were participated . Participants were r and omly divided into two groups of consuming 200 g/d of conventional ( n = 33 ) or probiotic yogurts ( n = 37 ) for 9 weeks . The probiotic yogurt contained Lactobacillus acidophilus and Bifidobacterium lactis with a total of min 1 × 107 CFU . To measure serum calcium , iron , aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) levels , blood sample s were drawn in a fasting state at baseline and after 9 weeks intervention . Results : Consumption of probiotic yogurt result ed in maintaining serum calcium levels compared with the conventional yogurt ( P = 0.01 ) . Within-group differences in the conventional yogurt group revealed a significant reduction of serum calcium levels ( −1.7 mg/dL , P effects on serum iron , AST and ALT levels . Conclusions : Consumption of probiotic yogurt among pregnant women result ed in maintaining serum calcium levels compared with the conventional yogurt ; however , it could not affect serum iron , ALT and AST levels ", "This study aim ed to evaluate the relationship between gut probiotic flora and nonalcoholic fatty liver disease in a diet-induced rat model , and to compare the effects of two different probiotic strains on nonalcoholic fatty liver disease . Forty male Sprague-Dawley rats were r and omized into 4 groups for 12 weeks : control ( st and ard rat chow ) , model ( fat-rich diet ) , Lactobacillus ( fat-rich diet plus Lactobacillus acidophilus ) , and Bifidobacterium ( fat-rich diet plus Bifidobacterium longum ) groups . Probiotics were provided to rats in drinking water ( 1010/ml ) . Gut bifidobacteria and lactobacilli were obviously lower at weeks 8 and 10 , respectively , in the model group compared with the control group . Supplementation with Bifidobacterium significantly attenuated hepatic fat accumulation ( 0.10 ± 0.03 g/g liver tissue ) compared with the model group ( 0.16 ± 0.03 g/g liver tissue ) . However , there was no improvement in intestinal permeability in either the Lactobacillus or the Bifidobacterium group compared with the model group . In all 40 rats , the hepatic total lipid content was negatively correlated with gut Lactobacillus ( r = −0.623 , p = 0.004 ) and Bifidobacterium ( r = −0.591 , p = 0.008 ) . Oral supplementation with probiotics attenuates hepatic fat accumulation . Further , Bifidobacterium longum is superior in terms of attenuating liver fat accumulation than is Lactobacillus acidophilus", "Background The beneficial effect of probiotics on renal profile and liver function has been reported among patients with chronic kidney disease and fatty liver respectively . However , its effect on renal profile and liver function among type 2 diabetic individuals has not been fully understood . To investigate the effect of microbial cell preparation on renal profile and liver function tests among type 2 diabetic individuals . Methods A r and omized , double-blind , parallel-group , controlled clinical trial was conducted on a total of 136 type 2 diabetics age 30 - 70 years old in a teaching hospital in Kuala Lumpur , Malaysia . Subjects were r and omly assigned to receive microbial cell preparation ( N = 68 ) or a placebo ( N = 68 ) for 12 weeks . The outcomes measured at baseline , week 6 , and week 12 and included changes in renal profile ( Sodium , Potassium , Urea , Creatinine , Glomerular Filtration Rate ) , and liver function tests ( Albumin , Total Protein , Alkaline Phosphatase , Alanine Aminotransferase , Aspartate Aminotransferase ) . Intention to treat ( ITT ) analysis was performed on all the recruited subjects , while per protocol ( PP ) analysis was conducted on those who completed the trial with good compliance . Result The urea levels significantly declined in the probiotic group . Serum urea levels reduced from 4.26 mmol/L to 4.04 mmol/L in Probiotic Group while it increased in Placebo Group from 4.03 mmol/L to 4.24 mmol/L. These changes were significant between groups in ITT analysis ( p = 0.018 ) . Other parameters did not change significantly between groups . Conclusion 12 weeks supplementation with daily dosage of 6 × 1010 Colony Forming Units of multi-strain microbial cell preparation significantly improved urea levels . Trial registration ( Clinical trials : # NCT01752803", "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", "BACKGROUND S AND AIMS Type 2 diabetic mellitus ( T2DM ) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities . In the current study we aim ed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes , serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM . METHODS Forty-six diabetic females patients were r and omly allocated into intervention ( n=27 ) and control ( n=22 ) groups . Subjects in the intervention group received a daily dose of 10 g of chicory and subjects in control group received a placebo for two months . Anthropometric variables , glucose homeostasis , hematological parameters and metabolic indices including serum alanine aminotransfersae ( ALT ) , aspartate aminotransferase ( AST ) , alkaline phosphatase ( ALP ) , calcium and phosphorous as well as creatinine concentrations , glomerular filtration rate ( GFR ) and blood pressure were assessed at the beginning and end of the trial . RESULTS Significant reductions in fasting serum glucose ( FSG ) , Hb A1C , AST and ALP concentrations were observed in chicory-treated group . Systolic and diastolic blood pressures were also reduced in chicory-treated group . Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred ( P=0.014 ) . Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume ( MCV ) values ( P in serum insulin , creatinine and GFR were not significant . CONCLUSION The present study showed beneficial effects of oligofructose-enriched chicory on the improvement of the glucose and calcium homeostasis , liver function tests , blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM . Further studies in both genders are needed to generalize these findings to total population", "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 ", "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", "Background : This research was to examine the effects of synbiotic intake on minerals , liver enzymes , and blood pressure in patients with type 2 diabetes ( T2D ) . Methods : This r and omized , cross-over clinical trial was performed among 62 diabetic patients . Persons were r and omly assigned to intake either a synbiotic ( n = 62 ) or a control food ( n = 62 ) for 6 weeks . A 3-week washout period was applied following which persons were crossed over to the alternate intervention arm for an additional 6 weeks . The synbiotic was consisted of Lactobacillus sporogenes ( 1 × 107 CFU ) , 0.04 g inulin ( HPX ) as prebiotic . Persons were asked to consume the synbiotic and control foods 27 g a day . Blood pressure was measured , and blood sample s were taken at baseline and after 6-week intervention to assess calcium , magnesium , iron , alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase , and total bilirubin . Results : The consumption of a synbiotic food , compared to the control food , result ed in a significant rise of calcium ( 0.66 vs. −0.14 mg/dL , P = 0.03 ) and iron ( 5.06 vs. −9.98 mg/dL , P = 0.03 ) . The decrease of total bilirubin ( 0.08 vs. −0.04 mg/dL ; P = 0.009 ) was also seen in the synbiotic group compared with the control group . Conclusions : Overall , synbiotic in T2D patients had beneficial effects on calcium , iron , and total bilirubin concentrations ", "The purpose of this study was to evaluate the effect of xylooligosaccharide ( XOS ) on the blood sugar , lipids and oxidative status in type 2 diabetes mellitus ( DM ) . A total of 26 outpatient subjects of Taichung Veterans General Hospital , Taiwan , with HbA1c levels between 7.0 and 10.0 % and triglyceride were enrolled in the present study . Subjects were supplemented with 4 g/d XOS ( n=12 ) or a placebo ( n=14 ) for 8 wk in a r and omized double-blind clinical design . The results showed that the anthropometric values and nutrient intakes did not change during the experimental period . XOS supplementation not only reduced the glucose , HbA1c and fructosamine concentrations , but also decreased the levels of total cholesterol , low density lipoprotein ( LDL ) cholesterol , oxidized low density lipoprotein ( ox-LDL ) and apolipoprotein B. The activity of catalase of the erythrocyte sample decreased in the XOS group , but not the activities of superoxide dismutase and glutathione peroxidase . In conclusion , the dietary supplementation with XOS for 8 wk was effective in improving the blood sugar and lipids in type 2 diabetes , indicating that XOS-containing diets might be beneficial to DM subjects", "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", "Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease ( NAFLD ) . But it remains unknown in nonobese NAFLD . This prospect i ve , cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression . A total of 126 nonobese subjects were enrolled : 43 NAFLD and 83 healthy controls ( HC ) . The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region . Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD . Compared with HC , patients had 20 % more phylum Bacteroidetes ( p = 0.005 ) and 24 % less Firmicutes ( p = 0.002 ) . Within Firmicutes , four families and their 8 genera , which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria , were significantly decreased . Moreover , Gram-negative ( G− ) bacteria were prevalent in NAFLD ( p = 0.008 ) . Furthermore , a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD . This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression", "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 Non-alcoholic fatty liver disease ( NAFLD ) is becoming a public health problem worldwide and using microalgae is a new approach on its treatment . The aim of this study was to investigate the effect of Chlorella vulgaris supplementation on liver enzymes , serum glucose and lipid profile in patients with NAFLD . METHODS This double-blind r and omized placebo-controlled clinical trial was conducted on 60 NAFLD patients from specialized clinics of Tabriz University of Medical Sciences from December 2011 to July 2012 . The subjects were r and omly allocated into 2 groups : 1 ) \" intervention \" ( n=30 ) received 400 mg/day vitamin E plus four 300 mg tablets of Chlorella vulgaris and , 2 ) \" placebo \" ( n=30 ) received 400 mg/day vitamin E and four placebo tablets per day for 8 weeks . Weight , liver enzymes and metabolic factors were assessed in fasting serum and dietary data was collected at baseline and end of the study . RESULTS Weight , liver enzymes , fasting blood sugar ( FBS ) and lipid profile decreased significantly in both groups ( P differences in weight , ALP and FBS between the two groups were statistically significant ( P=0.01 , P=0.04 and P=0.02 , respectively ) . CONCLUSION C. vulgaris seems to improve FBS and lipid profile and therefore could be considered as an effective complementary treatment in NAFLD", "Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease . Our recent report suggested that oat , rich in beta-glucan , had a metabolic-regulating and liver-protecting effect in an animal model . In this study , we performed a clinical trial to further confirm the effect of oat . Subjects with BMI ≧27 and aged 18–65 , were r and omly divided into a control ( n = 18 ) and an oat-treated ( n = 16 ) group , taking a placebo or beta glucan-containing oat cereal , respectively , for 12 weeks . Our data showed that consumption of oat reduced body weight , BMI , body fat and the waist-to-hip ratio . Profiles of hepatic function , including AST , but especially ALT , were useful re sources to help in the evaluation of the liver , since both showed decrements in patients with oat consumption . Nevertheless , anatomic changes were still not observed by ultrasonic image analysis . Ingestion of oat was well tolerated and there was no adverse effect during the trial . In conclusion , consumption of oat reduced obesity , abdominal fat , and improved lipid profiles and liver functions . Taken as a daily supplement , oat could act as an adjuvant therapy for metabolic disorders", "Fecal microbiota transplantation ( FMT ) has evolved from a case report in the medical literature to the basis of major innovations in the treatment of Clostridium difficile infection ( CDI ) and , potentially , inflammatory bowel disease ( IBD ) . In the clinical setting , FMT was noted to significantly lower the risk of recurrent CDI , likely by increasing microbial diversity and altering the metabolic environment in the intestinal tract of recipients . In parallel , advances in the ability to quantify and characterize microbial communities in fecal sample s led to the association of IBD with a state of intestinal dysbiosis . Consequently , a number of case series and r and omized , controlled trials have evaluated FMT in treating active ulcerative colitis or Crohn 's disease . Unlike in CDI , the efficacy of FMT in the treatment of IBD appears to be influenced by a number of factors , including donor microbial profiles , inflammatory burden , and the microbial diversity of the recipient . The therapeutic potential of the microbiome has led to a number of biotechnology and pharmaceutical companies isolating specific strains from healthy stool for use as targeted therapies for IBD in clinical trials . Ongoing studies are likely to determine the missing link between the efficacy of FMT and its impact on microbial communities and mucosal inflammation", "The effects of chronic alcohol consumption on the bowel flora and the potential therapeutic role of probiotics in alcohol-induced liver injury have not previously been evaluated . In this study , 66 adult Russian males admitted to a psychiatric hospital with a diagnosis of alcoholic psychosis were enrolled in a prospect i ve , r and omized , clinical trial to study the effects of alcohol and probiotics on the bowel flora and alcohol-induced liver injury . Patients were r and omized to receive 5 days of Bifidobacterium bifidum and Lactobacillus plantarum 8PA3 versus st and ard therapy alone ( abstinence plus vitamins ) . Stool cultures and liver enzymes were performed at baseline and again after therapy . Results were compared between groups and with 24 healthy , matched controls who did not consume alcohol . Compared to healthy controls , alcoholic patients had significantly reduced numbers of bifidobacteria ( 6.3 vs. 7.5 log colony-forming unit [CFU]/g ) , lactobacilli ( 3.15 vs. 4.59 log CFU/g ) , and enterococci ( 4.43 vs. 5.5 log CFU/g ) . The mean baseline alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , and gamma-glutamyl transpeptidase ( GGT ) activities were significantly elevated in the alcoholic group compared to the healthy control group ( AST : 104.1 vs. 29.15 U/L ; ALT : 50.49 vs. 22.96 U/L ; GGT 161.5 vs. 51.88 U/L ) , indicating that these patients did have mild alcohol-induced liver injury . After 5 days of probiotic therapy , alcoholic patients had significantly increased numbers of both bifidobacteria ( 7.9 vs. 6.81 log CFU/g ) and lactobacilli ( 4.2 vs. 3.2 log CFU/g ) compared to the st and ard therapy arm . Despite similar values at study initiation , patients treated with probiotics had significantly lower AST and ALT activity at the end of treatment than those treated with st and ard therapy alone ( AST : 54.67 vs. 76.43 U/L ; ALT 36.69 vs. 51.26 U/L ) . In a subgroup of 26 subjects with well-characterized mild alcoholic hepatitis ( defined as AST and ALT greater than 30 U/L with AST-to-ALT ratio greater than one ) , probiotic therapy was associated with a significant end of treatment reduction in ALT , AST , GGT , lactate dehydrogenase , and total bilirubin . In this subgroup , there was a significant end of treatment mean ALT reduction in the probiotic arm versus the st and ard therapy arm . In conclusion , patients with alcohol-induced liver injury have altered bowel flora compared to healthy controls . Short-term oral supplementation with B. bifidum and L. plantarum 8PA3 was associated with restoration of the bowel flora and greater improvement in alcohol-induced liver injury than st and ard therapy alone", "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", "The pilot study evaluated the efficiency of oral soluble fibers to treat patients with nonalcoholic fatty liver disease . Twelve patients received 10 g/day of soluble fibers during 3 months . After the treatment 100 % of patients presented reduction in body mass index , waist circumference and insulin resistance index . In 66.7 % of the patients were observed reduction of the cholesterol levels and 75 % presented normal liver enzymes ( AST , ALT , and GGT ) . The present study suggests that oral soluble fibers may be useful to control risk factors and liver enzymes in patients with nonalcoholic fatty liver disease . However , future studies with histological controls are considered necessary", "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", "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 Hepatic encephalopathy ( HE ) is a reversible neuropsychiatric syndrome in patients with liver disease . It was suggested that Bifidobacterium+fructo-oligosaccharides ( FOS ) may decrease blood and brain ammonia levels . Aim The study was conducted to compare the efficacy of Bifidobacterium+FOS and lactulose in patients with HE . Methods One hundred and twenty-five patients ( 35 hepatitis B virus infected , 70 hepatitis C virus infected and 20 cryptogenetic cirrhosis ) were enrolled in the study . Patients were r and omized either to a treatment for 60 days with Bifidobacterium and FOS ( group A ) or into-group receiving lactulose ( group B ) in double-blind . Results After 30 days of the study period , the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of Trail Making Test B ( TMT B ) ( P Symbol Digit Modalities Test ( P Block Design Test ( P Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of NH4 fasting HE1 ( P TMT A ( P TMT B ( P Symbol Digit Modalities Test ( P Block Design Test ( P Bifidobacterium+FOS is an alternative to the use of lactulose in patients with cirrhosis , for its usefulness in reducing blood ammonia levels and improvement of psychometric tests", "Abstract We evaluated the effects of koumiss on some hematological and biochemical characteristics of persons who exercise . Eighteen sedentary males were assigned to three equal groups : koumiss ( K ) , koumiss + exercise ( KE ) and exercise alone ( E ) . Leukocytes ( WBC ) , differential leucocyte count , erythrocytes ( RBC ) , hemoglobin ( HGB ) , hematocrit ( HCT ) , platelet ( PLT ) , glucose , total cholesterol , triglycerides , high density lipoprotein ( HDL ) , aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) were assessed In blood sample s. By the end of the study , triglycerides ( TG ) and cholesterol levels tended to decrease in all groups , but the decrease was significant only at day 15 for the KE group . HDL tended to be increased in all groups at day 15 , but the increase was significant only in the KE group . We found that koumiss had beneficial effects on some hematological and biochemical characteristics", "Nonalcoholic fatty liver disease ( NAFLD ) is the most common form of chronic liver disease in the pediatric population . Preliminary evidence suggests a potential therapeutic utility of probiotics for this condition . Here , we tested the potential effect of the probiotic VSL#3 ( a multistrain preparation composed of Streptococcus thermophilus and several species of Lactobacillus and Bifidobacteria ) on oxidative and inflammatory damage induced by a high-fat diet in the liver of young rats . At weaning , young male Sprague-Dawley rats were r and omly divided into 3 groups ( n = 6 ) fed a st and ard , nonpurified diet ( Std ; 5.5 % of energy from fat ) or a high-fat liquid diet ( HFD ; 71 % of energy from fat ) . One of the HFD groups received by gavage VSL#3 ( 13 x 10(9 ) bacteria x kg(-1 ) x d(-1 ) ) . After 4 wk , the HFD rats had greater body weight gain , fat mass , serum aminotransferase , and liver weight than rats fed the Std diet . The HFD induced liver lipid peroxidation , tumor necrosis factor ( TNFalpha ) production , protein S-nitrosylation , inducible nitric oxide synthase ( iNOS ) , cyclooxygenase (COX)-2 expression , and metalloproteinase ( MMP ) activity . Moreover , in the HFD group , PPARalpha expression was less than in rats fed the Std diet . In rats fed the HFD diet and treated with VSL#3 , liver TNFalpha levels , MMP-2 and MMP-9 activities , and expression of iNOS and COX-2 were significantly lower than in the HFD group . In VSL#3-treated rats , PPARalpha expression was greater than in the HFD group . A modulation of the nuclear factor-kappaB pathway by VSL#3 was also demonstrated . Our data suggest that VSL#3 administration could limit oxidative and inflammatory liver damage in patients with NAFLD" ]

[ "Objectives . The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation . Although the factors that contribute to the development of type 2 diabetes are complex and not wholly eluci date d , the triad of severe obesity , hyperinsulinemia , and a family history of type 2 diabetes places a child at an increased risk for development of the disease . Current approaches to the prevention of type 2 diabetes , including dietary counseling and exercise , have had limited success . We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients . To that end , we conducted a double-blind , placebo-controlled study of the effects of metformin on body mass index ( BMI ) , serum leptin , glucose tolerance , and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes . Methods . The study population consisted of 29 white and black adolescents aged 12 to 19 years . All had BMI s exceeding 30 kg/m2 . Criteria for enrollment included : 1 ) a fasting insulin concentration exceeding 15 μU/mL ; and 2 ) at least 1 first- or second-degree relative with type 2 diabetes . All patients had fasting plasma glucose concentrations hirsutism , severe acne , or menstrual irregularities characteristic of polycystic ovary syndrome . Eight participants had acanthosis nigricans . After baseline laboratory studies including a rapidly sample d intravenous glucose tolerance test , patients were r and omized to receive metformin ( 500 mg twice daily ) or a placebo for a total of 6 months . The effects of metformin on BMI st and ard deviation score , serum leptin , glucose tolerance , and serum lipids were analyzed . The study was double-blinded and included no specific dietary restrictions . Results . Metformin caused a decline of 0.12 st and ard deviation in BMI in study participants ( −1.3 % from baseline ) , and a 5.5 % reduction in serum leptin in girls . In contrast , BMI and serum leptin rose 0.23 st and ard deviation ( 2.3 % ) and 16.2 % , respectively , in the placebo group during the treatment period . Metformin caused a progressive decline in fasting blood glucose ( from a mean of 84.9 to 75.1 mg% ) and a reduction in fasting insulin levels ( from 31.3 to 19.3 μU/mL ) . In contrast , fasting glucose levels in the placebo group rose slightly from 77.2 to 82.3 mg% , and fasting insulin levels did not change . Insulin sensitivity , as assessed by the ratio of fasting insulin to glucose concentrations and the quantitative insulin sensitivity check index ( 1/[log fasting insulin + log fasting glucose ] ) and homeostasis model assessment insulin resistance index ( fasting insulin × fasting glucose/22.5 ) indices , increased slightly in the metformin-treated participants . However , the insulin sensitivity measured using Bergman 's minimal model did not change . There were also no significant changes in glucose effectiveness , hemoglobin A1c , serum lipids , or serum lactate in the metformin or placebo groups . Metformin was tolerated well by the majority of patients . Transient abdominal discomfort or diarrhea occurred in 40 % of treated participants ; there were no episodes of vomiting or lactic acidosis . Conclusions . The treatment of obesity and insulin resistance in adults often proves ineffective because the vicious cycle leading to type 2 diabetes may have become entrenched and , to some extent , may be irreversible . Early detection and therapy of the obese adolescent with a family history of type 2 diabetes may interrupt the cycle of weight gain and insulin resistance that leads to glucose intolerance in adulthood . Through its ability to reduce fasting blood glucose and insulin concentrations and to moderate weight gain , metformin might complement the effects of dietary and exercise counseling and reduce the risk of type 2 diabetes in selected patients", "OBJECTIVE The management of obesity , apart from exercise , mainly involves a calorie restriction regimen . A pharmaceutical treatment is often used to improve patient compliance and diet effectiveness , although several side-effects have previously been described . To improve patient compliance and diet effectiveness without incurring unpleasant side-effects , we evaluated whether a distracting mini-meal can physiologically decrease the absorption of fats and carbohydrates . DESIGN Two minutes before each of the three meals consumed daily , 32 obese patients were treated with a distracting mini-meal , 32 with metformin , and 32 with placebo . At baseline and after 1 , 3 , and 6 months of treatment , body weight , body mass index , waist circumference , fasting/post-pr and ial insulinaemia and glycaemia , homeostasis model assessment -index , triacylglycerols , and total cholesterol were evaluated . RESULTS All patients showed good compliance . With the exception of post-pr and ial glycaemia , a significant reduction in all parameters was documented in every group , albeit the greater variation was observed in patients treated with a distracting mini-meal or metformin . No one showed noteworthy side-effects . CONCLUSIONS Our study focuses on a distracting mini-meal that could become a useful tool in enhancing weight loss . The beneficial effect of a distracting meal on insulin resistance , glucose , and lipid metabolism suggest its possible use to prevent or mitigate obesity-related disorders", "Objectives : Obesity and hypertension are associated with an adverse metabolic profile and systemic low- grade inflammation . Metformin reduces weight and inflammation in patients with diabetes , but it is unclear whether it has beneficial effects in patients without diabetes . The objective was to explore whether metformin-based treatment could benefit obesity-related hypertension without diabetes . Methods : A r and omized , double-blind , placebo-controlled factorial trial was conducted in 360 obese hypertensive patients without diabetes in Chongqing , China . After a 1–2-week run-in period , patients were r and omly assigned to metformin ( 500 mg once per day ) or placebo , as well as to an antihypertensive medication . Change in blood pressure , obesity measurements and metabolic profile were assessed at 24 weeks . Results : The 180 participants r and omized to metformin and 180 r and omized to placebo were similar at baseline . At 24 weeks , metformin compared with placebo did not have significant effects on blood pressure , blood glucose , high-density or low-density lipoprotein cholesterol , but it did reduce total serum cholesterol ( 0.27mmol/l , P = 0.038 ) . Metformin also significantly reduced weight ( −0.7 kg , P = 0.006 ) , BMI ( −0.2 kg/m2 , P = 0.024 ) , waist circumference ( −0.9 cm , P = 0.008 ) , and both subcutaneous ( −6.1 cm2 , P = 0.043 ) and visceral adiposity ( −5.4 cm2 , P = 0.028 ) as measured by computed tomography , and lowered serum high-sensitivity C-reactive protein levels ( −0.6 mg/dl , P in adverse events ( P = 0.785 ) . Conclusions : Metformin has no effect on blood pressure and blood glucose levels , but it does reduce total cholesterol , abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes", "This study assessed the efficacy of adding metformin to a structured lifestyle intervention in reducing BMI in obese adolescents with insulin resistance . Obese adolescents ( 25 ) aged 10–16 years with a body mass index ( BMI ) > 95th percentile and insulin resistance ( Homeostasis Model Assessment —HOMA ) > 3.0 were assessed in a community clinic . A structured lifestyle intervention comprising nutritional and exercise education and motivational support in both individual and group sessions was delivered over 6 months . Subjects were r and omized to lifestyle intervention alone or with metformin ( 1500 g daily ) . The primary outcome measures were a change in BMI and modification of metabolic risk factors , including insulin resistance , plasma lipids and adipocytokines . Eleven adolescents receiving lifestyle and metformin intervention and 14 receiving lifestyle alone completed the study . BMI decreased by 1.8 kg/m2 with lifestyle and metformin but did not change with lifestyle alone . HOMA was significantly decreased in the lifestyle intervention group , but not following metformin , while the adiponectin/leptin ratio improved significantly in both groups . Dyslipidemic profiles improved most significantly with metformin . We conclude that metformin in combination with a 6-month structured lifestyle intervention is effective in reducing BMI in obese adolescents but did not improve insulin resistance . Lifestyle intervention , with or without metformin , improved metabolic risk factors such as plasma lipids and adipocytokines ", "Objective : To study the long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance . Patients : 181 African American subjects with insulin resistance and normal glucose tolerance test were r and omised to receive glipizide 5 mg/day ( n = 25 ) , metformin 500 mg/day ( n = 59 ) , or placebo ( n = 97 ) for 24 months . Insulin sensitivity , glucose tolerance , lipid profile , left ventricular mass ( echocardiography ) , aortic distensibility ( echocardiography , blood pressure ) , aortic pulse wave velocity ( PWV , carotid to femoral artery , Doppler ) were measured at baseline and at 12 and 24 months after r and omisation . Results : A significant increase in PWV was observed in both glipizide ( mean ( SEM ) change at 24 months 2.8 ( 2.7 ) m/s , p = 0.012 ) and metformin ( 2.2 ( 0.7 ) m/s , p = 0.01 ) groups during the follow up period . In contrast , PWV remained unchanged in the placebo group . The increase in PWV in the treatment groups was significant compared with placebo ( analysis of variance p cardiovascular or metabolic variables did not change significantly compared with placebo during follow up . Conclusions : The observed increase in PWV is consistent with a decrease in the elastic properties of the aorta . The use of oral antidiabetic agents for the prevention of cardiovascular complications in non-diabetic African Americans with insulin resistance needs to be critically evaluated", "Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo ) . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo . Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo . Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin . SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo . Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED", "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", "OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions , including abnormalities in glucose homeostasis in adolescents , but there are few data evaluating the efficacy of metformin among younger children . Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children , who are insulin-resistant . RESEARCH DESIGN AND METHODS This study was a r and omized double-blind placebo-controlled trial consisting of 100 severely obese ( mean BMI 34.6 ± 6.6 kg/m2 ) insulin-resistant children aged 6–12 years , r and omized to 1,000 mg metformin ( n = 53 ) or placebo ( n = 47 ) twice daily for 6 months , followed by open-label metformin treatment for 6 months . All children and their parents participated in a monthly dietitian-administered weight-reduction program . RESULTS Eighty-five percent completed the 6-month r and omized phase . Children prescribed metformin had significantly greater decreases in BMI ( difference −1.09 kg/m2 , CI −1.87 to −0.31 , P = 0.006 ) , body weight ( difference −3.38 kg , CI −5.2 to −1.57 , P ( difference between metformin and placebo groups −0.07 , CI −0.12 to −0.01 , P = 0.02 ) , and fat mass ( difference −1.40 kg , CI −2.74 to −0.06 , P = 0.04 ) . Fasting plasma glucose ( P = 0.007 ) and homeostasis model assessment ( HOMA ) insulin resistance index ( P = 0.006 ) also improved more in metformin-treated children than in placebo-treated children . Gastrointestinal symptoms were significantly more prevalent in metformin-treated children , which limited maximal tolerated dosage in 17 % . During the 6-month open-label phase , children treated previously with placebo decreased their BMI Z score ; those treated continuously with metformin did not significantly change BMI Z score further . CONCLUSIONS Metformin had modest but favorable effects on body weight , body composition , and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program", "AIMS This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations . METHODS Nineteen obese patients with impaired glucose tolerance ( IGT ) were treated with either metformin or placebo in a r and omized , double-blind , placebo-controlled , cross-over study . Insulin secretion and insulin resistance were quantified using the homeostasis model assessment ( HOMA ) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose ( SSPG ) . RESULTS The average benefit of metformin was 0.6 mmol/l for glucose ( 95 % confidence interval ( CI ) 0.2 - 0.9 P = 0.002 ) , 2.8 pmol/l for insulin ( 95 % CI 0.2 - 5.4 , P = 0.019 ) . Insulin resistance , as quantified by HOMA , was improved by 1.1 ( 95 % CI 0.2 - 2.0 , P = 0.004 ) , without any change in insulin secretion . Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period , as was the SSPG concentration . However , both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo . CONCLUSIONS These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure . In contrast , neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia", "BACKGROUND In the BIGPRO 1 trial , one year of treatment with metformin in non-diabetic obese subjects with a central fat distribution had no significant effect on fasting plasma triglyceride concentration or on blood pressure despite a decrease in weight , fasting plasma insulin and glucose concentrations . To re-evaluate the effect of metformin on fasting triglyceride concentration and on blood pressure , the BIGPRO 1.2 trial included non-diabetic men ( n=168 ) with a fasting plasma triglyceride concentration > or = 1.7 and or = 140 and or = 90 and or = 0.95 . METHODS A r and omised double-blind trial comparing metformin treatment ( 850 mg bid ) with placebo . RESULTS Metformin had no significant effect either on blood pressure or plasma triglyceride concentration . In comparison with the placebo group , fasting plasma insulin ( p total cholesterol ( p Apo B ( p concentrations decreased more in the metformin group in the BIGPRO 1 . 2 trial , confirming most of the previous results of the BIGPRO 1 trial . Tissue plasminogen activator antigen concentration decreased significantly ( p metformin group , but this was not significantly different from the placebo group ( p inhibitor 1 . CONCLUSIONS The consistency of the two BIGPRO trials supports the conclusion that metformin affects several cardiovascular risk factors favourably in non-diabetic subjects with a central fat distribution", "OBJECTIVE To study whether metformin reduces obesity , homeostasis model assessment for insulin resistance index ( HOMA-IR ) , and the metabolic syndrome ( MtS ) in obese European adolescents in addition to previous unsuccessful lifestyle intervention . DESIGN AND METHODS After 6 months of multiprofessional lifestyle intervention , 70 out of 86 adolescents without improvement in body mass index ( BMI ) and HOMA-IR were r and omized into either the placebo ( n=34 ) or the metformin group ( 2 × 500 mg/day , n=36 ) in addition to ongoing lifestyle intervention for another 6 months . RESULTS Age was 13.8 years , BMI was 33.1 kg/m(2 ) , 65 % were female , and 89 % were Caucasians . During lifestyle intervention alone , BMI and HOMA-IR deteriorated significantly . In the subsequent medication period , HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups ( HOMA-IR decreased 73 vs 54 % respectively in metformin versus placebo ; P=0.048 ) , but BMI remained unchanged . The insulin sensitivity index , however , only improved in the metformin group . High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication . MtS remained unchanged . CONCLUSIONS Obese European adolescents ' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention . Most differences did not reach statistical significance , probably due to improved compliance with lifestyle intervention as a placebo effect . In addition , the metformin dose may be too low", "Background The efficacy of pharmacological treatment in controlling childhood obesity is controversial . We aim ed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification ( diet and exercise ) . Methods This triple-masked r and omized clinical trial was conducted among 180 participants aged 10–16 years . They were assigned r and omly to 4 groups of equal number to receive metformin , fluoxetine , a combination of the two drugs , or placebo . The trial lasted for 12 weeks and participants were followed up for an additional 12-week period . Results Overall , 91.1 % ( n=164 ) of the enrolled participants completed the trial . After the 12-week trial , the body mass index decreased significantly in all groups receiving medications [ approximately −1.2 ( 0.2 ) kg/m2 , P group . Waist circumference decreased significantly in the groups receiving metformin [ −2.1 ( 0.4 ) cm , P=0.03 ) ] as well as in the group receiving a combination therapy of metformin and fluoxetine [ −2.5 ( 0.4 ) cm , P=0.01 ) ] . In the 24-week follow-up study , these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine . No serious drug side-effects were reported . Conclusions A limited period of such treatment may help weight control , and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs . Our findings should be confirmed in future studies with a longer follow-up period", "OBJECTIVE To evaluate the effects of metformin on glucagon-like peptide 1 ( GLP-1 ) and leptin levels . RESEARCH DESIGN AND METHODS A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects . On days 0 and 15 , leptin and GLP-1(7 - 36)amide/(7 - 37 ) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion . The effects of metformin on GLP-1(7 - 36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV ( DPP-IV ) were also studied . RESULTS Leptin levels were not affected by the oral glucose load , and they were not modified after metformin treatment . Metformin induced a significant ( P GLP-1(7 - 36)amide/(7 - 37 ) at 30 and 60 min after the oral glucose load ( 63.8 + /- 29.0 vs. 50.3 + /- 15.6 pmol/l and 75.8 + /- 35.4 vs. 46.9 + /- 20.0 pmol/l , respectively ) , without affecting baseline GLP-1 levels . No variations of GLP-1 levels were observed in the control group . In pooled human plasma , metformin ( 0.1 - 0.5 microg/ml ) significantly inhibited degradation of GLP-1(7 - 36)amide after a 30-min incubation at 37 degrees C ; similar results were obtained in a buffer solution containing DPP-IV . CONCLUSIONS Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects ; this effect could be due to an inhibition of GLP-1 degradation", "AIMS To evaluate the effect of metformin on glucose metabolism , insulin sensitivity and rate of conversion diabetes in people with impaired glucose tolerance ( IGT ) . METHODS Seventy subjects with IGT were r and omized under double-blind conditions to receive either placebo ( n = 37 ) or metformin ( n = 33 ) at a dosage of 250 mg three times daily for a duration of 12 months . Glycaemic control , plasma insulin and other biochemical indexes were assessed before and after 3 , 6 and 12 months . RESULT At 12 months the conversion rate to diabetes was 16.2 % in the placebo group compared to 3.0 % for the metformin group ( P = 0.011 ) . Of subjects treated with metformin for 12 months , 84.9 % became normoglycaemic compared to 51.4 % of those receiving the placebo . Significant improvements in fasting glucose , glucose tolerance and insulin sensitivity were found at 12 months and at intermediate clinic assessment s. CONCLUSIONS Metformin can improve glucose metabolism in IGT patients and may be a treatment option in their management of IGT subjects", "Abstract Objective : To determine if metformin improves markers of inflammation , thrombosis , and intrahepatic fat contents in children with uncomplicated obesity . Methods : Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein ( hsCRP ) and /or fibrinogen concentrations ( > 2 st and ard deviations ) were r and omized to structured diet/exercise or diet/exercise and metformin for 6 months . Blood sample s , dual energy X-ray absorptiometry data , and liver magnetic resonance images were obtained . Results : Forty-two of 66 recruited children ( 7–18 years ) completed 6 months . Weight loss was modest but more pronounced in the metformin group ( –4.9±1.0 kg ) than in the diet/exercise group ( –1.7±1.1 kg , p whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group . Baseline intrahepatic fat was high but decreased only in the diet/exercise ( not metformin ) pubertal group . Conclusions : Six months of metformin therapy improved weight loss and reduced abdominal adiposity , but did not enhance the beneficial effect of diet and exercise on markers related to inflammation , thrombosis , or hepatic fat in obese children with normal glucose tolerance", "The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance , and the effect of metformin on these parameters evaluated . Fifty obese , multiethnic , insulin-resistant adolescents ( mean age 15.1 yr , mean body mass index 39.8 kg/m2 ) were r and omized to receive lifestyle recommendations plus either twice per day doses of 850 mg of metformin or placebo . Fasting and post-glucose challenge biochemistries and liver ultrasounds were compared at baseline and 6 months . The prevalence of fatty liver was 74 % , elevated alanine aminotransferase ( ALT ) 14 % , aspartate aminotransferase ( AST ) 14 % , and gamma-glutamyl transferase ( GGT ) 17 % . Fatty liver was mild in 23 % , moderate in 31 % , and severe in 46 % . Fatty liver was more common in male and Hispanic subjects and elevated ALT more common in Hispanic subjects . Subjects with fatty liver appeared more insulin resistant ( higher fasting insulin and triglycerides , lower high-density lipoprotein cholesterol ) and had higher ALT and AST . At 6 months , mean ALT , GGT , and fasting insulin improved significantly in all subjects . Fatty liver prevalence ( p severity ( p and fasting insulin ( p Non-alcoholic fatty liver disease ( NAFLD ) occurs with a high prevalence and severity in obese , insulin-resistant adolescents . While metformin plus lifestyle intervention appears promising , defining NAFLD therapies capable of preventing fibrosis and cirrhosis requires further study", "Abstract Objective : To compare serum concentrations of inflammatory cytokines , interleukin 6 ( IL-6 ) , high-sensitivity C-reactive protein ( hs-CRP ) , adiponectin , and tumor necrosis factor α ( TNFα ) , before and after 3 months treatment with metformin in obese adolescents with insulin resistance ( IR ) . Design and subjects : This was a r and omized , double-blinded , clinical trial of two groups of obese adolescents with IR , aged 9–18 years : a placebo group ( n=14 ) and a metformin group ( n=12 ) who received 500 mg metformin every 12 h for 3 months . Anthropometric and biochemical ( metabolic and inflammatory cytokines ) assessment s were compared at the beginning and end of treatment . Results : After 3 months of treatment , body mass index ( kg/m2 ) was reduced in both groups : placebo group ( 32.82±6.37–32.10±6.52 ; p=0.011 ) and metformin group ( 33.44±5.82–32.71±5.77 ; p=0.015 ) . Serum fasting insulin concentrations ( pmol/L ) increased in the placebo group ( 189.45±112.64–266.06±167.79 ; p=0.01 ) and showed a slight decrease in the metformin group ( 256.82±113.89–229.25±86.53 ; p=0.64 ) . Adiponectin concentrations ( μg/mL ) decreased in the placebo group ( 13.17±7.31–5.65±6.69 ; p=0.02 ) , while these remained stable in the metformin group ( 8.57±3.98–7.86±6.23 ; p=0.64 ) . In the metformin group , significant reductions were found in the variances of serum TNFα concentrations ( p=0.006 ; Levene test ) . Conclusion : These results suggest that treating obese adolescents with IR using metformin for 3 months is an option for patients without response to traditional lifestyle change because metformin improves inflammatory activity , which is an etiological factor in cardiovascular disease development", "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", "Abstract Aim This study was undertaken to determine whether metformin would ameliorate insulin resistance , reduce weight and waist circumference and improve lipids in obese , but not morbidly obese , euglycemic women . Methods Obese women ( body mass index ( BMI ) ≥ 30 and 88 cm ) , aged 35–65 were r and omized ( 1:1 ) to metformin 850 mg or identical placebo , twice daily for 26 weeks . The primary outcome was the change in insulin resistance determined by the homeostasis model of assessment ( HOMA-IR ) . Secondary outcomes included fasting insulin , glucose , weight , waist circumference and BMI . Results Of the 125 women screened , 117 enrolled and 100 women , mean age 53 years , were included in the primary intention-to-treat analysis . Metformin result ed in statistically significant between-group difference in the change in HOMA-IR ( change in median − 0.04 vs. placebo + 0.1 , p = 0.018 ) and BMI ( mean change − 1.00 kg/m2 ; 95 % confidence interval ( CI ) 1.37 to − 0.62 vs. placebo mean change 0.00 ; 95 % CI − 0.29 to 0.28 , p in HbA1c ( p = 0.008 ) and fasting insulin ( p = 0.03 ) and a borderline decrease in high density lipoprotein cholesterol ( p = 0.07 ) were also observed for metformin , compared with placebo . No effects were seen for waist circumference , fasting glucose or other lipids . Conclusion Treatment of euglycemic , obese , middle-aged women with metformin 1700 mg per day reduced insulin resistance and weight compared with placebo . Further studies are needed to determine whether the use of metformin will prevent the progression of insulin resistance to type 2 diabetes mellitus in obese women", "The objective was to determine the effect of metformin on the concentrations of resistin and other markers of insulin resistance or inflammation ( C-reactive protein , cytokines , body weight , HbA1c , among others ) in minors with glucose intolerance . Patients aged 4 to 17 years with glucose intolerance were studied . They were r and omized to receive 850 mg of either metformin or placebo twice daily for 12 weeks , during which all followed an iso-caloric diet and an exercise program . High sensitivity C-reactive protein , TNF-alpha , IL-6 , IL1-beta , resistin , leptin , adiponectin , glucose , insulin , HbA1c , lipid profile and transaminases were measured at the beginning and at the end of the period . Fifty-two patients were included , 11.9±2.6 years old ; 28 ( 12 males/16 females ) received metformin and 24 placebo ( 11 males/13 females ) . Baseline characteristics were similar between groups ( except for body mass index , which in the metformin group was slightly higher ) . Percentage weight loss was greater in the metformin group ( -5.86 % vs 2.75 % , P in resistin concentrations , even after adjusting for confounding variables ( F=7.714 ; P Also , metformin was associated with a significant decrease in HOMA-IR index ( P=.032 ) and HbA1c levels ( P=.001 ) , but no change was observed in the concentration of other markers of inflammation . Metformin result ed in significant reductions of plasma resistin levels in minors with glucose intolerance . This change is independent of its effects on body weight . In contrast , metformin did not alter the concentration of inflammatory markers ", "PURPOSE Obesity in adolescence increases the risk for early adult cardiovascular disease . We recently showed that 6 months of diet , exercise , and metformin result ed in reductions in adiposity and that diet/exercise alone reduced proinflammatory factors and intrahepatic fat in pubertal children with uncomplicated obesity . The purpose of the present study was to determine whether changes in cardiorespiratory fitness ( CRF ) after 6 months of structured diet and exercise ( DE ) or DE plus metformin are related to the previously observed changes in adiposity , markers of inflammation , and intrahepatic fat . METHODS Sixteen obese pubertal adolescents between the ages of 10 and 17 were r and omized into a structured lifestyle program consisting of DE or DE plus metformin . Subjects performed aerobic and resistance exercise 3 d·wk⁻¹ , 30 min per session . Cycle ergometer maximal oxygen consumption ( V˙O2max ) , body composition , blood markers ( glucose , insulin , homeostatic model assessment -insulin resistance , interleukin-6 , hsCRP ) , and intrahepatic fat were measured at baseline and 6 months . RESULTS In the cohort , as whole-body weight decreased by 4.0 % ( P = 0.009 ) , body mass index decreased by 4.9 % ( P = 0.003 ) , percent body fat decreased by 8.8 % ( P addition of metformin provided no further effect on body composition , CRF , or inflammatory factors . More favorable changes in adiposity , adiponectin , and a trend toward blood glucose and interleukin-6 concentrations ( P = 0.07 ) were observed in subjects who increased V˙O2max at 6 months ( n = 10 ) compared with no change in these variables in those who did not improve V˙O2max . CONCLUSIONS Metformin did not provide benefits above lifestyle modification for improving CRF in obese adolescents . Improvements in V˙O2max seem to be associated with more favorable metabolic outcomes", "CONTEXT Childhood obesity is increasingly associated with type 2 diabetes ( T2D ) . Metformin reduces the risk for T2D in adult obese nondiabetic patients , but the evidence in obese children and young people is inconclusive . OBJECTIVE The objective of the study was to assess the effect of metformin on body mass index sd score ( BMI -SDS ) , metabolic risk factors , and adipokines . DESIGN This was a prospect i ve , r and omized , double-blind , placebo-controlled trial . SETTING The study was conducted at six pediatric endocrine centers in the United Kingdom . PARTICIPANTS One hundred fifty-one obese children and young people with hyperinsulinemia and /or impaired fasting glucose or impaired glucose tolerance ( metformin : 74 , placebo : 77 ) . The study was comprised of 67.5 % females , 65.6 % postpubertal individuals , and 23.8 % British Asian or Afro-Caribbean participants . The age range was 8 - 18 yr , the mean age was 13.7 ( SD 2.3 ) yr , and the mean BMI -SDS was + 3.4 ( SD 0.5 ) . INTERVENTIONS The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months . MAIN OUTCOME MEASURE The main outcome measure was a reduction in BMI -SDS at 6 months . Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests , alanine aminotransferase ( ALT ) , and adiponectin to leptin ratio ( ALR ) at 3 and 6 months . RESULTS Metformin was associated with a significant reduction in BMI -SDS compared with placebo at 6 months [ mean difference -0.1 SD ( 95 % confidence interval -0.18 to -0.02 ) , P = 0.02 ] . Significant improvements at 3 months were found in the metformin group : fasting glucose , -0.16 mmol/liter ( -0.31 to -0.00 ) , P = 0.047 ; ALT , 19 % ( 5 - 36 % ) , P = 0.008 ; and ALR , 32 % ( 4 - 67 % ) , P = 0.02 . CONCLUSIONS Metformin therapy has a beneficial treatment effect over placebo for BMI -SDS , fasting glucose , ALT , and ALR ratio at 3 months , with changes in BMI -SDS sustained at 6 months", "Introduction The aim of this study was to investigate the efficacy and safety of linagliptin + low-dose ( LD ) metformin once daily versus high-dose ( HD ) metformin twice daily in treatment-naïve patients with type 2 diabetes . Methods Patients ( n = 689 ) were r and omized ( 1:1 ) to double-blind treatment with linagliptin 5 mg + LD metformin ( 1000 mg ) or HD metformin ( 2000 mg ) for 14 weeks . Metformin was initiated at 500 mg/day and up-titrated within 2 weeks ; the dose then remained unchanged . The primary endpoint was change in glycated hemoglobin ( HbA1c ) from baseline to Week 14 in patients who tolerated a daily metformin dose of ≥1000 mg after 2 weeks . Results At Week 14 , HbA1c changed from a mean baseline of 8.0 % ( 64 mmol/mol ) by −0.99 % ( −11 mmol/mol ) for linagliptin + LD metformin , and −0.98 % ( −11 mmol/mol ) for HD metformin [ treatment difference −0.01 % ( 95 % confidence interval −0.13 , 0.12 ) ( 0 mmol/mol ) , P = 0.8924 ] . The proportion of patients who achieved HbA1c of moderate or severe gastrointestinal ( GI ) events ( including abdominal pain , nausea , vomiting , diarrhea , and decreased appetite ) was the same in both groups ( 51.3 % for both ) . Although the occurrence of moderate or severe GI events was similar , the linagliptin + LD metformin group had fewer mild GI events ( 18.5 % versus 24.3 % ) . The incidence of hypoglycemia was low in both groups . Conclusion Linagliptin + LD metformin combination showed similar efficacy and safety to HD metformin . This combination may be an alternative treatment option in patients who may have difficulty tolerating metformin doses > 1000 mg/day . Funding Boehringer Ingelheim", "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 .", "BACKGROUND AND AIM Young women are at high risk of weight gain but few weight management interventions have been investigated in this group . This study aim ed to determine the effect of metformin on body weight , body composition , metabolic risk factors and reproductive hormone levels in overweight or obese young women compared to placebo and comprehensive lifestyle intervention . METHODS AND RESULTS 203 overweight or obese young women ( BMI 33.2+/-0.3 kg/m² , age 28+/-0.3 years ) were r and omised to 1500 mg/day metformin ( M ) plus general lifestyle advice , placebo ( P ) plus general lifestyle advice or comprehensive lifestyle intervention including structured diet , exercise and behavioural therapy ( L ) for 12-weeks . At 12-weeks , linear mixed models found that L group had greater weight loss ( -4.2+/-0.4 kg ) compared to M ( -1.0+/-0.4 kg ) and P groups ( -0.2+/-0.3 kg ) ( P between M and P groups were not significantly different . Attrition rate was 48 % for L , 34 % for M and 29 % for P ( P = 0.08 ) . Intention-to-treat analysis showed that 10 % ( 8/79 ) of the subjects in P group had gained weight ( > 3 % ) , compared to 3 % ( 2/65 ) from M group and none ( 0/59 ) from L group ( P decrease in waist circumference ( -5.2+/-0.7 cm ) and fat mass ( -5.4+/-0.7 kg ) compared to the other groups ( P seen in plasma lipids , SHBG , testosterone , blood pressure , serum folate , serum ferritin and serum vitamin B12 . CONCLUSION Lifestyle intervention was more effective in reducing body weight and improving body composition compared to metformin among healthy overweight or obese young women", "OBJECTIVE To evaluate whether metformin , when added to a program of personal goal setting , improves weight loss and clinical status in obese adolescents . STUDY DESIGN In a r and omized double-blind placebo controlled trial , 85 adolescents with insulin resistance were r and omized to receive metformin ( 70 % ) or placebo ( 30 % ) , along with monthly goal setting for diet and exercise modification . Anthropometric measures , fasting blood analysis , and glucose tolerance tests were performed at baseline and 6 months . RESULTS Mean age was 15.7 years . Mean body mass index ( BMI ) was 39.7 kg/m(2 ) . 71 % were female , 58 % were Hispanic , and 34 % were African-American . 76 % of participants completed the study . Goal setting alone did not result in significant weight loss . In addition , there were no group differences between metformin and placebo in weight loss or measures of glucose metabolism . However , among females taking metformin , there was a significant decrease in BMI not seen in the placebo group . Furthermore , metformin adherence , when accompanied by lifestyle change , was a predictor of BMI decrease of 5 % or more . 60 % of 10 subjects who adhered to metformin and decreased portion size decreased BMI by > 5 % . CONCLUSIONS In this group of predominately minority adolescents , monthly goal setting alone did not lead to weight loss . Although the addition of metformin had no effect on weight loss overall , the agent did significantly increase weight loss among females and weight loss was predicted by degree of metformin adherence . However , weight loss was only found in those participants also reporting lifestyle change , particularly a decrease in portion sizes . These results suggest that metformin may be a useful agent to promote short-term weight loss among girls making modest lifestyle changes ", "Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals . It has been demonstrated that metformin , an antihyperglycemic agent , decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus ( NIDDM ) adults . To evaluate the antiobesity effect of metformin , we conducted a r and omized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents ( body mass index [ BMI ] > 30 kg/m(2 ) ) . All subjects were placed on a low-calorie ( 1,500 kcal for women and 1,800 kcal for men ) meal plan . After an initial 1-week lead-in period , 12 subjects ( mean + /- SE for age and BMI , 15.6 + /- 0.4 and 41.2 + /- 1.8 , respectively ) received metformin ( 850 mg twice daily ) for 8 weeks , and 12 subjects ( mean + /- SE for age and BMI , 15.7 + /- 0.5 and 40.8 + /- 1.4 , respectively ) received placebo . Compared to the placebo group , the metformin group had greater weight loss ( 6.5 % + /- 0.8 % v 3.8 + /- 0.4 % , P body fat ( P fat-free mass to body fat ratio ( P attenuation of area under the curve ( AUC ) insulin response to an oral glucose tolerance test ( P insulin sensitivity , as determined by the fasting plasma glucose : insulin , 2-hour glucose : insulin , and AUC glucose : AUC insulin ratios , in the metformin group compared to controls ( P plasma leptin ( P cholesterol , triglycerides , and free fatty acid ( FFA ) levels ( P metformin-treated subjects . Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone", "BACKGROUND Metformin has been proffered as a therapy for adolescent obesity , although long-term controlled studies have not been reported . OBJECTIVE To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release ( XR ) therapy will reduce body mass index ( BMI ) in obese adolescents , as compared with placebo . DESIGN Multicenter , r and omized , double-blind , placebo-controlled clinical trial . SETTING The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007 . PARTICIPANTS Obese ( BMI > or = 95th percentile ) adolescents ( aged 13 - 18 years ) were r and omly assigned to the intervention ( n = 39 ) or placebo groups . Intervention Following a 1-month run-in period , subjects following a lifestyle intervention program were r and omized 1:1 to 48 weeks ' treatment with metformin hydrochloride XR , 2000 mg once daily , or an identical placebo . Subjects were monitored for an additional 48 weeks . Main Outcome Measure Change in BMI , adjusted for site , sex , race , ethnicity , and age and metformin vs placebo . RESULTS After 48 weeks , mean ( SE ) adjusted BMI increased 0.2 ( 0.5 ) in the placebo group and decreased 0.9 ( 0.5 ) in the metformin XR group ( P = .03 ) . This difference persisted for 12 to 24 weeks after cessation of treatment . No significant effects of metformin on body composition , abdominal fat , or insulin indices were observed . CONCLUSION Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00209482 and NCT00120146", "BACKGROUND It has been hypothesized that metformin inhibits food intake , but in humans such effect needs to be demonstrated . Our study aims at investigating the effect of metformin administration on food intake in obese , non-diabetic , normotensive patients . METHODS Thirty patients underwent a double-blind , r and omized study . Placebo ( P ; n = 15 ) and metformin ( M ; n = 15 ) were both given for 15 days , and food intake ( FI ) was recorded at baseline and in the last 4 days of each treatment period . RESULTS M administration allowed a stronger decline in body weight ( BW ) ( -2.8 + /- 1.6 vs. -0.3 + /- 0.4 kg P body fat ( BF ) ( -1.4 + /- 1.2 vs. -0.3 + /- 1.1 kg P plasma leptin concentration ( -5.2 + /- 8.9 vs. -1.8 + /- 10.4 ng mL-1 P FI ( -642 + /- 491 vs.-70 + /- 1165 kJ per 24 h P changes in FI significantly correlated with those in BW ( r = 0.63 , P BF ( r = 0.74 , P FI and in fasting plasma leptin concentration ( r = 0.58 , P metformin administration is useful to inhibit FI and to lower BW and BF in obese non-diabetic patients", "Metformin improves insulin sensitivity , which is correlated to phospholipid fatty acid composition in obese type 2 diabetics . We aim ed at investigating the relationship between Metformin and fatty acids in obese insulin resistant non-diabetic individuals . A double-blind , placebo-controlled 20-week trial was performed in 21 BMI and age-matched insulin resistant non-diabetic individuals receiving either Metformin or placebo . Insulin sensitivity together with metabolic parameters and fatty acids in serum phospholipids were measured at baseline and at 20 weeks . A significant decrease in body weight , BMI , percentage body fat , the sum of saturated fatty acids in serum phospholipids and increase in insulin sensitivity index were observed following the 20-week treatment . These changes did not differ significantly between the groups . Energy restriction rather than Metformin treatment appears to be responsible for the observed changes . The associations previously found in diabetics between insulin sensitivity and phospholipid fatty acids may not be mediated by Metformin", "OBJECTIVES To measure the effect of metformin on the body composition , insulin resistance and sensitivity in subjects with risk factors for type 2 diabetes mellitus ( type 2 DM ) . DESIGN Placebo-controlled clinical trial . MATERIAL AND METHODS Twenty-three subjects with risk factors for type 2 DM were r and omly assigned to receive 850 mg of metformin or a placebo twice a day for 2 months . Before and after the treatment , the body mass index and waist/hip ratio were calculated , the body composition was measured through bioelectric impedance and the fasting levels of blood glucose , insulin , triglycerides and cholesterol were measured . The level of insulin resistance was calculated by the homeostatic model and the level of sensitivity by the quantitative insulin sensitivity check index method . The Wilcoxon rank test was used . RESULTS Twenty-one subjects completed the study , 12 of the metformin group and nine of the placebo group . In the metformin group , there was a decrease in fat weight from 25.9 + /- 9.4 to 20.8 + /- 9.2 kg , p lean weight from 57.05 + /- 13.6 to 61.9 + /- 16.5 kg , p basal metabolism from 1735 + /- 413 to 1878 + /- 505 calories/day , p body water , p insulin resistance . In the placebo group , the blood glucose increased from 84.7 + /- 13 to 96.7 + /- 16 mg/dl , p lipids . CONCLUSIONS The administration of metformin for 2 months improves the parameters of body composition and insulin dynamics in subjects with risk factors for type 2 DM", "CONTEXT Metformin therapy for adults and children with type 2 diabetes is well established . However , its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined . OBJECTIVE We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity . DESIGN AND SETTING Patients referred to a pediatric endocrine clinic were enrolled in a r and omized , double-blind , crossover trial . PATIENTS Twenty-eight patients ( 13 males ) aged 9 - 18 yr participated in the study . INTERVENTION Patients received metformin ( 1 g twice daily ) and placebo for 6 months , each with a 2-wk washout period . MAIN OUTCOME MEASURES Body composition ( anthropometry , dual-energy x-ray absorptiometry , and abdominal magnetic resonance imaging ) , and insulin sensitivity ( Si ; minimal model , fasting insulin and glucose ) were measured at baseline and 6 and 12 months . RESULTS Mean age of subjects at baseline was 12.5 + /- 2.2 yr , median body mass index z-score 2.54 ( range , 1.93 - 2.85 ) . Metformin had a greater treatment effect over placebo for weight ( -4.35 kg , P = 0.02 ) , body mass index ( -1.26 kg/m(2 ) , P = 0.002 ) , waist circumference ( -2.8 cm , P = 0.003 ) , sc abdominal adipose tissue ( -52.5 cm(2 ) , P = 0.002 ) , and fasting insulin ( -2.2 mU/liter , P = 0.011 ) . Si improved in 45 % of subjects while on metformin and 27 % of subjects while on placebo ( P = 0.21 ) . CONCLUSIONS Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin . Although improvement in Si was noted in many individuals , Si was a less useful parameter for analysis of group data , possibly because of effects of variable compliance and changing Si during puberty" ]

[ "OBJECTIVES To investigate the predictive validity and reliability of the STRATIFY falls risk assessment tool as applied to patients recovering from acute stroke . DESIGN Prospect i ve cohort study . SETTING Six stroke rehabilitation units in the North of Engl and . SUBJECTS All patients with a diagnosis of acute stroke admitted to the participating stroke units during a 6-month study period . ASSESSMENT on admission , falls risk ( STRATIFY ) , disability ( Barthel index ) , mobility ( Rivermead mobility index ) , cognitive impairment ( abbreviated mental test score ) and visual neglect ( Albert 's test ) were assessed . Then , STRATIFY was completed weekly and within 48 h of anticipated discharge . Consenting patients were contacted at 3 months after discharge to determine falls . OUTCOME MEASURES Occurrence of a fall within 28 days of the baseline STRATIFY ( in-patient study ) , falls in the first 3 months after discharge ( post-discharge study ) and falls during stroke unit stay ( reliability study ) . RESULTS From 387 patients admitted to the participating units during the study period , 225 contributed to the 28 day in-patient study , and 234 were followed up at 3 months after discharge . STRATIFY performed poorly in predicting falls in the first 28 days ( sensitivity 11.3 % and specificity 89.5 % ) and after discharge ( sensitivity 16.3 % and specificity 86.4 % ) . Agreement was ' fair ' between baseline and discharge scores ( kappa = 0.263 ) and ' good ' between the pre-hospital discharge score and that obtained in the week preceding discharge ( kappa = 0.639 ) . CONCLUSION STRATIFY performed poorly as a predictor of falls in a heterogeneous population of stroke patients . There is a need for a disease-specific rather than a generic falls risk assessment tool", "Abstract Objective To assess the effectiveness of a targeted , multiple intervention falls prevention programme in reducing falls and injuries related to falls in a subacute hospital . Design R and omised controlled trial of a targeted multiple intervention programme implemented in addition to usual care compared with usual care alone . Setting Three subacute wards in a metropolitan hospital specialising in rehabilitation and care of elderly patients . Participants 626 men and women aged 38 to 99 years ( average 80 years ) were recruited from consecutive admissions to subacute hospital wards . Intervention Falls risk alert card with information brochure , exercise programme , education programme , and hip protectors . Main outcome measures Incidence rate of falls , injuries related to falls , and proportion of participants who experienced one or more falls during their stay in hospital . Results Participants in the intervention group ( n = 310 ) experienced 30 % fewer falls than participants in the control group ( n = 316 ) . This difference was significant ( Peto log rank test P = 0.045 ) and was most obvious after 45 days of observation . In the intervention group there was a trend for a reduction in the proportion of participants who experienced falls ( relative risk 0.78 , 95 % confidence interval 0.56 to 1.06 ) and 28 % fewer falls result ed in injury ( log rank test P = 0.20 ) . Conclusions A targeted multiple intervention falls prevention programme reduces the incidence of falls in the subacute hospital setting", "The performance of a predictive model is overestimated when simply determined on the sample of subjects that was used to construct the model . Several internal validation methods are available that aim to provide a more accurate estimate of model performance in new subjects . We evaluated several variants of split- sample , cross-validation and bootstrapping methods with a logistic regression model that included eight predictors for 30-day mortality after an acute myocardial infa rct ion . R and om sample s with a size between n = 572 and n = 9165 were drawn from a large data set ( GUSTO-I ; n = 40,830 ; 2851 deaths ) to reflect modeling in data sets with between 5 and 80 events per variable . Independent performance was determined on the remaining subjects . Performance measures included discriminative ability , calibration and overall accuracy . We found that split- sample analyses gave overly pessimistic estimates of performance , with large variability . Cross-validation on 10 % of the sample had low bias and low variability , but was not suitable for all performance measures . Internal validity could best be estimated with bootstrapping , which provided stable estimates with low bias . We conclude that split- sample validation is inefficient , and recommend bootstrapping for estimation of internal validity of a predictive logistic regression model", "Objective : To further assess the validity and inter-rater reliability of the Elderly Mobility Scale ( EMS ) . Also whether the scale reflects elderly people 's perceptions regarding their mobility , and whether it can predict discharge destination , or likelihood of falling . Design : Question naire-based study completed on admission and weekly after this on all patients referred to physiotherapy for mobility problems over the course of one month . Setting : Care of the elderly wards in the Bristol General Hospital . Subjects : Sixty-six patients ( ages 66 - 69 years , 66 % female ) were included in the validity study . Nineteen patients ( ages 71 - 95 years , 47 % female ) were included in the inter-rater reliability study . Interventions : EMS , Barthel and patients ' perceptions of mobility were tested with routine physiotherapy treatment carried out as necessary . Main outcome measures : Concurrent validity was assessed by correlating EMS scores with Barthel scores using Spearman 's test . Inter-rater reliability was also tested using a Spearman 's correlation . EMS scores of patients were also evaluated in conjunction with whether or not they fell and their destination on discharge . Results : A significant correlation between EMS and Barthel scores indicated concurrent validity . Inter-rater reliability was demonstrated on 19 patients with a significant correlation between scores . No predictive validity could be ascribed to EMS in terms of discharge destination or likelihood of falling . Results do indicate a possible predictive validity of the functional reach component of the EMS regarding the risk of future falls . Conclusions : The EMS was found to be a valid scale with good inter-rater reliability that could be readily applied during daily clinical work . However , it was found to have no predictive validity in terms of falling or discharge destination", "This purpose of this study was to determine whether an identification bracelet is effective in preventing falls among high-risk patients who are undergoing in-patient physical rehabilitation . A stratified , r and omized , balanced controlled clinical trial was conducted ; participants were blinded as to the outcome and the study hypothesis . All patients having one or more risk factors that predisposed them to falls were r and omized to receive either a blue identification bracelet or no bracelet . The identification bracelet was intended to increase patients ' vigilance about falling . Two risk strata were specified . The high risk stratum consisted of patients with stroke or ataxia , urinary incontinence , or a history of falls . The low risk stratum comprised patients older than 80 years and those on one or more medications that had been identified as contributing to an individual 's risk of falling . This report presents the effect of the identification bracelet only among persons in the high-risk stratum . Over 1 year , 65 high-risk subjects were r and omized to receive the blue identification bracelet and 69 high-risk subjects were controls . In the intervention group , 27 persons ( 41 % ) fell at least once , whereas in the control group 21 persons ( 30 % ) fell at least once yielding a hazard ratio of 1.3 ( 95 % confidence interval : 0.8 to 2.4 ) . These results suggest that the identification system was of no benefit in preventing falls among high-risk persons", "Background The British STRATIFY tool was previously developed to predict falls in hospital . Although the tool has several strengths , certain limitations exist which may not allow generalizability to a Canadian setting . Thus , we tested the STRATIFY tool with some modification and re-weighting of items in Canadian hospitals . Methods This was a prospect i ve validation cohort study in four acute care medical units of two teaching hospitals in Hamilton , Ontario . In total , 620 patients over the age of 65 years admitted during a 6-month period . Five patient characteristics found to be risk factors for falls in the British STRATIFY study were tested for predictive validity . The characteristics included history of falls , mental impairment , visual impairment , toileting , and dependency in transfers and mobility . Multivariate logistic regression was used to obtain optimal weights for the construction of a risk score . A receiver-operating characteristic curve was generated to show sensitivities and specificities for predicting falls based on different threshold scores for considering patients at high risk . Results Inter-rater reliability for the weighted risk score indicated very good agreement ( inter-class correlation coefficient = 0.78 ) . History of falls , mental impairment , toileting difficulties , and dependency in transfer / mobility significantly predicted fallers . In the multivariate model , mental status was a significant predictor ( P history of falls and transfer / mobility difficulties approached significance ( P = 0.089 and P = 0.077 respectively ) . The logistic regression model led to weights for a risk score on a 30-point scale . A risk score of 9 or more gave a sensitivity of 91 % and specificity of 60 % for predicting who would fall . Conclusion Good predictive validity for identifying fallers was achieved in a Canadian setting using a simple-to-obtain risk score that can easily be incorporated into practice", "Abstract Objectives : To identify clinical characteristics of elderly in patients that predict their chance of falling ( phase 1 ) and to use these characteristics to derive a risk assessment tool and to evaluate its power in predicting falls ( phases 2 and 3 ) . Design : Phase 1 : a prospect i ve case-control study . Phases 2 and 3 : prospect i ve evaluations of the derived risk assessment tool in predicting falls in two cohorts . Setting : Elderly care units of St Thomas 's Hospital ( phase 1 and 2 ) and Kent and Canterbury Hospital ( phase 3 ) . Subjects : Elderly hospital in patients ( aged 65 years ) : 116 cases and 116 controls in phase 1 , 217 patients in phase 2 , and 331 in phase 3 . Main outcome measures : 21 separate clinical characteristics were assessed in phase 1 , including the abbreviated mental test score , modified Barthel index , a transfer and mobility score obtained by combining the transfer and mobility sections of the Barthel index , and several nursing judgments . Results : In phase 1 five factors were independently associated with a higher risk of falls : fall as a presenting complaint ( odds ratio 4.64 ( 95 % confidence interval 2.59 to 8.33 ) ; a transfer and mobility score of 3 or 4 ( 2.10 ( 1.22 to 3.61 ) ) ; and primary nurses ' judgment that a patient was agitated ( 20.9 ( 9.62 to 45.62 ) ) , needed frequent toileting ( 2.48 ( 1.08 to 5.70 ) ) , and was visually impaired ( 3.56 ( 1.26 to 10.05 ) ) . A risk assessment score ( range 0 - 5 ) was derived by scoring one point for each of these five factors . In phases 2 and 3 a risk assessment score > 2 was used to define high risk : the sensitivity and specificity of the score to predict falls during the following week was 93 % and 88 % respectively in phase 2 and 92 % and 68 % respectively in phase 3 . Conclusion : This simple risk assessment tool predicted with clinical ly useful sensitivity and specificity a high percentage of falls among elderly hospital in patients", "In order to compare the characteristics , preventive interventions and outcomes of single and multiple fallers , a retrospective cross-sectional study was conducted in a 680-bed acute-care hospital in Western Australia . Fifty patients falling more than once ( multiple fallers ) were r and omly selected from all patients reported to have fallen between 1 July 1989 and 31 December 1989 , and age-sex matched with 50 patients falling once in the trial period ( single fallers ) . In total , 382 in- patients were reported to have sustained 578 falls in the 6-month trial period . Fifty-two per cent of these falls involved multiple fallers . An analysis of the 100 single and multiple fallers showed that single fallers were more likely to have fallen from their bed ; be discharged home from hospital ; and be clinical ly deteriorating at the time of the fall . Multiple fallers were more likely to be transferred to a long-term nursing facility after discharge from hospital ; suffer blindness/poor vision ; be se date d post fall ; be ordered to be restrained following a fall ; and be hospitalized for longer periods . There was also a tendency for multiple fallers to repeat the type and location of the fall on successive falls . Stepwise logistic regression showed that falling from the bed on the first fall predicted remaining a single faller . Being ordered to be restrained following the first fall and hospitalized for longer periods predicted the patient would fall repeatedly . Further analytical research incorporating an exp and ed number of independent variables is needed to allow confident assertions of causality . To test the effectiveness of preventive measures , a prospect i ve longitudinal study is required", "The consequences of falls among hospital patients are a great problem , for the patient , the family and society , and cost billions of dollars . In Sweden , almost one-third of all hip fractures occur in the hospital population . Despite this , very few prevention strategies have been developed and tested . In this study , a risk assessment and recording programme in relation to the risk of falling among patients in a geriatric department at a Swedish hospital was implemented . The records of all patients admitted to a geriatric unit during one year , and a stratified r and om sample of patient records , constituting the control group from the year before , were review ed . No recording of assessment s regarding the patients ' risk of falling , and no preventive nursing interventions , were found in the records of the control group . The study group , however , increased the recording of risk assessment to 96 % . Only implemented nursing interventions were found in the patients ' records , despite the fact that Swedish law makes it obligatory for the registered nurse to record both the planning and implementation of nursing care . In the study group there were explicit descriptions of problems of concern for nursing regarding the patients ' risk of falling in less than one-third of the records , the nursing care plans were rare , and the evaluations were not satisfactory . Nursing interventions consisted mostly of information or education , promotion of patient participation , and structuring of the environment . There was no agreement on any st and ard-care plan . Recording of falls was found more often in the study group than in the control group ( probably due to more careful recording ) , but the proportion of injuries in relation to falls was higher in the control group . The results of this study may be used as a baseline for developing a nursing strategy and documentation relating to falls", "BACKGROUND falls and related injuries are known to be a significant problem for older people . There is evidence that identifying and addressing individual risk factors can reduce the incidence of falls in the community but no evidence of the effectiveness of targeted risk factor reduction methods applied to hospital in- patients . OBJECTIVE to test the efficacy of a targeted risk factor reduction core care plan in reducing risk of falling while in hospital . DESIGN a group ( ward ) r and omised trial . SETTING elderly care wards and associated community units of a district general hospital in the North of Engl and . SUBJECTS all elderly patients who received care in eight wards and community units during a 12-month study period . METHODS matched pairs of wards were r and omly allocated to intervention or control groups . In the intervention wards , staff used a pre-printed care plan for patients identified as at risk of falling and introduced appropriate remedial measures . Numbers of falls in each group were then compared . RESULTS after introduction of the care plan there was a significant reduction in the relative risk of recorded falls on intervention wards ( relative risk 0.79 , 95 % CI 0.65 - 0.95 ) but not on control wards ( RR 1.12 , 95 % CI 0.96 - 1.31 ) . The difference in change between the intervention wards and control wards was highly significant ( RR 0.71 , 95 % CI 0.55 - 0.90 , P = 0.006 ) . There was no significant reduction in the incidence of falls-related injuries . CONCLUSION the use of a core care plan targeting risk factor reduction in older hospital in- patients was associated with a reduction in the relative risk of recorded falls", "The present study examined the clinical efficacy of a bed alarm system in reducing falls from bed on a geriatric evaluation and treatment unit . A nine-month case-controlled study was design ed , in which 70 patients ( 60 women , 10 men ; mean age 84 years , range 67 - 97 years ) at increased risk for bed falls were r and omly assigned to either an experimental or a control group . Subjects in the experimental group ( n = 35 ) received a bed alarm system and those in the control group ( n = 35 ) did not . Outcome measures included bed falls , performance of the bed alarm system , and staff attitudes toward the use of the system . Although results failed to demonstrate a statistical difference in bed falls between the experimental ( n = 1 ) and control ( n = 4 ) groups ( p = 1.00 ) , there was a clinical trend toward reduced falls in the experimental group . The system functioned properly , activating an alarm in all instances when patients were transferring from bed , and with the exception of one case , nurses could respond in a timely fashion to assist patients and prevent bed falls . The system did not produce any adverse effects in patients , nor did the device interfere with the rendering of medical care . The system was well accepted by patients , families , and nurses . These data suggest that bed alarm systems are beneficial in guarding against bed falls and are an acceptable method of preventing falls", "BACKGROUND AND OBJECTIVE To describe the diagnostic accuracy and practical application of the Peter James Centre Falls Risk Assessment Tool ( PJC-FRAT ) , a multidisciplinary falls risk screening and intervention deployment instrument . METHODS In phase 1 , the accuracy of the PJC-FRAT was prospect ively compared to a gold st and ard ( the STRATIFY ) on a cohort of subacute hospital patients ( n = 122 ) . In phase 2 , the PJC-FRAT was temporally reassessed using a subsequent cohort ( n = 316 ) , with results compared to those of phase 1 . Primary outcomes were falls ( events ) , fallers ( patients who fell ) , and hospital completion rates of the PJC-FRAT . RESULTS In phase 1 , PJC-FRAT accuracy of identifying fallers showed sensitivity of 73 % ( bootstrap 95 % confidence interval CI = 55 , 90 ) and specificity of 75 % ( 95 % CI = 66 , 83 ) , compared with the STRATIFY ( cutoff > or = 2/5 ) sensitivity of 77 % ( 95 % CI = 59 , 92 ) and specificity of 51 % ( 95 % CI = 41 , 61 ) . This difference was not significant . In phase 2 , accuracy of nursing staff using the PJC-FRAT was lower . PJC-FRAT completion rates varied among disciplines over both phases : nurses and physiotherapists , > or = 90 % ; occupational therapists , > or = 82 % ; and medical officers , > or = 57 % . CONCLUSION The PJC-FRAT was practical and relatively accurate as a predictor of falls and a deployment instrument for falls prevention interventions , although continued staff education may be necessary to maintain its accuracy", "A prospect i ve cohort study was used to determine the reliability and validity of two fall risk assessment tools and nurses ' clinical judgement in predicting patient falls . The study wards comprised two aged care and rehabilitation wards within a 570 bed acute care tertiary teaching hospital in Western Australia . Instrument testing included test-retest reliability and calculations of sensitivity , specificity , positive predictive value , negative predictive value and accuracy . The test retest reliability of all methods was good . In this setting , the three methods of assessing fall risk showed good sensitivity but poor specificity . Also , all methods had limited accuracy , and overall , exhibited an inability to adequately discriminate between patient population s at risk of falling and those not at risk of falling . Consequently , neither nurses ' clinical judgement nor the fall risk assessment tools could be recommended for assessing fall risk in this clinical setting", "BACKGROUND AND PURPOSE Falls are a major complication in inpatient stroke rehabilitation . An important issue in preventive strategies is the early identification of those at risk . This study aim ed at assessing the fall-prediction accuracy of an easily administered fall risk index in stroke rehabilitation . METHODS A consecutive series of 135 patients admitted to a geriatric stroke rehabilitation unit was studied . A score on the Downton fall risk index was obtained from the admission assessment data and used as a predictive indicator of the risk of falls . The patients ' falls were prospect ively recorded during their rehabilitation stay . The correlation between falls and the predicted risk was assessed by means of survival analysis and a multiple regression analysis , adjusting for the time of observation . RESULTS The risk of falls as a function of the time observed was significantly greater among those predicted to be at high risk ( index score > or = 3 ) than among the others ( P = .009 , log-rank test ; odds ratio , 2.9 ) . Furthermore , the number of falls during rehabilitation stay was moderately correlated ( R = .57 ) with the fall risk index sum when adjusted as for the time of observation . The sensitivity of the fall prediction as to outcome was 91 % , whereas the specificity was limited to 27 % . CONCLUSIONS A moderately high correlation was found between the predicted and the observed risk of falls in stroke rehabilitation when the Downton fall risk index was used . However , a low specificity rate limits the accuracy of the prediction", "A retrospective case-control study related to falls was conducted at an 1,120-bed acute care tertiary hospital . The case ( fall ) sample consisted of 102 falls and 236 control ( nonfall ) charts during a 1-month period . An instrument developed by Hendrich ( 1988 ) was modified for use in the study . Demographic data and risk factors were recorded . Descriptive statistics included risk factor percentages for each sample and the corresponding univariate relative risks . Logistic regression was used to develop a multivariate risk factor model with seven risk factors . The significant risk factors were recent history of falls , depression , altered elimination patterns , dizziness or vertigo , primary cancer diagnosis , confusion , and altered mobility . The adjusted relative risks were converted to risk points to be used to assess a patient 's level of fall risk . Within the data set , a sensitivity of 77 % ( 79 of 102 ) and specificity of 72 % ( 169 of 236 ) were calculated . The model was cross-vali date d in a 1987 data set with a sensitivity of 83 % ( 59 of 71 ) and specificity of 66 % ( 106 of 161 )", "This large case/control study of fall and non-fall patients , in an acute care tertiary facility , was design ed to concurrently test the Hendrich Fall Risk Model . Cases and controls ( 355/780 ) were r and omly enrolled and assessed for more than 600 risk factors ( intrinsic/extrinsic ) . St and ardized instruments were used for key physical attributes as well as clinician assessment s. A risk factor model was developed through stepwise logistic regression . Two-way interactions among the risk factors were tested for significance . The best fitting model included 2 Log L chi square statistic as well as sensitivity and specificity values retrospectively . The result of the study is an easy to use vali date d Hendrich Fall Risk Model with eight assessment parameters for high-risk fall identification tested in acute care environments", "Accurate prediction of fall-prone hospitalized older adults may be integral to reducing falls . The STRATIFY , a simple 5-point falls prediction tool , was prospect ively vali date d on a Geriatric Assessment and Rehabilitation Unit as a one-time initial predictor of patients likely to fall . Sensitivity and specificity were lower than in the original British study . Introducing risk assessment s vali date d elsewhere on a patient care unit or on a hospital-wide scale requires caution", "BACKGROUND Patient falls constitute a major threat to health services ' ability to provide care . Previous studies confirm that nurses can identify patients at risk and that a preventative programme can reduce the rate of falls but few studies have been evaluated over time . AIMS AND OBJECTIVES A study was undertaken to test a Falls Prevention Programme in an acute medical area that was re-evaluated 5 years later to determine if the effects were sustainable . DESIGN The design included two groups of patients admitted before and after the programme . Variables such as staffing , equipment , environment and routines were controlled . However , because of ethical approval constraints , some variables such as age , mental status , mobility and gender were not . METHODS The programme included a risk assessment tool , a choice of interventions , a graphic that alerted others to ' at risk patients ' and simple patient and staff education . Data were collected using incident forms and a formula was used to calculate a rate of falls . A non-paired t-test compared rates and anova examined the relationship of age , gender , mobility and mental status on the incidence of falls . Control graphs determined the stability of the process . RESULTS The falls rate was significantly reduced . Control graphs demonstrate that the process achieved greater control with less variation . In the next 5 years the falls rate increased to preprogramme levels and control graphs demonstrated that the process was no longer controlled . Compliance with the programme had deteriorated . CONCLUSIONS The practice review considered skill mix , patient activity and acuity but provided no definitive answers to explain non-compliance . The implication s to nursing are discussed . RELEVANCE TO CLINICAL PRACTICE Clinicians are called to conduct more rigorous research into falls prevention but it may be more useful to direct research towards examining nursing work and increasing nurse autonomy in falls prevention", "OBJECTIVES To compare the effectiveness of four falls risk assessment tools ( STRATIFY , Downton , Tullamore , and Tinetti ) by using them simultaneously in the same environment . DESIGN Prospect i ve , open , observational study . SETTING Two acute medical wards admitting predominantly older patients . PARTICIPANTS One hundred thirty-five patients , 86 female , mean age+/-st and ard deviation 83.8+/-8.01 ( range 56 - 100 ) . MEASUREMENTS A single clinician prospect ively completed the four falls risk assessment tools . The extent of completion and time to complete each tool was recorded . Patients were followed until discharge , noting the occurrence of falls . The sensitivity , specificity , negative predictive accuracy , positive predictive accuracy , and total predictive accuracy were calculated . RESULTS The number of patients that the STRATIFY correctly identified ( n=90 ) was significantly higher than the Downton ( n=46 ; P sensitivity ( 68.2 % ) . The STRATIFY was also the only tool that could be fully completed in all patients ( n=135 ) , compared with the Downton ( n=130 ; P=.06 ) , Tullamore ( n=130 ; P=.06 ) , and Tinetti ( n=17 ; P time required to complete the STRATIFY tool ( average 3.85 minutes ) was significantly less than for the Downton ( 6.34 minutes ; P STRATIFY ( log rank P=.001 ) and Tullamore tools ( log rank P predicting falls over the first week of admission . The Downton ( log rank P=.46 ) and Tinetti tools ( log rank P=.41 ) did not demonstrate this characteristic . CONCLUSION Significant differences were identified in the performance and complexity between the four risk assessment tools studied . The STRATIFY tool was the shortest and easiest to complete and had the highest predictive value but the lowest sensitivity", "Forty-four patients aged 65 years and over who fell whilst in an acute hospital and 44 patients who did not fall during their hospital stay underwent structured medical examinations to identify factors associated with falling . The control subjects were matched for age ( + /- 3 years ) , sex , patient type , and primary diagnosis . The examination was based on established assessment s of posture , balance and gait , the musculoskeletal system , vision , cardiovascular status , and neurological function . Bivariate analyses revealed seven assessment measures that were significantly associated with falls : cognitive impairment , particularly impaired orientation ; evidence of previous cerebrovascular accident ; incoordination as measured clinical ly ; inability to perform the ' Get-up- and -go ' test , especially an inability to turn around after a 5-metre walk , and the use of psycho-active medications . Of these variables , impaired orientation , psycho-active drug use , evidence of stroke , and impaired performance in the ' Get-up- and -go ' test were included in a stepwise logistic regression which correctly classified 80 % of the patients into faller and non-faller groups . Falling was also related to the number of these identified risk factors . These findings suggest that a simple screening protocol , taking about 5 min to complete , can assist in the identification of patients at risk of falls whilst in hospital" ]

[ "Abstract Objective : To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children . Study design : R and omised double blind placebo controlled trial . Setting : Urban slums of Dhaka , Bangladesh . Participants and methods : 800 children aged 12 - 35 months were r and omly assigned to one of four intervention groups : 20 mg zinc once daily for 14 days ; 200 000 IU vitamin A , single dose on day 14 ; both zinc and vitamin A ; placebo . The children were followed up once a week for six months , and morbidity information was collected . Results : The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group . Zinc and vitamin A interaction had a rate ratio ( 95 % confidence interval ) of 0.79 ( 0.66 to 0.94 ) for the prevalence of persistent diarrhoea and 0.80 ( 0.67 to 0.95 ) for dysentery . Incidence ( 1.62 ; 1.16 to 2.25 ) and prevalence ( 2.07 ; 1.76 to 2.44 ) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group . The interaction term had rate ratios of 0.75 ( 0.46 to 1.20 ) for incidence and 0.58 ( 0.46 to 0.73 ) for prevalence of acute lower respiratory infection . Conclusions : Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery . Zinc was associated with a significant increase in acute lower respiratory infection , but this adverse effect was reduced by the interaction between zinc and vitamin A. What is already known on this topic Trials of vitamin A supplementation have failed to show a beneficial effect on morbidity in children Experimental studies have shown that , in the presence of zinc deficiency , vitamin A supplementation fails to reverse vitamin A deficiency Coexistence of deficiencies of zinc and vitamin A could be a reason for the failure of vitamin A supplementation , but data in humans are limited What this paper adds Combined zinc and vitamin A supplementation is more effective in reducing persistent diarrhoea and dysentery than either vitamin A or zinc alone Zinc alone increased respiratory illnesses , but interaction between zinc and vitamin A reduced this adverse", "OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation . MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost", "BACKGROUND R and omized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the st and ard treatment of pneumonia . OBJECTIVE We evaluated the effect of a moderate dose of vitamin A as an adjunct to st and ard antimicrobial treatment on the duration of respiratory signs in children with pneumonia . DESIGN Children , aged 2 - 59 mo , with pneumonia and weight-for-age , were r and omly assigned to receive 50,000 IU ( aged 2 - 12 mo ) or 100,000 IU ( aged > 12 - 59 mo ) vitamin A or a placebo . RESULTS Of the 287 children enrolled , 145 received vitamin A and 142 received placebo . No overall differences were observed between the 2 groups in the duration of signs of pneumonia . Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time ( in h ) to remission of respiratory signs ( beta = -3.57 , SE = 1.09 , P = 0.001 ) . Duration of clinical signs was less in children with basal serum retinol concentrations > 200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo ( 69.9 + /- 49.9 h compared with 131.3 + /- 143.9 h ; P = 0.049 ) . CONCLUSIONS Overall , we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged 5 y. However , a beneficial effect was seen in children with high basal serum retinol concentrations", "BACKGROUND Acute lower respiratory infection ( ALRI ) is a leading cause of childhood death . Zinc supplementation prevents ALRI . Vitamin A supplementation reduces childhood mortality , but its benefit concerning ALRI-specific mortality is unproven . OBJECTIVE The objective was to evaluate the effect of zinc and vitamin A on the clinical recovery of children with severe ALRI . DESIGN In a controlled trial with a factorial design , 153 children aged 2 - 24 mo who were hospitalized with severe ALRI were r and omly assigned to receive 10 mg zinc as acetate ( twice daily for 5 d ) plus vitamin A placebo , 10 000 micro g retinol equivalents vitamin A ( twice daily for 4 d ) plus zinc placebo , zinc plus vitamin A , or zinc and vitamin A placebos . The main outcome variable was the time for resolution of very ill status ; other outcomes were resolution of fever , tachypnea , and feeding difficulty . RESULTS Recovery rates from very ill status and from fever in zinc-treated boys were 2.6 times ( P = 0.004 ) and 3 times ( P = 0.003 ) those in non-zinc-treated children ; feeding difficulty and tachypnea were not significantly different between groups after an adjusted analysis . Recovery rates were not significantly different between groups on the basis of vitamin A treatment . At discharge , serum zinc was 6.06 micro mol/L higher ( P = 0.001 ) in the zinc-treated children , and serum retinol was 0.387 micro mol/L higher ( P = 0.001 ) in the vitamin A-treated children . CONCLUSION Zinc treatment significantly reduces duration of fever and very ill status in boys , but not in girls , with severe ALRI . Vitamin A treatment of children with severe ALRI had no significant beneficial effect", "Vitamin A supplementation of population s of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality , but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated . We conducted an individually r and omized , placebo-controlled , double-masked trial among 1,407 Indonesian preschool-age children , to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses . Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers . High dose vitamin A supplements increased the incidence of acute respiratory illnesses ( ARI ) by 8 % , and acute lower respiratory illnesses ( ALRI ) by 39 % . These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status ( rate ratio 1.83 , 95 % confidence interval 1.257 - 2.669 ) . In contrast , vitamin A tended to be protective of ALRI in chronically malnourished children ( rate ratio 0.71 , 95 % confidence interval 0.375 - 1.331 ) . There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease ( rate ratio 1.06 , 95 % confidence interval 0.920 - 1.225 ) . However , we found a significant interaction between supplementation and age : vitamin A increased the incidence of diarrhea in children adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting population s of preschool-age children for vitamin A supplementation", "Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries . We carried out a r and omized , double-blind , placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease . Six hundred eighty-seven children were r and omly assigned to receive either placebo or vitamin A [ 200 000 IU ( 60 mg retinol equivalents ) for children > 1 y of age and 100000 IU ( 30 mg retinol equivalents ) for infants ] on the day of admission and another dose on the following day . Of the 346 children in the vitamin A group , 13 died in the hospital , compared with 8 of 341 children in the placebo group ; the relative mortality was 1.63 ( 95 % CI : 0.67 , 3.97 ; P = 0.28 ) . The mean number of days of hospitalization was the same in both groups ( 4.2 d ) . There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age , sex , breast-feeding status , nutritional status at baseline , or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital . There were also no differences in the mean number of days of fever , rapid respiratory rate , or hypoxia , whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline . Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children", "Incidence , duration , and severity of diarrhea and respiratory symptoms were monitored weekly for 1 y in 15,419 children 6 - 60 mo of age in a r and omized , placebo-controlled , masked clinical trial conducted in southern India . Half the children received weekly doses of 8.7 mumol ( 2500 microgram ) vitamin A and 46 mumol ( 20 mg ) vitamin E ( treated ) and the other half , 46 mumol vitamin E ( control ) . Medical and ocular examinations and anthropometric measurements were obtained before and after 52 wk of intervention . Ocular examinations also were obtained after 26 wk . Supplements were delivered weekly from calibrated dispenser bottles by community health volunteers who also recorded each mother 's recall of daily morbidity of her child during the previous week . Baseline characteristics of treated and control subjects were similar and documented a prevalence of 11 % xerophthalmia and 72 % undernutrition . Weekly treatment with the low-dose vitamin A supplement did not influence the incidence , severity , or duration of diarrhea or respiratory infections and did not influence linear or ponderal growth", "OBJECTIVE To test the hypothesis that high-dose vitamin A supplements will enhance recovery of children hospitalized for the treatment of community-acquired pneumonia . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial of high-dose vitamin A supplements among children 3 months to 10 years of age ( N = 95 ) admitted to hospital with community-acquired pneumonia in Lima , Peru . Children received 100 000 IU of water-miscible vitamin A on admission to the hospital and an additional 50 000 IU the next day . Children > 1 year of age received 200 000 IU on admission and 100 000 IU the next day . RESULTS Children receiving vitamin A ( n = 48 ) had lower blood oxygen saturation ( the mean difference on day 3 in hospital was 1.1 % ) , higher prevalence rates of retractions ( 37 % in the vitamin A group vs 15 % in the placebo group on day 3 ) , auscultatory evidence of consolidation ( 28 % in the vitamin A group vs 17 % in the placebo group on day 3 ) , and were more likely to require supplemental oxygen ( 21 % in the vitamin A group vs 8 % in the placebo group on day 3 ) than children in the placebo group ( n = 47 ) . Adjustment for baseline severity of disease and nutritional status did not alter the association of vitamin A with increased clinical severity , although the difference in blood oxygen saturation was no longer statistically significant . No differences were seen in duration of hospitalization or in chest x-ray changes 14 days after admission . No deaths occurred , and toxicity of vitamin A was not seen . CONCLUSIONS This study indicates that high-dose vitamin A supplements cause modest adverse effects in children recovering from pneumonia and should not be used therapeutically in such patients unless there is clinical evidence of vitamin A deficiency or concurrent measles infection", "BACKGROUND Low-birth-weight ( LBW ) infants ( are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation , deficiency could result in pathological changes in the respiratory epithelium , with respiratory problems . OBJECTIVE A r and omised , double-blind , placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life . METHOD One hundred and thirty LBW infants ( gestational age The infants were r and omly allocated to a vitamin A or placebo group . Infants in the vitamin A group received 25,000 IU of vitamin A ( retinyl palmitate , Arovit drops , Roche , Basle , Switzerl and ) on study days 1 , 4 and 8 . Study day 1 was between 36 and 60 hours after delivery . Infants in the placebo group received a placebo ( formulated by Roche ) with a similar appearance and packed in the same dropper bottles as the vitamin A drops . RESULTS Vitamin A supplementation markedly improved serum retinol levels . After the last vitamin A dose , the vitamin A group had higher mean serum retinol concentrations than the placebo group ( 45.77 + /- 17.07 micrograms/dl v. 12.88 + /- 6.48 micrograms/dl , P = 0.0001 ) . There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation . Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen . There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life . There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation . The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6 % ( 7 hospitalisations ) in the vitamin A group compared with 7.4 % ( 2 hospitalisations ) in the placebo group ( log rank test P = 0.04 ) . After adjusting for risk factors this difference was no longer significant . CONCLUSION Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections . These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections", "OBJECTIVE To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection ( ALRI ) . DESIGN R and omised controlled , 2-by-2 factorial trial of supplementation with zinc and vitamin A. SETTING AND PARTICIPANTS 187 Indigenous children aged INTERVENTIONS Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU ( infants under 12 months ) , or 100 000 IU ; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg ( infants under 12 months ) or 40 mg . MAIN OUTCOME MEASURE Time to clinical recovery from fever and tachypnoea , duration of hospitalisation , and readmission for ALRI within 120 days . RESULTS There was no clinical benefit of supplementation with vitamin A , zinc or the two combined , with no significant difference between zinc and no-zinc , vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea , or duration of hospitalisation . Instead , we found increased morbidity ; children given zinc had increased risk of readmission for ALRI within 120 days ( relative risk , 2.4 ; 95 % CI , 1.003 - 6.1 ) . CONCLUSION This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas . Even in population s with high rates of ALRI and poor living conditions , vitamin A and zinc therapy may not be useful . The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population", "A beneficial effect of periodic vitamin A supplementation on childhood mortality has been demonstrated , but the effect on morbidity is less clear . We investigated the effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections ( ALRI ) in children from northeastern Brazil in a r and omised , double-blind , placebo-controlled community trial . 1240 children aged 6 - 48 months were assigned vitamin A or placebo every 4 months for 1 year . They were followed up at home three times a week , and data about the occurrence and severity of diarrhoea and ALRI were collected . Any child with cough and respiratory rate above 40 breaths per min was visited by a paediatrician . The overall incidence of diarrhoea episodes was significantly lower in the vitamin-A-supplemented group than in the placebo group ( 18.42 vs 19.58 x 10(-3 ) child-days ; rate ratio 0.94 [ 95 % Cl 0.90 - 0.98 ] ) . The benefit of supplementation was greater as regards severe episodes of diarrhoea ; the incidence was 20 % lower in the vitamin A group than in the placebo group ( rate ratio 0.80 [ 0.65 - 0.98 ] ) . With the st and ard definition of diarrhoea ( > or = 3 liquid or semi-liquid stools in 24 h ) the effect of vitamin A on mean daily prevalence did not reach significance , but as the definition of diarrhoea was made more stringent ( increasing number of stools per day ) , a significant benefit became apparent , reaching for diarrhoea with 6 or more liquid or semi-liquid stools in 24 h a 23 % lower prevalence . We found no effect of vitamin A supplementation on the incidence of ALRI . The reduction in severity of diarrhoea may be the most important factor in the lowering of mortality by vitamin A supplementation", "Background . Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of population s. The influence of malnutrition has not been examined in the majority of these trials . We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation . Methods . In a r and omized , double-blind , placebo-controlled field trial of 400 children , 6 to 36 months of age in a high And ean urban slum , half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks . Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections . Results . Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups . However , the incidence of acute lower respiratory infection ( ALRI ) was significantly lower in underweight ( weight-for-age z score [ WAZ ] . ALRI incidence was significantly higher in normal-weight ( WAZ > −2 SD ) supplement-treated children than in normal-weight children on placebo ( 9.8 vs 4.4 per 103 child-weeks ; rate ratio : 2.21 [ 95 % CI : 1.24–3.93 ] ) . By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo ( point estimate 0.148 [ 95 % CI : 0.034–0.634 ] ) . In contrast , risk of ALRI was higher in normal-weight supplement-treated children ( WAZ > −1 SD to mean ) than in normal-weight children on placebo in the same WAZ stratum ( point estimate : 2.51 [ 95 % CI : 1.24–5.05 ] ) . The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group ( point estimate : 0.26 [ 95 % CI : 0.06–1.00 ] ) . Conclusions . Weekly low-dose ( 10 000 IU ) vitamin A supplementation in a region of sub clinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over −1 SD . Protection from severe diarrhea was consistent with previous trials . Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI", "We carried out a r and omized , placebo‐controlled , double‐blinded trial to evaluate the effect on morbidity of high dose oral vitamin A , given on hospital admission to 592 children aged 1–59 months with moderate and severe pneumonia . Severely underweight children were not included , but 45 % were moderately underweight . The vitamin A and placebo groups were comparable in baseline characteristics . Four patients died . Among all of the surviving children , no differences were found regarding mean time for normalization of fever , respiratory rate and time of hospitalization . Stratification for moderate malnutrition , degree of pneumonia , age and sex revealed moderately malnourished vitamin A‐supplemented children to have a shorter time of hospitalization ( p= 0 . 04 ) , due to an effect in females aged > 12 months ( p= 0 . 02 ) and females with very severe pneumonia ( p= 0 . 048 ) . This study indicates that , in developing countries like Vietnam , supplementation with vitamin A in children with pneumonia could shorten the recovery rate in the ones that are undernourished , especially females > 1 y old", "Abstract Objective : To assess the impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhoea . Design : Double blind r and omised placebo controlled field trial . Setting : An urban slum area in New Delhi , India . Subjects—900 children aged 12 - 60 months attending a local health facility for acute diarrhoea of less than seven days ' duration r and omly allocated to receive vitamin A 200000 IU or placebo . Main outcome measures : Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance . Results : The incidence ( relative risk 1.07 ; 95 % confidence interval 0.92 to 1.26 ) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups . Among children aged 23 months or less there was a significant reduction in the incidence of measles ( relative risk 0.06 ; 95 % confidence interval 0.01 to 0.48 ) . The incidence of diarrhoea was also similar ( relative risk 0.95 ; 0.86 to 1.05 ) in the two groups . There was a 36 % reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months . Conclusions : Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea", "In a double blind design , 1520 children aged were individually r and omised in vitamin A and placebo group in slums of Ch and igarh . Children > 12 , 6 - 12 and received 200,000 , 100,000 , 500,000 I.U. of vitamin A respectively every 4 to 6 months during 15 months trial period . The prevalence of vitamin A deficiency was significantly reduced in vitamin A compared to placebo group during the follow-up period . In vitamin A group , incidence of diarrhoea and measles was significantly reduced but incidence of acute respiratory infections was not significantly different compared to control group . Risk of death was also significantly less in vitamin A group . Therefore , promotion of vitamin A rich diet or supplementation with synthetic vitamin A at 4 - 6 month interval should be a priority in population s where risk of vitamin A deficiency is high", "OBJECTIVE The objective of this study was to test the potential of routine vitamin A supplementation at admission to speed up recovery during hospitalization for acute lower respiratory tract infections ( ALRI ) and to decrease the levels of morbidity at 6 weeks after discharge . The study was conducted in the Central Hospital of Maputo ( CHM ) , Mozambique , from 1995 to 1997 . METHODS Children aged 6 - 72 months with ALRI admitted to the paediatric wards of the CHM were assigned to a supplementation group ( n = 71 , receiving 200000 IU of vitamin A ) or a control group ( n = 93 , receiving a placebo ) . RESULTS The prevalence of vitamin A deficiency was very high and similar between the two groups . The median number of inpatient days for the supplementation group was 3 , for the placebo group 4 days . On day 5 the rate of clinical discharge was 88.4 % ( n = 61/69 ) in the experimental intervention group and 73.9 % ( n = 65/88 ) in the placebo group ( P = 0.023 ) . CONCLUSION We found a statistically significant reduction in duration of admission among vitamin A-supplemented children with ALRI . This effect is in line with what is known about the role of vitamin A in human defence and immune mechanisms and with the serological evidence of the extent of vitamin A deficiency among the children in this trial", "OBJECTIVE To determine whether vitamin A supplementation at birth could reduce infant morbidity and mortality . STUDY DESIGN We conducted a placebo-controlled trial among 2067 Indonesian neonates who received either 52 micromol ( 50,000 IU ) orally administered vitamin A or placebo on the first day of life . Infants were followed up at 1 year to determine the impact of this intervention on infant mortality . A subgroup ( n = 470 ) was also examined at 4 and 6 months of age to examine the impact on morbidity . RESULTS Vital status was confirmed in 89 % of infants in both groups at 1 year . There were 19 deaths in the control group and 7 in the vitamin A group ( relative risk = 0.36 ; 95 % confidence interval = 0.16 , 0.87 ) . The impact was stronger among boys , infants of normal compared with low birth weight , and those of greater ponderal index . Among infants examined at 4 months of age , the 1-week period prevalence of common morbidities was similar for vitamin A and control infants . However , during this same 4-month period , 73 % and 51 % more control infants were brought for medical treatment for cough ( p = 0.008 ) and fever ( p = 0.063 ) , respectively . CONCLUSIONS Neonatal vitamin A supplementation may reduce the infant mortality rate and the prevalence of severe respiratory infection among young infants", "OBJECTIVE To test the efficacy of a high dose of vitamin A as adjuvant treatment for radiographically confirmed cases of acute lower respiratory tract infection ( ALRI ) . DESIGN R and omized , double-masked , placebo-controlled clinical trial . SETTING Two large urban hospitals in Guatemala City . PATIENTS Sequential sample of 263 children aged 3 to 48 months , identified in the emergency departments and admitted to the hospital . INTERVENTIONS Vitamin A ( 100,000 IU for children less than 1 year of age , and 200,000 IU for older children ) or placebo in addition to st and ard treatment for ALRI which included antibiotics , oxygen , bronchodilators , and intravenously administered solutions . MEASUREMENTS AND MAIN RESULTS The children were assessed every 8 hours . There were neither statistically nor clinical ly significant differences by treatment group in the rate of normalization in respiratory rate , oxygen saturation , temperature , or clinical score . Duration of hospitalization was not different by treatment group . Adverse outcomes ( mechanical ventilation , prolonged hospitalization , readmission or transfer , and death ) were equally distributed between the two groups . CONCLUSIONS Treatment with high doses of vitamin A over and above st and ard care for infants and children with non-measles-related ALRI is not efficacious for the current episode . Additional trials among population s in which vitamin A deficiency is more prevalent and severe should be considered", "Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality , the effects on morbidity are less clear . We have carried out two double-blind , r and omised , placebo-controlled trials of vitamin A supplementation in adjacent population s in northern Ghana to assess the impact on childhood morbidity and mortality . The Survival Study included 21,906 children aged 6 - 90 months in 185 geographical clusters , who were followed for up to 26 months . The Health Study included 1455 children aged 6 - 59 months , who were monitored weekly for a year . Children were r and omly assigned either 200,000 IU retinol equivalent ( 100,000 IU under 12 months ) or placebo every 4 months ; r and omisation was by individual in the Health Study and by cluster in the Survival Study . There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections ; of the symptoms and conditions specifically asked about , only vomiting and anorexia were significantly less frequent in the supplemented children . Vitamin-A-supplemented children had significantly fewer attendances at clinics ( rate ratio 0.88 [ 95 % CI 0.81 - 0.95 ] , p = 0.001 ) , hospital admissions ( 0.62 [ 0.42 - 0.93 ] , p = 0.02 ) , and deaths ( 0.81 [ 0.68 - 0.98 ] , p = 0.03 ) than children who received placebo . The extent of the effect on morbidity and mortality did not vary significantly with age or sex . However , the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters ( 0.66 [ 0.47 - 0.92 ] , p = 0.02 ) ; mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters , but not significantly so . Improving the vitamin A intake of young children in population s where xerophthalmia exists , even at relatively low prevalence , should be a high priority for health and agricultural services in Africa and elsewhere", "Abstract Objective : To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the st and ard treatment for childhood pneumonia . Design : A r and omised , double blind , placebo controlled trial . Setting : Study children were recruited at a public hospital in Recife , north east Brazil , an area of marginal vitamin A deficiency . Subjects : 472 children aged 6 to 59 months with clinical diagnosis of pneumonia . Interventions : 200 000 IU ( infants ) or 400 000 IU ( 1 - 4 year olds ) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses , in addition to the st and ard treatment . Main outcome measures : Duration of the episode and incidence of adverse outcomes . Results : The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes . Children who received vitamin A , however , were less likely to have fever by day 3 ( P=0.008 ) and were 29 % less likely to fail to respond to the first line antibiotic ( P=0.054 ) . Conclusion : There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode . Key messages Pneumonia is a leading cause of childhood mortality in developing countries Vitamin A supplementation has no impact on mortality from pneumonia even though it reduces overall mortality Treatment of measles pneumonia with vitamin A reduces case fatality and severity of disease This study showed that vitamin A treatment has no impact on the recovery from non-measles pneumonia , despite some suggestion that severely affected patients may benefit The addition of vitamin A for treatment protocol s for childhood pneumonia is not recommended for clinical cure , although it maybe a useful contact to improve vitamin A" ]

[ "We selected r and omly a consecutive series of 162 patients requiring hip replacement to receive either a cementless , hemispherical , modular , titanium acetabular cup or a cemented , all-polyethylene cup . These replacements were performed by two surgeons in four general hospitals . The same surgical technique was used and a 26 mm metal-head femoral component was used in every case . After exclusions , 115 hips were studied for differences in rates of wear and osteolysis . The mean clinical follow-up was eight years and the mean radiological follow-up , 6.5 years . The cementless cups wore at a mean rate of 0.15 mm per year and the cemented cups at 0.07 mm per year . This difference was significant ( p cementless cups wear more than cemented cups", "We studied prospect ively the long-term results of the Charnley Elite-Plus femoral stem in 184 consecutive young patients ( 194 hips ) . There were 130 men and 54 women with a mean age of 49.1 years ( 21 to 60 ) . The predominant diagnosis was osteonecrosis of the femoral head ( 63.6 % , 117 patients ) . Clinical and radiological evaluation was undertaken at each follow-up . The mean follow-up was 11.2 years ( 10 to 12 ) . The mean pre-operative Harris hip score was 43.4 ( 12 to 49 ) which improved to 91 ( 59 to 100 ) at the final follow-up . The survival of the femoral stem at 12 years was 99 % with revision as the end-point . The mean annual linear wear of the polyethylene liner was 0.17 mm ( 0.13 to 0.22 ) . The prevalence of acetabular osteolysis was 10.8 % ( 21 hips ) and osteolysis of the calcar femorale 12.9 % ( 25 hips ) . A third-generation cementing technique , accurate alignment of the stem and the use of a 22 mm zirconia head were important factors in the prevention of aseptic loosening of the Elite Plus femoral stem in these high-risk young patients", "Background : We previously reported our two and five‐year results of arthroplasty with the Porous Coated Anatomic total hip prosthesis . We now report on the performance of this prosthesis at ten to fourteen years . Methods : The results of 311 total hip replacements in which a Porous Coated Anatomic prosthesis was inserted without cement in 279 patients were analyzed prospect ively . The average age of the patients at the time of the replacement was sixty-one years ( range , twenty to eighty‐one years ) . Sixty‐four patients ( seventy-six hips ) died postoperatively . Forty‐five patients ( forty‐seven hips ) were lost to follow‐up , and four were excluded because of their medical condition . One hundred and sixty‐eight patients ( 187 hips ) were followed for ten to fourteen years ( average , twelve years ) . Seventeen of those patients ( seventeen hips ) had a revision . Results : The overall survival rate ( with any revision as the end point ) was 90.0 % ± 5.4 % at fourteen years , with an average Harris hip score of 85 ± 14 points . The prevalence of thigh pain was 36 % ( fifty-six of 157 ) in the late period ( more than ten years postoperatively ) . Radiographs showed stable fixation , with bone ingrowth , of 83 % ( 130 ) of the 156 acetabular components and 88 % ( 137 ) of the 156 femoral components at the latest follow‐up evaluation . Men had a significantly higher rate of femoral osteolysis than did women ( p The rates of acetabular and femoral osteolysis associated with 32‐mm femoral heads ( 49 % [ twenty-three ] of forty-seven and 70 % [ thirty-three ] of forty-seven , respectively ) were significantly higher ( p including thigh pain and an increasing prevalence of osteolysis with time . Revision because of aseptic loosening was related more to the thickness of the polyethylene liner than to the size of the femoral head . Femoral heads with a 32-mm diameter did not increase the risk for revision provided that an adequate thickness of polyethylene had been used", "Background Even though there are multiple studies documenting the outcome of the Charnley low-friction arthroplasty as well as abundant studies on uncemented arthroplasties , there is a dearth of comparative studies of the uncemented acetabular component and a cemented component . In this study we aim ed to document the long-term clinical and radiographic outcome as well as component survival in a r and omized controlled trial . Material s and methods Two hundred fifteen patients ( 240 hips ) were r and omly allocated to receive a cemented Charnley cup or uncemented Duraloc 1200 cup . All patients received cemented Charnley stems and were evaluated clinical ly and radiographically after 6 months , and 2 , 5 , and 10 years . Results Harris Hip Scores improved from 48.3 [ 95 % confidence interval ( CI ) 45.0–51.6 ] to 90.2 [ 95 % CI 87.9–92.6 ] in the Charnley group and from 49.3 [ 95 % CI 86.9–91.3 ] in the Duraloc group at 6 months . After 10 years , the Charnley group ’s Harris Hip Score was 89.8 [ 95 % confidence interval ( CI ) 87.0–92.6 ] , and the Duraloc group ’s score was 87.3 ( 95 % CI 84.1–90.6 ) . In the radiographic analysis after 10 years , there was no statistical difference in the prevalence of radiographic signs of loosening . Nine cups were revised in the Charnley group , and five cups were removed in the Duraloc group . The difference was not statistically significant . There was no statistical difference between the cups when aseptic loosening was the end-point , nor in survival analyses . Conclusions There is no statistically significant difference in clinical or radiological outcome between the Charnley cup and the Duraloc after 10 years , and no difference in implant survival after 12–14 years . The uncemented Duraloc cup is as good as the cemented Charnley cup after 10 years", "Abstract : The purpose of this study was to up date the results of a prospect i ve series of primary cementless total hip arthroplasties after a minimum of fifteen years of follow-up . It is one of the first studies of cementless total hip arthroplasties followed for a minimum of fifteen years . One hundred consecutive Porous Coated Anatomic ( PCA ) total hip replacements were implanted between October 1983 and January 1986 . Fifty-five patients ( sixty-four hips ) that were alive at a minimum of fifteen years postoperatively are the focus of the present study . At this time of follow-up , at an average of 15.6 years ( range , fifteen to seventeen years ) after the total hip arthroplasty , 17 % ( seventeen hips ) of the entire cohort and 23 % ( fifteen hips ) of the living cohort had undergone revision because of loosening of the acetabular component or osteolysis . Seven percent ( seven hips ) of the entire cohort and 6 % ( four hips ) of the living cohort had undergone revision for loosening of the femoral component or osteolysis . Only four femoral stems had been revised for isolated loosening ( without osteolysis).The PCA femoral component proved to be durable at a minimum of fifteen years postoperatively , while the acetabular component was less durable . Level of Evidence : Therapeutic study , Level IV ( case series [ no , or historical , control group ] ) . See Instructions to Authors for a complete description of levels of evidence", " We enrolled 98 patients ( 107 hips ) with a mean age of 47 years ( SD 8.6 ) into a prospect i ve study of the Madreporic Lord THR ; 34 hips had primary and 73 secondary osteoarthritis . After ten years , the survival rate using revision as the endpoint for failure was 70 % ( + /-9 ) for the cup and 98 % ( + /-0.3 ) for the stem . The combined clinical and radiological survival rates were 46 % ( + /-11 ) and 81 % ( + /-10 ) , respectively . Osteoporosis due to stress-shielding was observed in the proximal femur . Hips with radiologically dense bone postoperatively showed the most pronounced bone loss . We recommend continued radiological follow-up of patients with this type of implant to allow revision to be performed before there is severe bony destruction of the pelvis", " In a prospect i ve study , 93 unselected consecutive uncemented hip arthroplasties were performed in 80 patients using the titanium-coated RM acetabular component and the CLS femoral component . The mean age of the patients at operation was 52 years ( 28 to 81 ) . None were lost to follow-up . In the 23 patients who had died ( 26 hips ) only one acetabular component had been revised . In the 57 living patients ( 67 hips ) , 13 such revisions had been performed . Of the 14 revisions , seven were for osteolysis , five for loosening and two for infection . Survival analysis of this implant showed a total probability of survival of 83 % ( 95 % confidence interval 73 to 90 ) , with all revisions as the endpoint , and a probability of 94 % ( 95 % confidence interval 87 to 98 ) with revision for aseptic loosening as the endpoint , indicating reliable long-term fixation of the titanium-coated RM acetabular component", "The purpose of the current study was to up date the results of a prospect i ve , single-surgeon series of primary Charnley total hip arthroplasties performed with cement . This investigation is one of the first studies in which hips treated with total hip arthroplasty with cement were followed for a minimum of thirty years . Twenty-seven patients ( thirty-four [ 10.3 % ] of the hips in the initial study group ) were alive at a minimum of thirty years postoperatively . These patients served as the focus of the present study . Revision because of aseptic loosening of the acetabular component was performed in 7.3 % ( twenty-three ) of the hips from the original study group ( excluding those revised because of infection or dislocation ) and 26 % ( eight ) of the hips in the living cohort . Revision because of aseptic loosening of the femoral component was performed in 3.2 % ( ten ) of the hips from the original study group ( excluding those revised because of infection or dislocation ) and 10 % ( three ) of the hips in the living patients . Since the twenty-five-year review , three hips were revised ( one because of acetabular loosening , one because of femoral loosening , and one because of instability ) . This end- result study demonstrated the remarkable durability of cemented Charnley total hip replacements over a span of three decades , with 88 % of the original prostheses intact at the time of the final follow-up or at the patient 's death", "There have been comparatively few studies of the incidence of osteolysis and the survival of hybrid and cementless total hip replacements ( THRs ) in patients younger than 50 years of age . We prospect ively review ed 78 patients ( 109 hips ) with a hybrid THR having a mean age of 43.4 years ( 21 to 50 ) and 79 patients ( 110 hips ) with a cementless THR with a mean age of 46.8 years ( 21 to 49 ) . The patients were evaluated clinical ly using the Harris hip score , the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis score and the University of California , Los Angeles ( UCLA ) activity score . Radiographs and CT scans were assessed for loosening and osteolysis . The mean follow-up was for 18.4 years ( 16 to 19 ) in both groups . The mean post-operative Harris hip scores ( 91 points versus 90 points ) , the mean WOMAC scores ( 11 points versus 13 points ) and UCLA activity scores ( 6.9 points versus 7.1 points ) were similar in both groups . The revision rates of the acetabular component ( 13 % versus 16 % ) and the femoral component ( 3 % versus 4 % ) , and the survival of the acetabular component ( 87 % versus 84 % ) and the femoral component ( 97 % versus 96 % ) were similar in both groups . Although the long-term fixation of the acetabular metallic shell and the cemented and cementless femoral components was outst and ing , wear and peri-acetabular osteolysis constitute the major challenges of THR in young patients", "Hydroxyapatite ( HA ) particles have long been suspected to disintegrate from implant surfaces , become entrapped in joint spaces of orthopaedic bearing couples , and start a cascade leading to progressive polyethylene ( PE ) wear , increased osteolysis , and aseptic loosening . We compared cup revision at 15 years ’ followup in a r and omized group of patients with 26 cementless THA components with titanium ( Ti ) versus first-generation HA coating . We also assessed radiographic PE wear and osteolysis to the 12-year followup or end point revision at a minimum of 5 years ( mean , 10.9 years ; range , 5–12.6 years ) . Two Ti-coated cups ( 17 % ) and eight HA-coated cups ( 57 % ) were revised at 15 years ’ followup . Femoral head penetration rate was 0.46 mm/year ( st and ard deviation , 0.26 ) with the HA-coated cups ( n = 12 ) and 0.38 mm/year ( st and ard deviation , 0.14 ) with the Ti-coated cups ( n = 10 ) ; we observed a wide variance of linear wear with the HA-coated cups . We also observed a positive association between high wear rate and revision , and between a high volume of osteolysis and revision . Our findings suggest inferior survival of medium-thickness spray-dried HA-coated cups with individual cases of excessive PE wear and premature cup failure . These findings apply to first-generation modular cups and may not apply to other cup design s and new HA-coating technologies . Level of Evidence : Level III , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "Background Total hip arthroplasty ( THA ) has been associated with high survival rates , but debate remains concerning the best fixation mode of THA . Questions / purpose sWe conducted a r and omized controlled trial ( RCT ) with 250 patients with a mean age of 64 years between October 1987 and January 1992 to compare the results of cementless and cemented fixation . Patients and Methods Patients were evaluated for revision of either of the components . One hundred twenty-seven patients had died ( 51 % ) and 12 ( 4.8 % ) were lost to followup . The minimum 17-year followup data ( mean , 20 years ; range , 17–21 years ) for 52 patients of the cementless group and 41 patients of the cemented group were available for evaluation . Results Kaplan-Meier survivorship analysis at 20 years revealed lower survival rates of cemented compared with cementless THA . The cementless tapered stem was associated with a survivorship of 99 % . Age younger than 65 years and male gender were predictors of revision surgery . Conclusions The efficacy of future RCTs can be enhanced by r and omizing patients in specific patient cohorts stratified to age and gender in multicenter RCTs . Including only younger patients might improve the efficacy of a future RCT with smaller sample sizes being required . A minimum 10-year followup should be anticipated , but this can be expected to be longer if the difference in level of quality between the compared implants is smaller . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "BACKGROUND The mechanisms leading to aseptic loosening of a total hip replacement are not fully understood . A fibrous tissue interface can be present around the implant . Hypothetically , component micromovements can compress this interface and cause increased fluid pressure according to biphasic models . We tested the hypothesis that compression of a fibrous membrane with or without the presence of high-density polyethylene particles leads to bone degradation . METHODS A titanium implant was inserted in forty-five rabbit tibiae , and , after osseous integration was achieved , a fibrous tissue interface was generated . The animals were r and omized to undergo a sham operation , treatment with compression of the fibrous membrane , treatment with high-density polyethylene particles , or treatment with both compression and particles . Morphometric analysis of the surrounding bone was performed on cryostat sections after Giemsa staining and staining of tartrate-resistant acid phosphatase activity . RESULTS Forty specimens were available for analysis ; five tibiae with an infection were excluded . After nine weeks , the controls showed vital bone , whereas the specimens treated with compression showed necrosis of bone and replacement of bone by cartilage in a discontinuous layer ( p high-density polyethylene particles caused replacement of bone by fibrous tissue ( p necrosis or cartilage formation . Compression combined with the presence of high-density polyethylene particles caused bone necrosis and loss of bone with replacement by cartilage and fibrous tissue ( p study in rabbits , fibrous membrane compression led to bone necrosis and cartilage formation , possibly because of fluid pressure or fluid flow , whereas the presence of high-density polyethylene particles led to the loss of bone with replacement of bone by fibrous tissue . Cartilage formation may be a protective response to fluid pressure and /or fluid flow . Fibrous membrane compression may play an important role in the early stages of loosening of a total hip replacement", " In a matched-pair study of primary total hip arthroplasty , 45 all-polyethylene cemented acetabular components were compared with 45 cementless , hemispheric , titanium acetabular components . At 9 to 12 years , 1 of the cemented acetabular components was revised for aseptic loosening , and 14 ( 31 % ) were radiographically loose . Nine ( 20 % ) cemented acetabular components had pelvic osteolysis . In the cementless acetabular component group , 2 well-fixed components were revised . No components were radiographically loose , and 3 ( 7 % ) had pelvic osteolysis . Thirty-eight ( 97 % ) of the patients in each group were satisfied with the surgery . The clinical results of the cemented and cementless components were excellent . The cementless components had less loosening ( P < .001 ) than the cemented components", "Introduction We conducted a prospect i ve study to evaluate the long-term results after Corin C-Fit uncemented total hip arthroplasty in young patients with hydroxyapatite or porous coated components . Material s and methods We prospect ively followed 36 patients ( 38 hips ) who had Corin C-Fit uncemented total hip arthroplasties by eight experienced consultant surgeons at two centres . The acetabular and femoral components were hydroxyapatite or porous coated . Results The overall 10-year survival rate for the Corin C-Fit arthroplasty was 43 % . The 10-year survivorship for the femoral implant was 56 % and for the acetabular component 59 % . Conclusion The evidence presented in this study suggests that the Corin C-Fit uncemented total hip arthroplasty has one of the highest mid- and long-term failure rates for both femoral and acetabular components in the literature . We believe this implant should not be used and patients who have had this form of total hip arthroplasty should be kept under regular review" ]

[ "Several authors have demonstrated the pivotal role of proinflammatory cytokines in inducing progressive cartilage degradation and secondary inflammation of the synovial membrane in osteoarthritis ( OA ) . It has recently been established that tumor necrosis factor (TNF)-alpha plays a well-defined role in the pathophysiology of inflammatory joint diseases and that binding to circulating soluble TNF-alpha receptors can inactivate it . We investigated the influence of mud pack treatment , which is able to diminish TNF-alpha serum values , on specific TNF receptor ( sTNF-R ) levels . Thirty-six patients with OA were enrolled and r and omized into two groups . Group A underwent mud pack treatment and group B underwent thermal bath treatment . A group of 20 healthy untreated subjects was used as a control . Blood sample s were collected at baseline and after treatment , and assays of sTNF-R55 and sTNF-R75 were performed in both groups . We found small changes in sTNF-Rs serum values but these were not statistically significant . sTNF-R55 serum values decreased by 0.4 % after the therapy in group A , while in group B the decrease was -17.7 % . sTNF-R75 was reduced by -21.17 % in group A and by -10.6 % in group B. In conclusion , through its thermic and ant/inflammatory activity mud pack treatment shows complex interaction with the most common factors of inflammatory and cartilage degradation . Our results suggest that the thermic component of this natural treatment is mainly involved in modulating inflammatory reaction and cartilage damage through binding of the circulating TNF , which controls the activation of the cells responsible for the production of proinflammatory cytokines", "We aim ed to evaluate the effectiveness of balneotherapy in fibromyalgia management . Fifty women with fibromyalgia under pharmacological treatment were r and omly assigned to either the balneotherapy ( 25 ) or the control ( 25 ) group . Four patients from the balneotherapy group and one patient from the control group left the study after r and omization . The patients in the balneotherapy group ( 21 ) had 2 thermomineral water baths daily for 2 weeks in Tuzla Spa Center . The patients in the control group ( 24 ) continued to have their medical treatment and routine daily life . An investigator who was blinded to the study arms assessed the patients . All patients were assessed four times ; at the beginning of the study , at the end of the 2nd week , the 1st month , and the 3rd month after balneotherapy . Outcome measures of the study were pain intensity , Fibromyalgia Impact Question naire ( FIQ ) , Beck Depression Inventory ( BDI ) , patient ’s global assessment , investigator ’s global assessment , SF-36 scores , and tender point count . Balneotherapy was found to be superior at the end of the cure period in terms of pain intensity , FIQ , Beck Depression Inventory , patient ’s global assessment , investigator ’s global assessment scores , and tender point count as compared to the control group . The superiority of balneotherapy lasted up to the end of the 3rd month , except for the Beck Depression Inventory score and the investigator ’s global assessment score . Significant improvements were observed in PF , GH , and MH subscales of SF-36 during the study period in the balneotherapy group ; however , no such improvement was observed in the control group . Balneotherapy was superior only in VT subscale at the end of therapy and at the end of the third month after the therapy as compared to the controls . It was concluded that balneotherapy provides beneficial effects in patients with fibromyalgia", "The purpose of this study was to investigate the clinical effects of balneotherapy in the treatment of Fibromyalgia Syndrome ( FMS ) and to determine if balneotherapy influences serum levels of inflammation markers , IL-1 , PGE2 and LTB4 . 24 primary fibromyalgia female patients diagnosed according to American College of Rheumatology criteria were included to the study . Their ages ranged between 33 and 55 years . FMS patients were r and omly assigned in two groups as , group 1 ( n = 12 ) and group 2 ( n = 12 ) . Group 1 received 20-min bathing , once in a day for five days per week . Patients participated in the study for 3 weeks ( total of 15 sessions ) in Denizli . Group 2 did not receive balneotherapy . FMS patients were evaluated by tenderness measurements ( tender point count and algometry ) , Visual Analogue Scale , Beck ’s Depression Index , Fibromyalgia Impact Question naire . Ten healthy women recruited group three as the controls . Serum PGE2 , LTB4 and IL1-α levels were measured in all three groups . The biochemical measurements and clinical assessment s were performed before and at the end of general period of therapy . Statistically significant alterations in algometric score , Visual Analogue score , Beck ’s Depression Index and PGE2 levels ( P ) , numbers of tender points ( P and Fibromyalgia Impact Question naire score ( P balneotherapy between group 1 and 2 . Mean PGE2 level of FMS patients were higher compared to healthy control group ( P After balneotherapy IL-1 and LTB4 significantly decreased in group 1 ( P balneotherapy is an effective choice of treatment in patients with FMS relieving the clinical symptoms , and possibly influencing the inflammatory mediators", "Multidisciplinary treatment has proven to be the best therapeutic option to fibromyalgia ( FM ) and physiotherapy has an important role in this approach . Considering the controversial results of electrotherapy in this condition , the aim of this study was to assess the effects of combined therapy with pulsed ultrasound and interferential current ( CTPI ) on pain and sleep in FM . Seventeen patients fulfilling FM criteria were divided into two groups , CTPI and SHAM , and su bmi tted to pain and sleep evaluations . Pain was evaluated by body map ( BM ) of the painful areas ; quantification of pain intensity by visual analog scale ( VAS ) ; tender point ( TP ) count and tenderness threshold ( TT ) . Sleep was assessed by inventory and polysomnography ( PSG ) . After 12 sessions of CTPI or SHAM procedure , patients were evaluated by the same initial protocol . After treatment , CTPI group showed , before and after sleep , subjective improvement of pain in terms of number ( BM ) and intensity ( VAS ) of painful areas ( P in TP count and increase in TT ( P Subjective sleep improvements observed after CTPI treatment included decrease in morning fatigue and in non‐refreshing sleep complaint ( P decrease in sleep latency ( P percentage of stage 1 ( P increase in the percentage of slow wave sleep ( P and in sleep cycle count ( P ) . Decrease in arousal index ( P ) , number of sleep stage changes ( P and wake time after sleep onset ( P regarding pain or sleep parameters were verified after SHAM procedure . This study shows that CTPI can be an effective therapeutic approach for pain and sleep manifestations in FM", "Fibromyalgia ( FM ) is a nonarticular rheumatological syndrome associated with diverse clinical and psychological features . One of the major complaints in FM is reduced pain tolerance , especially in tender points ( TP ) for which patients derive significant benefit from nonsteroidal antiinflammatory drugs or corticosteroids . Patients with FM also have altered reactivity of the hypothalamic pituitary adrenal ( HPA ) axis where the predominant feature is reduced containment of the stress response system through diminished adrenocortical output and feedback resistance . Our results show that mud packs together with antidepressant treatment are able to influence the HPA axis , stimulating increased levels of adrenocorticotropic hormone , cortisol and beta-endorphin serum levels . The discharge of corticoids in the blood and the increase in beta-endorphin serum levels are followed by a reduction in pain symptoms , which is closely related to an improvement in disability , depression and quality of life . It seems that the synergic association between a pharmacological treatment ( trazodone ) and mud packs acts by helping the physiological responses to achieve homeostasis and to rebalance the stress response system . To clarify and optimize the effectiveness of this synergic association , studies involving a larger number of FM patients and a different pharmacological treatment are needed", "Objective The aim of this study was to compare pool-based exercise and balneotherapy in fibromyalgia syndrome ( FMS ) patients . Methods Fifty female patients diagnosed with FMS according to the American College of Rheumatism ( ACR ) criteria were r and omly assigned to two groups : group 1 ( n=25 ) with pool-based exercise , and in group 2 ( n=25 ) balneotherapy was applied in the same pool without any exercise for 35 min three times a week for 12 weeks . In both groups , pre- ( week 0 ) and post-treatment ( weeks 12 and 24 ) evaluation was performed by one of the authors , who was blind to the patient group . Evaluation parameters included pain , morning stiffness , sleep , tender points , global evaluation by the patient and the physician , fibromyalgia impact question naire , chair test , and Beck depression inventory . Statistical analysis was done on data collected from three evaluation stages . Results Twenty-four exercise and 22 balneotherapy patients completed the study . Pretreatment ( week 0 ) measurements did not show any difference between the groups . In group 1 , statistically significant improvement was observed in all parameters ( P chair test at both weeks 12 and 24 . In group 2 , week 12 measurements showed significant improvement in all parameters ( P chair test and Beck depression inventory . Week 24 evaluation results in group 2 showed significant improvements in pain and fatigue according to visual analogue scale ( VAS ) , 5-point scale , number of tender points , algometric and myalgic scores , and patient and physician global evaluation ( P morning stiffness , sleep , fibromyalgia impact question naire ( FIQ ) , chair test , and Beck depression inventory parameters in this group . Comparison of the two groups based on the post-treatment ( weeks 12 and 24 ) percent changes and difference scores relative to pretreatment ( week 0 ) values failed to show a significant difference between the groups for any parameter except Beck depression inventory ( P pool-based exercise had a longer-lasting effect on some of the FMS symptoms , but statistical analysis failed to show a significant superiority of pool-based exercise over balneotherapy without exercise . While we believe that exercise is a gold st and ard in FMS treatment , we also suggest in light of our results that balneotherapy is among the valid treatment options in FMS , and further research regarding the type and duration of the exercise programs is necessary", "OBJECTIVE It is a traditional practice in the Alpine region of Trentino and Alto Adige ( Italy ) to use phytothermotherapeutic treatment with fermenting grass ( \" hay baths \" ) for rheumatic diseases . However , despite its long history and popularity , a clinical validation of the efficacy and tolerability of the treatment has yet to be found in current literature . Fibromyalgia syndrome ( FMS ) is characterised by generalised musculoskeletal pain , high tender point counts , sleep disturbance , fatigue , headaches , irritable bowel syndrome , frequent psychological distress and depressed mood . There is no st and ard therapy regime for FMS and the variety of medical treatments used have given limited benefits . The aim of this study was to assess the efficacy and tolerability of a cycle of phytothermotherapy through a single-blind , controlled , r and omised trial , in patients with primary FMS . METHODS Fifty-six patients with primary FMS according to the ACR criteria were r and omly allocated to two groups : 30 were su bmi tted to phytothermotherapy at the thermal resort of Garniga Terme ( Trento , Italy ) and the other 26 were considered as controls . All patients were evaluated by FIQ , Tender Points Count , HAQ and AIMS 1 at baseline , after 10 days , then after 12 and 24 weeks . RESULTS Patients su bmi tted to phytothermotherapy showed visible and significant improvement of all evaluation parameters at the end of the treatment , which persisted during the follow-up period . No significant difference was found in the control group . Regarding the tolerability , none of the patients presented side effects . CONCLUSIONS Our results suggest the efficacy and the tolerability of phytothermotherapy in patients with primary FMS", "The efficacy of balneotherapy in fibromyalgia syndrome ( FS ) has been well demonstrated , while controlled studies using mud packs are lacking . We performed a r and omized clinical trial to evaluate the effects and the tolerability of mud-bath treatment in FS patients , who are poor responders to pharmacological therapy . Eighty patients with primary FS , according to ACR criteria , were r and omly allocated to two groups : 40 were su bmi tted to a cycle of 12 mud packs and thermal baths , and 40 were considered as controls . At baseline , after thermal treatment and after 16 weeks , patients were evaluated by FIQ , tender points count , VAS for “ minor ” symptoms , AIMS 1 and HAQ . Control patients were assessed at the same time periods . A significant improvement of all evaluation parameters after mud-bath therapy and after 16 weeks was observed . Mud packs were well tolerated and no drop-outs were recorded . Our results suggest the efficacy and the tolerability of mud-bath treatment in primary FS", "OBJECTIVE To measure , and seek clinical correlates with , levels of substance P ( SP ) in the cerebrospinal fluid ( CSF ) of fibromyalgia syndrome ( FMS ) patients . METHODS CSF from 32 FMS patients and 30 normal control subjects was tested for SP by radioimmunoassay . Clinical measures included tender point examination and st and ardized question naires . RESULTS CSF SP levels were 3-fold higher in FMS patients than in normal controls ( P tenderness found on examination . CONCLUSION SP is significantly elevated in FMS CSF , but other abnormalities must exist in FMS to more fully explain the symptoms", "OBJECTIVE To assess the responsiveness of the Fibromyalgia Impact Question naire ( FIQ ) , patient ratings of pain intensity , number of tender points , and total tender point pain intensity score to perceived changes in clinical status in patients with fibromyalgia ( FM ) . METHODS Using data from a r and omized placebo controlled study evaluating efficacy of magnetic therapy in patients with FM , the ability of primary outcomes to detect clinical ly meaningful changes over a 6 month period was assessed by : ( 1 ) degree of association between outcome change scores and patient global ratings of symptom change ( Spearman rank-order correlations ) ; ( 2 ) ability of these scores to discriminate among groups of patients whose perceived health status had changed to varying degrees ( ANOVA ) ; ( 3 ) ability of these scores , individually and jointly , to discriminate between patients who had reported improvement and those who did not ( logistic regression ) ; ( 4 ) effect size , st and ardized response mean , and Guyatt 's statistic were calculated to quantify responsiveness . RESULTS Correlations showed the outcome measures were moderately responsive to perceived symptomatic change . For FIQ , pain intensity ratings and number of tender points , differences in change scores between globally improved and unchanged groups and between globally improved and worsened groups were significant ; for total tender point pain intensity , the globally improved differed from worsened group . FIQ outperformed the other measures in discriminating between patients who reported improvement from those who did not . Summary statistics were consistent with discriminatory analyses , indicating the measures were sensitive to improvement , but relatively unresponsive to decline . CONCLUSION The FIQ was the most responsive measure to perceived clinical improvement and we recommend its inclusion as a primary endpoint in FM clinical trials", "Objective : The aim of the present study is to evaluate the effectiveness of spa therapy in the management of fibromyalgia . Methods : Thirty women with fibromyalgia were r and omly assigned to either a spa therapy group or a control group . The spa therapy group ( n = 16 ) had spa treatment for 2 weeks in addition to their medical treatment . The control group ( n = 14 ) continued to have their medical treatment and /or daily exercises . An investigator who was blinded for the intervention assessed all the patients for 9 months . Improvements in Fibromyalgia Impact Question naire ( FIQ ) , pain and number of tender points were primary outcomes . Secondary outcome measures were improvement in sleep disturbance , fatigue , gastrointestinal symptoms , anxiety , Beck Depression Inventory and patient ’s global evaluation . Results : the spa group was found to be superior to the control group at the end of intervention in terms of FIQ , pain , tender point count , fatigue and patients ’ global assessment . This superiority remained for 6 months in FIQ , 1 month in pain and tender point count . Conclusion : It was concluded that the addition of spa therapy to medical therapy has both short- and long-term beneficial effects in female patients with fibromyalgia", "Osteoarthritis is an important rheumatic condition characterized by the progressive destruction of cartilage . The pathophysiologic phenomena leading to the pathologic changes in the joint appear to result from biomechanical factors and activation of final common pathways of tissue damage influencing chondrocyte homeostasis and a functional program . Several cytokines and growth factors are reported to be responsible for inflammation and cartilage degradation . Among these , IL-1 and TNF alpha have been suggested as important in promoting cartilage inflammation and tissue destruction , while IGF I has a protective influence on cartilage structure . Chondrocytes and their metabolism have gained interest as targets of drug intervention ; the results of this study confirm that mud bath therapy is also able to influence chondrocyte activities . Our data suggest that mud bath therapy influences cytokines related to osteoarthrosis pathomechanism and maintenance , and encourage further investigations to evaluate possible synergism between pharmacological treatment and mud bath therapy", "Abstract . Fibromyalgia syndrome ( FMS ) is a very common rheumatological diagnosis . There are various treatment modalities . This study was planned to investigate the effects of balneotherapy in the treatment of FMS . A total of 42 primary fibromyalgia patients diagnosed according to American College of Rheumatology criteria were included in the study . Their ages ranged between 30 and 55 years . Patients were r and omly assigned to two groups . None of them had had a cardiovascular disease before . Group 1 ( n=22 ) received 20-min bathing , once a day and five times per week . Patients participated in the study for 3 weeks ( total of 15 sessions ) . Group 2 ( n=20 ) was accepted as the control group . Patients were evaluated by the number of tender points , Visual Analogue Scale for pain , Beck 's Depression Index for depression , and Fibromyalgia Impact Question naire for functional capacity . Measurements were assessed initially , after the therapy , and at the end of the 6th month . In group 1 , there were statistically significant differences in numbers of tender points , Visual Analogue scores , Beck 's Depression Index , and Fibromyalgia Impact Question naire scores after the therapy program ( P number of tender points ( P Visual Analogue scores , and Fibromyalgia Impact Question naire ( P Beck 's Depression Index scores compared to the control group ( P>0.05 ) . Patients with FMS mostly complain about pain , anxiety , and the difficulty in daily living activities . This study shows that balneotherapy is effective and may be an alternative method in treating fibromyalgia patients" ]

[ "We develop novel mixed effects models to examine the role of health traits on the status of peoples ' close friendship nominations in the Framingham Heart Study . The health traits considered are both mutable ( body mass index ( BMI ) , smoking , blood pressure , body proportion , muscularity , and depression ) and , for comparison , basically immutable ( height , birth order , personality type , only child , and h and edness ) ; and the traits have varying degrees of observability . We test the hypotheses that existing ties ( i.e. close friendship nominations ) are more likely to dissolve between people with dissimilar ( mutable and observable ) health traits whereas new ties are more likely to form between those with similar ( mutable and observable ) traits while controlling for persons ' age , gender , geographic separation , and education . The mixed effects models contain r and om effects for both the nominator ( ego ) and nominated ( alter ) persons in a tie to account for the fact that people were involved in multiple relationships and contributed observations at multiple exams . Results for BMI support the hypotheses that people of similar BMI are less likely to dissolve existing ties and more likely to form ties , while smoker to non-smoker ties were the least likely to dissolve and smoker to smoker ties were the most likely to form . We also vali date d previously known findings regarding homophily on age and gender , and found evidence that homophily also depends upon geographic separation . Copyright © 2011 John Wiley & Sons ,", "Human population s are both highly cooperative and highly organized . Human interactions are not r and om but rather are structured in social networks . Importantly , ties in these networks often are dynamic , changing in response to the behavior of one 's social partners . This dynamic structure permits an important form of conditional action that has been explored theoretically but has received little empirical attention : People can respond to the cooperation and defection of those around them by making or breaking network links . Here , we present experimental evidence of the power of using strategic link formation and dissolution , and the network modification it entails , to stabilize cooperation in sizable groups . Our experiments explore large-scale cooperation , where subjects ’ cooperative actions are equally beneficial to all those with whom they interact . Consistent with previous research , we find that cooperation decays over time when social networks are shuffled r and omly every round or are fixed across all rounds . We also find that , when networks are dynamic but are up date d only infrequently , cooperation again fails . However , when subjects can up date their network connections frequently , we see a qualitatively different outcome : Cooperation is maintained at a high level through network rewiring . Subjects preferentially break links with defectors and form new links with cooperators , creating an incentive to cooperate and leading to substantial changes in network structure . Our experiments confirm the predictions of a set of evolutionary game theoretic models and demonstrate the important role that dynamic social networks can play in supporting large-scale human cooperation", "Theoretical models suggest that social networks influence the evolution of cooperation , but to date there have been few experimental studies . Observational data suggest that a wide variety of behaviors may spread in human social networks , but subjects in such studies can choose to befriend people with similar behaviors , posing difficulty for causal inference . Here , we exploit a seminal set of laboratory experiments that originally showed that voluntary costly punishment can help sustain cooperation . In these experiments , subjects were r and omly assigned to a sequence of different groups to play a series of single-shot public goods games with strangers ; this feature allowed us to draw networks of interactions to explore how cooperative and uncooperative behaviors spread from person to person to person . We show that , in both an ordinary public goods game and in a public goods game with punishment , focal individuals are influenced by fellow group members ’ contribution behavior in future interactions with other individuals who were not a party to the initial interaction . Furthermore , this influence persists for multiple periods and spreads up to three degrees of separation ( from person to person to person to person ) . The results suggest that each additional contribution a subject makes to the public good in the first period is tripled over the course of the experiment by other subjects who are directly or indirectly influenced to contribute more as a consequence . These results show experimentally that cooperative behavior cascades in human social networks ", "Exponential r and om graph modeling ( ERGM ) is used here to test hypotheses derived from human behavioral ecology about the adaptive nature of human food sharing . Respondents in all ( n = 317 ) households in the fishing and sea-hunting village of Lamalera , Indonesia , were asked to name those households to whom they had more frequently given ( and from whom they had more frequently received ) food during the preceding sea-hunting season . The responses were used to construct a social network of between-household food-sharing relationships in the village . The results show that kinship , proximity , and reciprocal sharing all strongly increase the probability of giving food to a household . The effects of kinship and distance are relatively independent of each other , although reciprocity is more common among residentially and genealogically close households . The results show support for reciprocal altruism as a motivation for food sharing , while kinship and distance appear to be important partner-choice criteria", "Information exchanges , debates , and negotiations through community social networks are essential to ensure the sustainability of the development process initiated in participatory research . The authors analyze the structural properties and robustness of a discussion network about mercury issues in a community in the Brazilian Amazon involved in a participatory research aim ed at reducing exposure to the pollutant . Most of the villagers are connected in a large network and are separated from other individuals by few intermediaries . The structure of the discussion network displays resilience to the r and om elimination of villagers but shows vulnerability to the removal of one villager who has been a long-term collaborator of the project . Although the network exhibits a structure likely to favor an efficient flow of information , results show that specific actions should be taken to stimulate the emergence of a pool of opinion leaders and increase the redundancy of discussion channels", "The health benefits of delaying the introduction of complementary foods to infants ' diets are widely known . Many studies have shown that mothers with the support of close social network members are more compliant with medical recommendations for infant feeding . In our study , we examine the effects of a broader spectrum of network members ( 40 people ) on mothers ' infant feeding decisions . The survey was conducted in Oaxaca , Mexico as part of a follow-up to a nationwide Mexican Social Security Institute survey of infant health . Sixty mothers were interviewed from a stratified r and om sample of the original respondents . Multivariate tests were used to compare the efficacy of network-level variables for predicting the introduction of 36 foods into infants ' diets , when compared with respondent-level variables . The study yields four findings . First , network-level variables were better predictors of the timing of food introduction than socio-demographic variables . Second , mothers with more indigenous networks delayed the introduction of some grains ( oatmeal , cereal , noodle soup , rice ) and processed pork products ( sausage and ham ) to the infant 's diet longer than mothers with less indigenous networks . Third , mothers who had stronger ties to their networks delayed the introduction of rice and processed pork products ( sausage and ham ) to the infant 's diet longer than mothers who had weaker ties to their networks . Fourth , mothers who heeded the advice of distant network members introduced some grains ( rice and cereal ) earlier than mothers who did not heed the advice of distant network members", "Costly signaling has been proposed as a possible mechanism to explain food sharing in foraging population s. This sharing-as-signaling hypothesis predicts an association between sharing and status . Using exponential r and om graph modeling ( ERGM ) , this prediction is tested on a social network of between-household food-sharing relationships in the fishing and sea-hunting village of Lamalera , Indonesia . Previous analyses ( Nolin 2010 ) have shown that most sharing in Lamalera is consistent with reciprocal altruism . The question addressed here is whether any additional variation may be explained as sharing-as-signaling by high-status households . The results show that high-status households both give and receive more than other households , a pattern more consistent with reciprocal altruism than costly signaling . However , once the propensity to reciprocate and household productivity are controlled , households of men holding leadership positions show greater odds of unreciprocated giving when compared to households of non-leaders . This pattern of excessive giving by leaders is consistent with the sharing-as-signaling hypothesis . Wealthy households show the opposite pattern , giving less and receiving more than other households . These households may reciprocate in a currency other than food or their wealth may attract favor-seeking behavior from others . Overall , status covariates explain little variation in the sharing network as a whole , and much of the sharing observed by high-status households is best explained by the same factors that explain sharing by other households . This pattern suggests that multiple mechanisms may operate simultaneously to promote sharing in Lamalera and that signaling may motivate some sharing by some individuals even within sharing regimes primarily maintained by other mechanisms", "Objectives : Consuming contaminated food is a well-documented individual-level risk factor for diarrheal disease . The sharing of food also influences the distribution of diarrheal disease risk through a community and region . Underst and ing this social process at a population level is therefore an important dimension of risk not captured by st and ard individual-level analyses . We examined social networks related to food-sharing in rural villages at 2 scales : within a village , examining whether connections within these networks clustered or were uniformly spread ; and among villages , looking at whether food-sharing networks differed according to the village 's remoteness from a population center . Methods : We surveyed 2129 individuals aged 13 years and older in 2003–2004 , within a representative ( block-r and omized ) sample of 21 rural villages in Esmeraldas province , northern coastal Ecuador . We calculated degree ( number of social contacts ) for a social network defined by sharing food . Results : Networks of households sharing food differ according to remoteness from a metropolitan center . On average , residents living in “ far villages ” had 2 more social contacts than those in “ close villages , ” and 12 more years of residence in their village . Estimates of transmissibility ( a measure of outbreak potential ) based on network structure varied as much as 2-fold across these villages . Conclusions : Food-sharing practice s link particular households in rural villages and have implication s for the spread of food-borne pathogens . The food-sharing networks in remote rural villages are heterogeneous and clustered , consistent with contemporary theories about disease transmitters . Network-based measures may offer tools for predicting patterns of disease outbreaks , as well as guidance for interventions", "Human behaviour is thought to spread through face-to-face social networks , but it is difficult to identify social influence effects in observational studies , and it is unknown whether online social networks operate in the same way–. Here we report results from a r and omized controlled trial of political mobilization messages delivered to 61 million Facebook users during the 2010 US congressional elections . The results show that the messages directly influenced political self-expression , information seeking and real-world voting behaviour of millions of people . Furthermore , the messages not only influenced the users who received them but also the users ’ friends , and friends of friends . The effect of social transmission on real-world voting was greater than the direct effect of the messages themselves , and nearly all the transmission occurred between ‘ close friends ’ who were more likely to have a face-to-face relationship . These results suggest that strong ties are instrumental for spreading both online and real-world behaviour in human social networks" ]

[ "Background We have previously reported that 6 months of oral treatment with clodronate reduced the migration of the NexGen total knee prosthesis during the first postoperative year , as measured by radiostereometry ( RSA ) . We now report the 4-year results . Methods This was a double-blind r and omized study , using RSA with maximal total point motion ( MTPM ) . Results With analysis according to the “ intention to treat ” principle , the only remaining difference between the groups at 4 years was reduced rotation around the transverse axis ( a secondary variable ) in the clodronate group . However , 3 patients ( all clodronate ) did not take any tablet after surgery . If they are excluded , there was an almost statistically significant difference between the groups at 4 years regarding MTPM from baseline , with the clodronate group showing 25 % less migration . From 1 to 4 years , there was no difference in migration rate by MTPM , but there was a continuous increase in rotation around the transverse axis in the controls , which differed from the clodronate group . There were no cases of aseptic loosening . 2 patients had migration of more than 1.3 mm from baseline to 4 years ; neither of them had taken clodronate . The others had migration of less than 0.9 mm . Interpretation Because migration was clearly reduced by clodronate during the first postoperative year , and there was still a difference at 4 years when analyzed per protocol , it appears likely that this treatment can diminish the risk of loosening . The difference in the number of outliers also points in this direction , and may be more relevant than mean migration values", "BACKGROUND High-flexion total knee arthroplasty was introduced to meet the dem and s of daily activity requiring increased knee flexion . However , concerns have been raised regarding the fixation of high-flexion total knee arthroplasty components and increased rates of loosening have been reported . To date , migration , and thus fixation , of high-flexion total knee arthroplasty components has not been analyzed and the preferential bearing type ( mobile or fixed ) is unknown . METHODS Of eighty-six consecutive eligible patients , seventy-four patients ( seventy-eight knees ) scheduled for total knee arthroplasty were r and omized to one of four Legacy Posterior Stabilized ( LPS ) total knee prosthesis design s : ( 1 ) LPS-Flex mobile , ( 2 ) LPS-Flex fixed , ( 3 ) LPS mobile , and ( 4 ) LPS fixed . The primary outcome was component migration measured with use of Roentgen stereophotogrammetric analysis , and secondary outcomes were postoperative knee flexion and extension and Knee Society Score . Patients were evaluated postoperatively at six , twelve , twenty-six , and fifty-two weeks and annually thereafter . At the five-year follow-up , eight patients had died and two patients were lost to follow-up . Seventy-seven tibial and forty-two femoral components were suitable for migration measurements . RESULTS The overall five-year migration of the seventy-seven tibial components was not significantly different among the four total knee prosthesis design s ( compared with the LPS fixed design , the range of overall mean differences for the other three design s was 0.02 to 0.25 mm ) and migration was comparable at the two and five-year follow-up . Migration stabilized in all but three components ( two LPS-Flex mobile and one LPS fixed ) ; one of these components has already been revised and was aseptically loose . The overall five-year migration of the forty-two femoral components was comparable among the four design s ( compared with the LPS fixed design , the range of overall mean differences for the other three design s was 0.01 to 0.18 mm ) and was similar at two and five years postoperatively . One femoral component ( LPS-Flex mobile ) migrated excessively . In patients who had a mean postoperative flexion of ≥ 125 ° or a maximum flexion of ≥ 135 ° during the one to five-year follow-up period , migration of high-flexion components was comparable with that of conventional components and indicative of appropriate fixation . Postoperative flexion , extension , Knee Society Score , and Knee Society Score function were comparable during the five-year follow-up period and at the two and five-year follow-up . CONCLUSIONS The LPS-Flex total knee prosthesis with either a mobile or a fixed bearing had migration comparable that of with its conventional counterpart and is expected to have similar ( excellent ) long-term survival in these patients . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence", "Sixty-two knees ( 60 patients ) were r and omized to four noncemented groups . In Groups 1 , 3 , and 4 , the bone cuts were made with a cooled saw blade . In Group 1 , 15 patients were operated on with the porous coated Osteonic 7000 tibial component . In Group 2 , 15 patients were operated on with the same tibial component as in Group 1 but with the use of a st and ard saw blade . In Group 3 , 16 patients were operated on with the hydroxyapatite-coated Osteonic tibial component , and in Group 4 , 16 patients were operated on with the hydroxyapatite Duracon tibial component . All patients were followed up clinical ly and with roentgenstereometric analysis . There were no differences among the groups regarding clinical outcome . One knee was revised ( Group 2 ) after 1 year because of loosening of the tibial component . The maximum migration at 1 year was 1.7 mm in Group 1 , 1.9 mm in Group 2 , 1.3 mm in Group 3 , and 1 mm in Group 4 . At the 2-year followup , the migrations were 1.8 mm , 1.5 mm , 1.4 mm , and 1 mm in Groups 1 , 2 , 3 , and 4 , respectively . The inducible displacement that occurred at 1 year was 0.6 mm in Group 1 , 0.5 mm in Group 2 , 0.4 mm in Group 3 , and 0.4 mm in Group 4 . The hydroxyapatite coating had a strong positive effect on the tibial component fixation . No prosthesis in the hydroxyapatite groups showed continuous migration", "OBJECTIVES The objective of this study was to compare the early migration of the cruciate retaining and posterior stabilising versions of the recently introduced Triathlon ™ total knee system , with a view to predicting long term fixation performance . METHODS Sixty patients were prospect ively r and omised to receive either Triathlon ™ posterior stabilised cemented knee prosthesis or Triathlon ™ cruciate retaining cemented knee prosthesis . Tibial component migration was measured by radiostereometric analysis postoperatively and at three months , one year and two years . Clinical outcome was measured by the American Knee Society Score and Knee Osteoarthritis and Injury Outcome Score . RESULTS There were no differences in rotation around the three coordinal axes or in the maximum total point motion ( MTPM ) during the two year follow-up . The posterior stabilised prosthesis had more posterior-anterior translation at three months and one year and more caudal-cranial translation at one year and two years . There were no differences in functional outcome between the groups . CONCLUSION The tibial tray of the Triathlon ™ cemented knee prosthesis showed similar early stability . LEVEL OF EVIDENCE Level I. ARTICLE SUMMARY Article focus : This was a prospect i ve r and omised trial aim ing to compare the single radius posterior stabilised ( PS ) Triathlon ™ total knee arthroplasty ( TKA ) to the cruciate retaining Triathlon ™ TKA system with regard to fixation . Strengths and limitations of this study : Strength of this study was that it is a r and omised prospect i ve trial using an objective measuring tool . The sample size of 25 - 30 patients was reportedly sufficient for the screening of implants using RSA [ 1 ] . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00436982", "Abstract Objective : Migration of the tibial component in total knee arthroplasty ( TKA ) is subject of many studies using roentgen stereophotogrammetric analysis ( RSA ) . In previous studies of cemented and uncemented tibial components , high migration values were found . Improvements in cementing technique , prosthetic design and pre-coating techniques reduced these values as shown in more recent studies . Material and subjects : A total of 35 patients were initially included in the study and operated on between 12/1999 and 10/2000 . All patients received a NexGen ® TKA cemented into the proximal tibia using Palamed ® G bone cement . The implants and the tibial metaphysis were marked with st and ard tantalum markers . Radiostereometric analysis was performed post-operatively and after 3 , 6 and 12 months using a st and ard digital radiostereometric analysis . Functional parameters were assessed using the Knee Society Score ( KSS ) clinical rating system . Results : There were no complications and failures within the first year . After 1 year radiostereometric measurements of the translational parameters along and the rotational parameters around the x- , y- and z-axis revealed : X-Trans –0.19 mm , Y-Trans + 0.02 mm , Z-Trans + 0.08 mm , X-Rot + 0.26 ° , Y-Rot –0.35 ° , Z-Rot + 0.09 ° . The maximum total point motion was + 0.96 mm and the mean maximum subsidence was –0.23 mm . Except for anterior-posterior , medio-lateral stability and extension leg all endpoints of the KSS clinical rating system showed a significant improvement . Conclusions : After 12 months , the use of Palamed ® G bone cement in total knee arthroplasty was demonstrated to be safe . Both the clinical and radiostereometric results were good and comparable to the results reported in other RSA studies in cemented total knee arthroplasty", "This single-blinded r and omised controlled trial investigated whether one design of mobile-bearing ( MB ) total knee replacement ( TKR ) has any advantage over a fixed-bearing ( FB ) design on long-term fixation as measured by radiostereometry . The amount of wear underneath the mobile bearing was also evaluated . A series of 42 knees was r and omised to MB or FB tibial components with appropriate polyethylene inserts and followed for between ten and 12 years , or until the death of the patient . The polyethylene in the MB group was superior in that it was gamma-irradiated in inert gas and was calcium-stearate free ; the polyethylene in the FB group was gamma-irradiated in air and contained calcium stearate . In theory this should be advantageous to the wear rate of the MB group . At final follow-up the overall mean migration was 0.75 mm ( SD 0.76 ) in the MB group and 0.66 mm ( SD 0.4 ) in the FB group , with the FB group demonstrating more posterior tilt and the MB group more internal rotation . In the FB group there was one revision for aseptic loosening , but none in the MB group . There were no significant differences in clinical or radiological scores . For the MB group , the mean linear wear rate on the under-surface was 0.026 mm/year ( SD 0.014 ) . This was significantly smaller than the wear rate of 0.11 mm/year ( SD 0.06 ) in the MB between femur and polyethylene ( p wear underneath the mobile bearing was small and is unlikely to be clinical ly relevant", "Background The question whether the tibial component of a total knee arthroplasty should be fixed to bone with or without bone cement has not yet been definitely answered . We studied movements between the tibial component and bone by radiostereometry ( RSA ) in total knee replacement ( TKR ) for 3 different types of fixation : cemented fixation ( C-F ) , uncemented porous fixation ( UC-F ) and uncemented porous hydroxyapatite fixation ( UCHA-F ) . Patients 116 patients with osteoarthrosis , who had 146 TKRs , were included in 2 r and omized series . The first series included 86 unilateral TKRs stratified into 1 of the 3 types of fixation . The second series included 30 patients who had simultaneous bilateral TKR surgery , and who were stratified into 3 subgroups of pairwise comparisons of the 3 types of fixation . Results After 5 years 2 knees had been revised , neither of which were due to loosening . 1 UCHA-F knee in the unilateral series showed a large and continuous migration and a poor clinical result , and is a pending failure . The C-F knees rotated and migrated less than UC-F and UCHA-F knees over 5 years . UCHA-F migrated less than UC-F after 1 year . Interpretation Cementing of the tibial component offers more stable bone-implant contact for 5 years compared to uncemented fixation . When using uncemented components , however , there is evidence that augmenting a porous surface with hydroxyapatite may mean less motion between implant and bone after the initial postoperative year", "Background and purpose After joint replacement , a repair process starts at the interface between bone and cement . If this process is disturbed , the prosthesis may never become rigidly fixed to the bone , leading to migration— and with time , loosening . Cox-2 inhibitors are widely used as postoperative analgesics , and have adverse effects on bone healing . This could tamper prosthesis fixation . We investigated whether celecoxib , a selective Cox-2 inhibitor , increases prosthesis migration in total knee replacement ( TKR ) . Methods 50 patients were r and omized to either placebo or celecoxib treatment , 200 mg twice daily , for 3 weeks after TKR ( NexGen ; Zimmer ) . Maximum total point motion ( MTPM ) of the tibial component was measured after 2 years using radiostereometric analysis ( RSA ) . In addition , range of motion , pain , and , subjective outcome were evaluated . Results No differences in prosthesis migration , pain scores , range of motion , and subjective outcome were found after 2 years . Confidence intervals were narrow . Interpretation It is unlikely that Celecoxib increases the risk of loosening , and it may be used safely in conjunction with TKR", "Background and purpose In contrast to early migration , the long-term migration of hydroxyapatite- ( HA- ) coated tibial components in TKA has been scantily reported . This r and omized controlled trial investigated the long-term migration measured by radiostereometric analysis ( RSA ) of HA-coated , uncoated , and cemented tibial components in TKA . Patients and methods 68 knees were r and omized to HA-coated ( n = 24 ) , uncoated ( n = 20 ) , and cemented ( n = 24 ) components . All knees were prospect ively followed for 11–16 years , or until death or revision . RSA was used to evaluate migration at yearly intervals . Clinical and radiographic evaluation was according to the Knee Society system . A generalized linear mixed model ( GLMM , adjusted for age , sex , diagnosis , revisions , and BMI ) was used to take into account the repeated-measurement design . Results The present study involved 742 RSA analyses . The mean migration at 10 years was 1.66 mm for HA , 2.25 mm for uncoated and 0.79 mm for the cemented group ( p of migration by HA as compared to uncoated components was most pronounced for subsidence and external rotation . 3 tibial components were revised for aseptic loosening ( 2 uncoated and 1 cemented ) , 3 for septic loosening ( 2 uncoated and 1 cemented ) , and 1 for instability ( HA-coated ) . 2 of these cases were revised for secondary loosening after a period of stability : 1 case of osteolysis and 1 case of late infection . There were no statistically significant differences between the fixation groups regarding clinical or radiographic scores . Interpretation HA reduces migration of uncemented tibial components . This beneficial effect lasts for more than 10 years . Cemented components showed the lowest migration . Longitudinal follow-up of TKA with RSA allows early detection of secondary loosening", "Background Postoperative migration of a joint prosthesis is related to the risk of late loosening . We have previously reported that oral treatment with clodronate reduced migration of the cemented NexGen total knee prosthesis during the first postoperative year , as measured by radiostereometry ( RSA ) . Oral bisphosphonate treatment is sometimes unpleasant , and local treatment will enable higher local concentrations . We now report the results of local peroperative treatment with another bisphosphonate , ib and ronate , with the same prosthesis . Methods This is a double-blind , r and omized study of 50 patients using RSA with maximal total point motion ( MTPM ) as primary effect variable . 1 mg ib and ronate ( 1 mL ) or 1 mL saline was applied to the tibial bone surface 1 min before cementation . RSA examination was done on the first postoperative day , and at 6 , 12 , and 24 months . Results One ib and ronate-treated patient died of unrelated causes , and 1 control patient refused to come for follow-up , leaving 24 patients in each group for analysis . There were no cases of aseptic loosening . By repeated measures ANOVA , migration ( MTPM ) was reduced by local application of ib and ronate ( p = 0.006 ) . The effect was most pronounced at 6 months , with a reduction from 0.45 to 0.32 mm ( 95 % CI for reduction : 0.04–0.21 mm ) . At 12 months , the migration from the postoperative examination was reduced from 0.47 to 0.36 mm ( 95 % CI for reduction : 0.02–0.20 mm ) . At 24 months , the reduction was from 0.47 to 0.40 mm ( 95 % CI : -0.01–0.16 mm ) . Interpretation This is the first study to show improvement of prosthesis fixation by local pharmacological treatment in humans . The treatment appears to be safe , cheap , and easy to perform . However , the improvement in postoperative stability was not greater than with systemic clodronate treatment", "We compared Boneloc bone cement with conventional cement ( Palacos ) in fixating the tibial component during 2 - 5 years in 19 patients with gonarthrosis undergoing total knee arthroplasty in a prospect i ve r and omized study . Boneloc displayed significantly larger migration , subsidence and lift-off than Palacos . The difference was identifiable already within 3 months postoperatively , but became significant at 12 months . In the Boneloc group , all components showed subsidence of the posterior part and lift-off of the anterior part of the tibial component , whereas in the Palacos group , the locations of subsidence and lift-off were evenly distributed about the edge of the implant . At 5 years , both Boneloc knees so far investigated were clinical failures with high migration rates . We conclude that , even in total knee arthroplasty , there is a substantial risk that Boneloc leads to inferior clinical results , but later than in hip replacements", "Fifty-three consecutive patients ( 57 knees ; mean age , 69 years ) entered a prospect i ve r and omized study to compare the fixation of hydroxyapatite (HA)-coated ( 29 knees ) with cemented ( 28 knees ) tibial components in the Tricon II total knee arthroplasty . The quality of the fixation during 5 years postoperatively was evaluated with radiostereometric analysis ( RSA ) . Three HA-coated implants were revised : 2 owing to infection , and 1 owing to early delamination of the coating and clinical loosening . Eight patients ( 9 knees ) died , 1 patient sustained a stroke , and 1 patient refused investigations after 1 year . In the 40 patients ( 19 HA-coated , 21 cemented ) remaining at 5 years , the magnitude of the micromotion between the HA-coated and cemented groups did not differ . The HA-coated implants displayed most of the migration within the initial 3 months then stabilized , whereas the cemented implants showed an initially lower , but over time continuously increasing migration . Between 1 and 2 years , 4 of 24 HA-coated and 10 of 23 cemented implants migrated > 0.2 mm and were categorized unstable , which has been shown to have a prognostic value as regards future aseptic loosening . Progressive radiolucent lines developed in 2 cemented knees , which both were categorized unstable . If HA-coated implants can sustain the forces that threaten the fixation in the early period after implantation , a strong and enduring fixation may be obtained", "AIMS The purpose of the present study was to examine the long-term fixation of a cemented fixed-bearing polished titanium tibial baseplate ( Genesis ll ) . PATIENTS AND METHODS Patients enrolled in a previous two-year prospect i ve trial ( n = 35 ) were recalled at ten years . Available patients ( n = 15 ) underwent radiostereometric analysis ( RSA ) imaging in a supine position using a conventional RSA protocol . Migration of the tibial component in all planes was compared between initial and ten-year follow-up . Outcome scores including the Knee Society Score , Western Ontario and McMaster Universities Arthritis Index , 12-item Short Form Health Survey , Forgotten Joint Score , and University of California , Los Angeles Activity Score were recorded . RESULTS At ten years , the mean migration of the tibial component was less than 0.1 mm and 0.1 ° in all planes relative to the post-operative RSA exam . Maximum total point movement increased with time ( p = 0.002 ) from 0.23 mm ( sd 0.18 ) at six weeks to 0.42 mm ( sd 0.20 ) at ten years . CONCLUSION The low level of tibial baseplate migration found in the present study correlates to the low rate of revision for this implant as reported in individual studies and in joint replacement registries . TAKE HOME MESSAGE Overall , the implant was found to be well fixed at ten years , supporting its continued clinical use and the predictive power of RSA for determining long-term fixation of implants . Cite this article : Bone Joint J 2016;98-B:616 - 21", "We studied the effect of a layer of cement placed under the tibial component of Freeman-Samuelson total knee prostheses with a metal back and an 80 mm intramedullary stem , using roentgen stereophotogrammetry to measure the migration of the tibial component during one year in 13 uncemented and 16 cemented knees . The addition of cement produced a significant reduction in migration at one year , from a mean of 1.5 mm to one of 0.5 mm ( p less than 0.01 ) , including a significant reduction in pure subsidence . One year postoperatively the clinical results were similar between the groups , but , at three years , one uncemented knee had required revision", "A prospect i ve nation-wide study of knee arthroplasty has been under way in Sweden since October 1975 . By the end of 1983 , 4505 arthroplasties for osteoarthritis and 3495 for rheumatoid arthritis had been recorded and review ed one , three and six years after the operation . Using actuarial methods , the probability of the prosthesis remaining in situ after six years was calculated . In osteoarthritis this probability ranged from 65 % for hinged prostheses to 90 % for medial compartment prostheses . Two- and three-compartment prostheses produced intermediate results with 87 % survival . In rheumatoid arthritis the probability varied from 72 % for medial compartment prostheses to 90 % for two- and three-compartment prostheses . The main reason for failure was loosening of the components , the second most common was infection . The probability of revision for infection by six years was 2 % in osteoarthritis and 3 % in rheumatoid arthritis . Most revisions were to a three-compartment prosthesis . Knee fusion at primary revision was required in 2 % of the cases at six years", "Tibial migration in 33 cementless total knee replacements , which were performed with a cooled saw blade vs. a conventional blade , was studied in a r and omized prospect i ve study using roentgen stereophotogrammetric analysis ( radiostereometry ) . All cases were clinical ly successful after 2 years and inducible displacement was smaller in the group operated with the cooled saw blade . This group also had a tendency towards less continuous migration", "The fixation of tibial components r and omized to insertion with or without cement in twenty-six knees was examined for inducible displacement at six weeks and one year postoperatively with use of roentgen stereophotogrammetric analysis . Furthermore , migration was studied during the first two postoperative years . Inducible displacement was found in all knees at both the six-week and the one-year follow-up examination , but no differences were detected with respect to the type of fixation ( p > 0.05 ) . All tibial components migrated for as long as one year postoperatively , after which most stabilized . No difference was found between the groups with respect to migration during the first two years postoperatively ( p > 0.05 ) , with the exception of subsidence of the component , which was found to be 0.0 ± 0.1 millimeter ( mean and st and ard error of the mean ) for the components inserted with cement and 0.5 ± 0.1 millimeter for the components inserted without cement ( p . Migration after one year was the same for both groups . We found a relationship between inducible displacement at six weeks and at one year as well as one between inducible displacement and migration at one year . To our knowledge , the present study is the first in which the micromotion of an interference-fit prosthesis was found to be similar to that of a device inserted with cement . The results of the present study emphasize the importance of the initial prosthetic fixation", "We studied CMW-1 bone cement with gentamicin in the laboratory and in a r and omized clinical study . Palacos bone cement containing gentamicin was used as the control . In the pre clinical evaluation , the CMW cement had slightly less mechanical strength . In the clinical study , 51 patients ( 51 knees ) operated on with total knee arthroplasty were studied for 2 years . We used radiostereometric analysis to measure migration of the tibial components , r and omized to fixation with either of the two types of cement . The extent and pattern of migration were similar in both groups , and we found no differences in the number , size and extent of radiolucent lines or clinical outcome . No complications occurred . Our findings suggest a need for more studies of CMW-1 bone cement containing gentamicin in a larger cohort of patients", "Mobile bearings were introduced to improve wear and knee kinematics . By uncoupling the forces generated at the articulation from the implant-bone interface this would , theoretically , also improve the fixation of the implant to bone . We did this study to evaluate whether mobile bearings improve the fixation of the tibial component to bone . Fifty-two consecutive knees in 47 patients ( average age , 72 years ; range , 62 - 84 years ) with primary osteoarthrosis were r and omized into two groups to receive a cemented total knee arthroplasty with either a fixed-bearing or mobile-bearing tibial component . The quality of fixation was analyzed with radiostereometric analysis for up to 2 years . Mobile bearings did not improve fixation . Both magnitudes and directions of component rotations were similar , and the number of implants with continuous migration was almost identical . Both implant types had a combination of subsidence and lift-off , but where the mobile bearing implants displayed more of subsidence , the fixed bearing knees showed more lift-off . It might be that the somewhat stiffer cobalt-chromium baseplate or the different joint conformity used in the mobile-bearing knees counteracts any potential effects of the mobile bearing . Level of Evidence : Therapeutic Level I. See the Guidelines for Authors for a complete description of levels of evidence", "Twenty-six women and three men ( 34 knees ) with osteoarthrosis were operated with the Miller-Galante I ( Zimmer , Warsaw , IN ) knee prosthesis . The patients were r and omized to either cemented or uncemented fixation of the tibial component . All patients received a TiVaAl alloy tibial plate with four pegs and titanium fiber-mesh undersurface . In the uncemented knees four screws were added . The fixation of the tibial component was determined by roentgen stereophotogrammetric analysis during the first 2 postoperative years . Rotations of the entire tibial component were recorded , as well as proximal or distal translation of various parts of the prosthetic edge corresponding to subsidence and lift-off . The uncemented components displayed almost all rotation and translation during the first 6 weeks , whereas the cemented ones displayed a more gradually increasing migration during the 2 years . Tibial component rotation about the sagittal axis was significantly increased in the uncemented knees throughout the investigation period . This corresponded to increased subsidence medially or laterally in the uncemented knees , whereas lift-off was equal in the two groups . Thin ( 8.5 mm ) uncemented tibial components displayed more subsidence than the thicker ones at the medial or lateral edge 3 months after surgery", "BACKGROUND A concern that arises with any change in technique is whether it affects the long-term implant stability . The objective of this study was to evaluate the early migration , measured by radiostereometric analysis ( RSA ) , and the functional outcome of the Triathlon ™ cemented knee prosthesis , operated on with or without a tourniquet . During the last decades RSA has emerged as a way to assess prosthetic fixation and long time prognosis . The method has been used extensively in both hip and knee arthroplasty . METHOD This was a single centre prospect i ve study including 60 patients r and omized into two groups operated on either with or without tourniquet . RSA investigation was done within 2 - 3 days postoperatively after full weight bearing , and then at 3 months , 1 year and 2 years postoperatively . RESULTS There were no differences between the groups regarding the translation along or rotation around the three coordinal axes , or in maximum total point motion ( MTPM ) . At 2 years the mean MTPM ( SD ) was 0.71 mm ( 0.64 ) for the tourniquet-group and 0.53 mm ( 0.21 ) for the non-tourniquet-group . CONCLUSIONS The tibial tray of the Triathlon ™ cemented knee prosthesis showed similar early stability whether operated on with or without tourniquet . LEVEL OF EVIDENCE Level I. ARTICLE SUMMARY Article focus : A safety study for total knee replacement operated on with or without perioperative tourniquet regarding the prosthetic fixation . Strengths and limitations : Strength of this study is that it is a r and omized prospect i ve trial using an objective measuring tool . The sample size of 25 - 30 patients is reportedly sufficient for the screening of implants using RSA ( 1 - 3 ) . TRIAL REGISTRATION Clinical trials NCT01604382 , Ethics Committee approval D-nr : 144/20085", "Forty uncemented total knee arthroplasties ( 36 patients ) were r and omly allocated to a Miller-Galante II prosthesis with or without hydroxyapatite/tricalcium phosphate ( HA/TCP ) coating on the titanium fiber mesh on the undersurface of the tibial component . The patients were followed for 2 years with repeated radiostereometric examinations . After 2 years , the HA/TCP tibial components displayed smaller anterior-posterior tilt and less subsidence . The mean value of maximal total point motion was small : 0.5 mm in both groups . At 24 months , there were more radiolucent lines under the tibial tray and around the stem in the uncoated group , but the clinical results did not differ . HA/TCP coating on the undersurface of the tibial component improved the stability and seemed to improve the quality of the interface between the tibial component and the bone", "We conducted a prospect i ve , r and omized study of 45 patients to evaluate 3 different uncemented tibial component design s in total knee arthroplasty . The stability of the components was assessed by radiostereometry ( RSA ) , both as migration during 2 years and as inducible displacement at 2 years . The PCA resurfacing , the Tricon stem and the Tricon-M prosthesis groups showed a similar level of migration at 2 years , about 1.4 mm . In response to externally applied rotatory forces , the Tricon groups rotated more than the PCA group , interpreted as a consequence of the more conforming articular surface in the Tricon design . The series was divided into one group of continuously migrating prostheses with a poor prognosis ( unstable , one third ) and another group of prostheses in which migration stopped after 1 year ( stable , two thirds ) . With this classification , no differences between the prostheses design groups were revealed . However , the unstable group showed a larger inducible displacement by provocation , an association hitherto not established", "VersaBond is a newly developed bone cement . To investigate its clinical performance , VersaBond was compared to Palacos R in a prospect i ve r and omized study in total knee replacement . Fifty-nine patients ( 61 knees ) undergoing total knee replacement were r and omized to either VersaBond or Palacos R bone cement and followed for 24 months using radiostereometric analysis ( RSA ) . Up to 2 years there were no significant differences in clinical performance between the two cements . The mean/median values for implant migration were very similar for the two bone cements , as were the dispersion , and distribution of outliers . Also the proportion \" stable \" and \" continuously migrating \" implants was similar between the two cements . The result of this study indicates that VersaBond bone cement will perform at least equally as well as Palacos R in total knee replacement as regards as aseptic loosening", "We aim ed to determine whether not using a tourniquet in cemented TKA would affect migration of the tibial component measured by radiosterometric analysis ( RSA ) . Seventy patients were r and omized into a tourniquet group and a non-tourniquet group and using model-based RSA , the migration of the tibial component was analyzed . Primary and secondary outcome measures were maximum total point motion ( MTPM ) and translations and rotations . Follow-up period was 2 years . The tibial component was well fixated in both groups and no significant difference in migration between the two groups was detected ( P=0.632 ) . Mean MTPM ( SD ) was 0.47 mm ( 0.16 ) in the tourniquet group and 0.45 mm ( 0.21 ) in the non-tourniquet group . Absence of tourniquet indicates that stable fixation of the tibial component can be achieved in cemented TKA" ]

[ "OBJECTIVE Given the perceived technical dem and s of laparoscopic appendectomy and the expected postoperative morbidity in patients with a well-defined abscess , initial percutaneous drainage has become an attractive option in this patient population . This strategy allows for a laparoscopic appendectomy to be performed in an elective manner at the convenience of the surgeon . However , the medical burden on the patient and on the quality of patient outcomes has not been described in the literature . Therefore , we audited our experience with initial percutaneous drainage followed by laparoscopic interval appendectomy to evaluate the need for a prospect i ve trial . METHODS After institutional review board approval , a retrospective chart review was performed on all children who presented with perforated appendicitis and a well-defined abscess and were treated by initial percutaneous aspiration/drainage followed by interval appendectomy between January 2000 and September 2006 . Continuous variables are listed with st and ard deviation . RESULTS There were 52 patients with a mean age of 9.0 + /- 3.9 years and weight of 34.4 + /- 18.8 kg . The mean duration of symptoms at presentation was 8.4 + /- 7.6 days . Percutaneous aspiration only was performed in 2 patients . The mean volume of fluid on initial aspiration/drain placement was 76.3 + /- 81.1 mL. The mean time to appendectomy was 61.9 + /- 25.2 days . The laparoscopic approach was used in 49 patients ( 94.2 % ) , of which one was converted to an open operation . The mean length of hospitalization after interval appendectomy was 1.4 + /- 1.4 days . A recurrent abscess developed in 17.3 % of the patients . Six patients ( 11.5 % ) required another drainage procedure . The mean total charge to the patients was $ 40,414.02 . There were 4 significant drain complications ( ileal perforation , colon perforation , bladder perforation , and buttock/thigh necrotizing abscess ) . The child with the ileal perforation after drain placement is the only patient who failed initial nonoperative therapy . CONCLUSIONS The use of initial percutaneous aspiration/drainage of periappendiceal abscess followed by interval appendectomy is an effective approach . However , this management poses complication risks and uses considerable re sources . Therefore , this strategy should be compared with early operation in a prospect i ve trial", "AIM This prospect i ve study was done to evaluate the feasibility and safety of immediate appendicectomy in the presence of appendicular mass . METHODS A prospect i ve , nonr and omized study was conducted over 46 consecutive patients ( mean age : 24 ± 8.76 years ) presenting with an appendicular mass over a 4-year period . They were subjected for immediate appendicectomy within 24 h of admission . RESULTS The appendix was identified and removed in all 46 patients at operation . Peri-appendiceal abscesses were present in 25 % ( 11 of 46 ) . There was difficulty with adhesolysis and localization of the appendix in 10%(4 ) of patients . Superficial wound infection had occurred in 8(17 % ) while deep wound infection had occurred in 9%(4 ) patients . The mean hospital stay was 3 ± 0.25 day . No major complications had occurred . CONCLUSIONS Early surgical intervention in patients with an appendicular mass is feasible , safe and avoids the consequences of the misdiagnosis and mistreatment of other surgical pathologies", "PURPOSE The aim of of this study was to evaluate prospect ively the long-term outcome of mesocolic and pelvic diverticular abscesses of the left colon . METHODS Between October 1986 and October 1997 , a total of 465 patients urgently admitted to our hospital with a suspected diagnosis of acute left-sided colonic diverticulitis had a CT scan . Of 76 patients ( 17 percent ) who had an associated mesocolic or pelvic abscess , 3 were lost to follow-up . The remaining 73 patients ( 45 with a mesocolic abscess and 28 with a pelvic abscess ) were followed for a median of 43 months . RESULTS of the 45 patients with a mesocolic abscess , 7 ( 15 percent ) required surgery during their first hospitalization versus 11 ( 39 percent ) of the 28 patients with a pelvic abscess ( P = 0.04 ) . At the end of follow-up , 22 ( 58 percent ) of the 38 patients with a mesocolic abscess who had successful conservative treatment during their first hospitalization did not need surgical treatment vs. 8 ( 47 percent ) of the 17 who had a pelvic abscess . Altogether , 51 percent of the patients with a mesocolic abscess had surgical treatment versus 71 percent of those with a pelvic abscess ( P = 0.09 ) . CONCLUSIONS Considering the poor outcome of pelvic abscess associated with acute left-sided colonic diverticulitis , percutaneous drainage followed by secondary colectomy seems justified . Mesocolic abscess by itself is not an absolute indication for colectomy", "PURPOSE Prospect i ve evaluation was undertaken of surgical findings , complications , morbidity , and hospital stay between initial nonsurgical management versus early surgical intervention of an appendicular mass . METHODS A prospect i ve , nonr and omized study was conducted of 82 consecutive patients ( mean age , 6.9 + /- 3.3 years ) presenting with an appendicular mass over a 5-year period . They were categorized as group 1 , 58.5 % ( 48 of 82 ) nonsurgically managed and an interval appendectomy performed at a mean period of 8.6 + /- 4.6 weeks and group 2 , 41.5 % ( 34 of 82 ) appendectomy at presentation . RESULTS An appendix was identified in all 82 patients in both groups at operation . In-group 1 , recurrent episodes of abdominal pain necessitated interval appendectomy in 39.6 % ( 19 of 48 ) patients at a mean 4.3 + /- 0.8 versus 11.5 + /- 3.7 weeks in 60.4 % ( 29 of 48 ) who underwent scheduled interval appendectomy . Periappendiceal abscesses present at interval appendectomy in group 1 was ( 38 of 48 ) 79.2 % versus 100 % ( 34 of 34 ) at appendectomy in group 2 . Adhesions at interval appendectomy in group 1 was 81.3 % ( 39 of 48 ) versus 100 % ( 34 of 34 ) at appendectomy in group 2 . In-group 1 , superficial wound infection was observed in 0 versus 4 wound infections in group 2 . Overall morbidity rate between group 1 and group 2 was statistically significant ( P Total mean hospital stay in group 1 was 13.2 + /- 1.5 versus 4.8 + /- 0.4 days in group 2 . Of the 48-interval appendectomy specimens , 37 of 48 ( 77 % ) appendices had a patent lumen , and 11 of 48 ( 23 % ) showed fibrosis and obliteration of appendicular lumen . There was no correlation ( r = 0.22 ) between the histopathologic findings and the interval between abscess treatment and interval appendectomy . CONCLUSIONS Early surgical intervention was beneficial over nonoperative management in this cohort of patients . Interval appendectomy is recommended after nonsurgical management of an appendicular mass", "BACKGROUND Surgical management of acute appendicitis with appendiceal abscess or phlegmon remains controversial . We studied the results of initial conservative treatment ( antibiotics and percutaneous drainage if necessary , with or without interval appendectomy ) compared with immediate surgery . METHODS We undertook an observational , retrospective cohort study of patients with a clinical and radiological diagnosis of acute appendicitis with an abscess or phlegmon , treated in our hospital between January 1997 and March 2009 . Patients younger than 14 , with severe sepsis or with diffuse peritonitis were excluded . A study group of 15 patients with acute appendicitis complicated with an abscess or phlegmon underwent conservative treatment . A control group was composed of the other patients , who all underwent urgent appendectomy , matched for age and later r and omized 1:1 . The infectious risk stratification was established with the National Nosocomial Infections Surveillance System ( NNIS ) index . Dependent variables were hospital stay and surgical site infection . Analysis was with SPSS , with p Interval appendectomy was performed in 7 study group patients . Surgical site infection episodes were more frequent in the control group ( 6 vs. 0 , p of high risk patients ( NNIS ≥ 2 ) was identified in the control group ( 80 vs. 28.7 % , p < 0.03 ) , mostly related with contaminated or dirty procedures in this group ( p < 0.001 ) . No significant difference between groups was found in hospital stay . CONCLUSION Initial conservative treatment should be considered the best therapeutic choice for acute appendicitis with abscess or phlegmon", "BACKGROUND : Ileocecal resection is the most commonly performed operation in patients with Crohn ’s disease . Anastomotic-associated complications , with their associated morbidity , are the most feared risks of surgery . OBJECTIVE : This study aim ed to assess the influence of a variety of putative risk factors in a homogenous group of patients undergoing first or subsequent surgery for Crohn ’s disease to quantify the cumulative risk for anastomotic-associated complications . DESIGN AND PATIENTS : All patients undergoing ileocecal or ileocolic resections for Crohn ’s disease from 2000 to 2010 were studied with the use of a prospect i ve data base . Demographics , operative details , possible risk factors , and anastomotic-associated complications were recorded . Patients having strictureplasties , multiple resections , or subtotal colonic resections were excluded from analysis . Statistical analysis was by univariate analysis ( Mann-Whitney U test ) and binary logistic regression . OUTCOMES : An anastomotic-associated complication was defined as a proven anastomotic leak , postoperative fistulation , or intra-abdominal abscess formation . RESULTS : Two hundred seven patients ( 109 female ) with a median age of 35 years ( range , 13 - 75 years ) were identified . One hundred seventy-three underwent primary anastomosis , 94 as an emergency procedure . Fifty-three had laparoscopic ( 5 converted ) procedures . Nineteen of 173 anastomotic complication events ( 11 % ) were recorded . Steroid usage ( OR 2.67 , 95 % CI 1.0 - 7.2 ) and the presence of preoperative abscess formation ( OR 3.4 , 95 % CI 1.2 - 9.8 ) were identified as independent predictors of anastomotic-associated complications . In the absence of both steroids and intra-abdominal abscess , the risk of anastomotic complications was 6 % , which increased to 14 % if either risk factor was present . When both risk factors were present , complication rates reached 40 % . CONCLUSION : Steroid usage and preoperative abscess were associated with higher rates of anastomotic complications following ileocolic resection for Cohn ’s disease . When both risk factors are present , it is best to avoid primary anastomosis", "Background The present study was design ed to compare the therapeutic effectiveness of percutaneous drainage with antibiotics versus antibiotics alone in the treatment of appendicitis complicated by periappendiceal abscess . Methods In a prospect i ve study , 50 patients with acute appendicitis complicated by periappendiceal abscess ≥ 3 cm in size were r and omly assigned to two groups . The first group received treatment with ultrasound guided-percutaneous drainage and i.v . antibiotics ( ampicillin , cefuroxime , and metronidazole ) , and the other group received antibiotics only . Patient ’s baseline characteristics , duration of hospital stay , and treatment outcome and complications were analyzed . Results Appendectomy was avoided in 16/25 patients in the drainage group and 2/25 patients in the non-drainage group during follow-up with RR of 0.39 ( 95 % CI = 0.22–0.62 ; p regarding patient demographics , abscess size , and pretreatment clinical symptoms . Hospital stay up to the subsidence of clinical and sonographic signs was significantly shorter ( p Percutaneous drainage with antibiotics is a safe and effective way of treating acute perforated appendicitis . The recurrence rate for these patients is relatively low , and very often interval appendectomy is not required . For patients with periappendiceal abscess ≥ 3 cm in diameter , antibiotic therapy alone is insufficient and the recurrence rate is high", "BACKGROUND Current therapy of patients with appendiceal abscess or phlegmon is in evolution . Controversial areas include initial conservative therapy , drainage of periappendiceal abscesses , and the role of interval appendectomy . OBJECTIVE To evaluate the safety and efficacy of conservative therapy and of interval laparoscopic appendectomy ( ILA ) . PATIENTS AND METHODS Patients with signs and symptoms of acute appendicitis and a palpable right lower quadrant mass were included . Abscess/phlegmon was documented with ultrasound or computerized tomography . After initial therapy with antibiotics , patients were discharged to home . ILA was performed 6 to 12 weeks later . RESULTS Twelve patients were included . Four patients had phlegmonous appendicitis and eight had an abscess , but only four had percutaneous drainage . All patients improved without surgical exploration and were subjected to ILA . ILA was successful in 11 of 12 patients ; a median hospital postoperative stay of 1 day was required , and no perioperative morbidity was encountered . All patients returned to routine activities within 2 weeks of surgery . CONCLUSIONS 1 ) Initial conservative management of patients with appendiceal abscess/phlegmon is prudent , safe , and effective . 2 ) Interval laparoscopic appendectomy can be performed safely and effectively", "BACKGROUND The management of an appendiceal mass remains controversial with 2 schools of thought ; early surgical intervention vs nonoperative management with or without interval appendectomy . The aim is to determine the role and safety of early laparoscopic appendectomy ( LA ) in children with acute appendicitis presenting with an appendiceal mass . METHODS This is a prospect i ve study of 88 consecutive pediatric patients who underwent attempted LA for suspected acute appendicitis at KK Women 's and Children 's Hospital , Singapore , between May and October 2003 . RESULTS A total of 88 patients with a mean age of 10 + /- 3 years ( range , 3 - 16 years ) underwent LA for an appendiceal mass ( n = 22 ) , simple appendicitis ( n = 36 ) , other complicated ( gangrenous or perforated ) appendicitis ( n = 23 ) , and a normal appendix ( n = 7 ) . There were 7 conversions to open appendicectomy , 3 of which occurred in patients with an appendiceal mass . There were no perioperative or postoperative mortalities . Morbidity occurred in only one patient who underwent LA for perforated appendicitis . He had prolonged sepsis that resolved after 2 weeks of intravenous antibiotics . None of the patients with an appendiceal mass developed complications . Patients who underwent early LA for an appendiceal mass had a statistically significant ( P operating time ( median , 103 minutes ; interquartile range , 90 - 151 minutes , vs median , 87 minutes ; interquartile range , 71 - 112 minutes ) , prolonged time to ambulation ( median , 2.0 days ; interquartile range , 2 - 2.5 days , vs median , 1.0 days ; interquartile , 1 - 2 days ) , increased time to resumption of diet ( median , 4 days ; interquartile , 3 - 5 days , vs median , 2 days ; interquartile , 2 - 3 days ) , and longer postoperative stay ( median , 6.0 days ; interquartile , 5.5 - 6.5 days , vs median , 4.0 days ; interquartile , 3 - 5.5 days ) compared with patients presenting with appendicitis without mass formation . However , there was no statistical difference in these parameters when LA for an appendiceal mass was compared with LA for other complicated appendicitis ( perforated and gangrenous ) . CONCLUSION Although early LA for an appendiceal mass is a technically dem and ing procedure , it can be performed safely in children with minimal morbidity and mortality . In an era where patients ' dem and for \" key-hole \" surgery is rising , early LA is a safe and viable option in the management of children with an appendiceal mass . It also offers the advantage of avoiding misdiagnoses and the need for a second hospitalization", "The st and ard treatment for an appendiceal mass is conservative therapy followed by appendectomy after 6 to 10 weeks . With the advent of antibiotics design ed to prevent the growth of anaerobes , early appendectomy can now be carried out without complication . The authors studied 56 patients with appendiceal mass formation , 26 ( group A ) treated conventionally and 30 ( group B ) treated by early appendectomy . In group B , the infection rate was 17 % , the mean operating time was 38.7 minutes , the mean hospital stay was 15 days and there was an early return to work . The corresponding parameters for group A were an infection rate of 8 % , a mean operating time of 35.2 minutes , a hospital stay of 19.1 days and a late return to work . Furthermore , 15 % of the patients in group A had a recurrent acute episode during the waiting period . Overall , early appendectomy appears to be a safe and cost-effective treatment for appendiceal mass formation", "INTRODUCTION Perforated appendicitis is a common condition in children , which , in a small number of patients , may be complicated by a well-formed abscess . Initial nonoperative management with percutaneous drainage/aspiration of the abscess followed by intravenous antibiotics usually allows for an uneventful interval appendectomy . Although this strategy has become well accepted , there are no published data comparing initial nonoperative management ( drainage/interval appendectomy ) to appendectomy upon presentation with an abscess . Therefore , we conducted a r and omized trial comparing these 2 management strategies . METHODS After internal review board approval ( # 06 11 - 164 ) , children who presented with a well-defined abdominal abscess by computed tomographic imaging were r and omized on admission to laparoscopic appendectomy or intravenous antibiotics with percutaneous drainage of the abscess ( when possible ) , followed by interval laparoscopic appendectomy approximately 10 weeks later . This was a pilot study with a sample size of 40 , which was based on our recent volume of patients presenting with appendicitis and abscess . RESULTS On presentation , there were no differences between the 2 groups regarding age , weight , body mass index , sex distribution , temperature , leukocyte count , number of abscesses , or greatest 2-dimensional area of abscess in the axial view . Regarding outcomes , there were no differences in length of total hospitalization , recurrent abscess rates , or overall charges . There was a trend toward a longer operating time in patients undergoing initial appendectomy ( 61 minutes versus 42 minutes mean , P = .06 ) . CONCLUSIONS Although initial laparoscopic appendectomy trends toward a requiring longer operative time , there seems to be no advantages between these strategies in terms of total hospitalization , recurrent abscess rate , or total charges", "BACKGROUND Appendiceal mass may be treated in several ways . However , no r and omized trial has been conducted to find the best option . OBJECTIVE To compare the three most commonly used methods for treating appendiceal mass . METHODS Over a three-year period , 60 consecutive patients with appendiceal mass were r and omly allocated to three groups : Group A -- initial conservative treatment followed by interval appendectomy six weeks later ; Group B -- appendectomy as soon as appendiceal mass resolved using conservative means ; Group C -- conservative treatment alone . Short-term outcome measures included operative time , operative difficulty , postoperative complications , length of hospital stay , and duration of time away from work . Long-term outcome measures were : number of hospital visits made , presence of severe incisional pain , scar appearance , and patients with recurrent appendicitis . RESULTS Baseline characteristics were comparable in the three groups . In patients in Group A , operative time was less , adhesions were encountered less frequently , the incision had to be extended less often and post-operative complications were fewer , as compared to Group B. Patients in Group C had the shortest hospital stay and duration of work-days lost ; only 2 of 20 patients in this group developed recurrent appendicitis during a follow-up period of 24 - 52 ( median 33.5 ) months . CONCLUSION Of the three treatment modalities compared , conservative treatment without subsequent appendectomy appears to be the best" ]

[ "ABSTRACT Objective “ The obesity epidemic ” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease ( NAFLD ) , for which effective treatments are in dem and . The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction . We aim ed to test the hypothesis that resveratrol alleviates NAFLD in a r and omised , clinical trial . Material s and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were r and omised 1:1 to placebo or resveratrol 1.5 g daily for 6 months . Twenty-six participants completed the trial and underwent repeated clinical investigation , blood work , MR spectroscopy ; and 19 participants agreed to a repeat liver biopsy . Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury ( primary outcome : alanine transaminase , p = 0.51 ) . Resveratrol-treated patients showed a 3.8 % decrease in liver lipid content ( p = 0.03 ) , with no difference between the two treatment arms ( p = 0.38 ) and no improvement of histological features . Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome , except for a transient decrease in systolic BP . Microarray analysis and qRT-PCR revealed no major changes in expression profile . Also , we report a serious adverse event in a patient who developed fever and bicytopenia . Conclusions In this placebo-controlled , high-dose and long-term study , resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD , though there may be a small ameliorating effect on liver function tests and liver fat accumulation ", "Resveratrol is a naturally occurring polyphenolic compound . Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus ( DM ) . We hypothesized , therefore , that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus ( T2DM ) . The present clinical study was therefore carried out to test the hypothesis . Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital , Ootacamund , India , in a prospect i ve , open-label , r and omized , controlled trial . Patients were r and omized into control and intervention groups . The control group received only oral hypoglycemic agents , whereas the intervention group received resveratrol ( 250 mg/d ) along with their oral hypoglycemic agents for a period of 3 months . Hemoglobin A(1c ) , lipid profile , urea nitrogen , creatinine , and protein were measured at the baseline and at the end of 3 months . The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c ) ( means ± SD , 9.99 ± 1.50 vs 9.65 ± 1.54 ; P ( mean ± SD , 139.71 ± 16.10 vs 127.92 ± 15.37 ; P ( mean ± SD , 4.70 ± 0.90 vs 4.33 ± 0.76 ; P ( mean ± SD , 75.6 ± 4.6 vs 72.3 ± 6.2 ; P No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed . Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes", "Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies . However , there are few interventional studies in human patients with atherosclerogenic diseases . The cardio-ankle vascular index ( CAVI ) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis . The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind , r and omized , placebo-controlled study , 50 patients with T2DM received supplement of a 100 mg resveratrol tablet ( total resveratrol : oligo-stilbene 27.97 mg/100 mg/day ) or placebo daily for 12 weeks . CAVI was assessed at baseline and the end of study . Body weight ( BW ) , blood pressure ( BP ) , glucose and lipid metabolic parameters , and diacron-reactive oxygen metabolites ( d-ROMs ; an oxidative stress marker ) were also measured . Resveratrol supplementation decreased systolic BP ( -5.5 ± 13.0 mmHg ) , d-ROMs ( -25.6 ± 41.8 U.CARR ) , and CAVI ( -0.4 ± 0.7 ) significantly ( P decreased BW ( -0.8 ± 2.1 kg , P = 0.083 ) and body mass index ( -0.5 ± 0.8 kg/m2 , P = 0.092 ) slightly compared to baseline , while there were no significant changes in the placebo group . Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group . Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion , 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM . Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes . However , a large-scale cohort study is required to vali date the present findings", "Purpose The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from r and omized human clinical trials is very limited . We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease ( CAD ) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease . Methods In a triple-blind , r and omized , placebo-controlled , one-year follow-up , 3-arm pilot clinical trial , 75 stable-CAD patients received 350 mg/day of placebo , resveratrol-containing grape extract ( grape phenolics plus 8 mg resveratrol ) or conventional grape extract lacking resveratrol during 6 months , and a double dose for the following 6 months . Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed . Moreover , the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells ( P BMC s ) was explored using microarrays and functional gene expression analysis . Results After 1 year , in contrast to the placebo and conventional grape extract groups , the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin ( 9.6 % , p = 0.01 ) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 ( PAI-1 ) ( −18.6 % , p = 0.05 ) . In addition , 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited , with 27 extracellular-space acting genes involved in inflammation , cell migration and T-cell interaction signals presenting downregulation ( p No adverse effects were detected in relation to the study products . Conclusions Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence -based st and ards , by increasing serum adiponectin , preventing PAI-1 increase and inhibiting atherothrombotic signals in P BMC", "The objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of st and ard antidiabetic treatment in patients with type 2 diabetes , in a r and omized placebo-controlled double-blinded parallel clinical trial . A total of 66 subjects with type 2 diabetes were enrolled in this study and r and omly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets . Body weight , blood pressure , fasting blood glucose , haemoglobin A1c , insulin , homeostatic assessment s for insulin resistance , triglycerides , total cholesterol , low density lipoprotein , high density lipoprotein , and markers of liver and kidney damage were measured at baseline and after 45 days of resveratrol or placebo supplementation . Resveratrol treatment significantly decreased systolic blood pressure , fasting blood glucose , haemoglobin A1c , insulin , and insulin resistance , while HDL was significantly increased , when compared to their baseline levels . On the other h and , the placebo group had slightly increased fasting glucose and LDL when compared to their baseline levels . Liver and kidney function markers were unchanged in the intervention group . Overall , this study showed that resveratrol supplementation exerted strong antidiabetic effects in patients with type 2 diabetes", "CONTEXT Metabolic syndrome ( MetS ) is associated with low- grade inflammation , which may harmfully affect bone . Resveratrol ( RSV ) possesses anti-inflammatory properties , and rodent studies suggest bone protective effects . OBJECTIVE This study sought to evaluate effects of RSV treatment on bone in men with MetS. SETTING AND DESIGN The study was conducted at Aarhus University Hospital as a r and omized , double-blinded , placebo-controlled trial assessing changes in bone turnover markers , bone mineral density ( BMD ) , and geometry . PARTICIPANTS The study population comprised 74 middle-aged obese men with MetS recruited from the general community , of which 66 completed all visits . Mean age of participants was 49.3 ± 6.3 years and mean body mass index was 33.7 ± 3.6 kg/m(2 ) . INTERVENTION Oral treatment with 1.000 mg RSV ( RSV(high ) ) , 150 mg RSV ( RSV(low ) ) , or placebo daily for 16 weeks . MAIN OUTCOME MEASURE Prespecified primary endpoint was change in bone alkaline phosphatase ( BAP ) . RESULTS BAP increased dose dependently with RSV ( R = 0.471 , P increase in BAP in the RSV(high ) group compared with placebo at all time-points ( week 4 , 16.4 ± 4.2 % , P ) also increased dose dependently with RSV ( R = 0.268 , P = .036 ) , with a significant increase of 2.6 ± 1.3 % in the RSV(high ) group compared with placebo ( P = .043 ) . In addition , changes in BAP and LS vBMD(trab ) were positively correlated ( R = 0.281 , P = .027 ) . No consistent changes were detected in bone density at the hip . CONCLUSIONS Our data suggest that high-dose RSV supplementation positively affects bone , primarily by stimulating formation or mineralization . Future studies of longer duration comprising population s at risk of osteoporosis are needed to confirm these results", "OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P between plasma levels of a metabolite of resveratrol ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes", "Non-alcoholic fatty liver disease ( NAFLD ) is usually associated with insulin resistance , central obesity , reduced glucose tolerance , type 2 diabetes mellitus and hypertriacylglycerolaemia . The beneficial effects of resveratrol on metabolic disorders have been shown previously . The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD . In this r and omised double-blinded placebo-controlled clinical trial , fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . resveratrol supplementation reduced alanine aminotransferase ( ALT ) and hepatic steatosis significantly more than placebo ( P0·05 ) . There were no significant changes in blood pressure , insulin resistance markers and TAG in either group ( P>0·05 ) . Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements , insulin resistance markers , lipid profile and blood pressure ; however , it reduced ALT and hepatic steatosis in patients with NAFLD", "BACKGROUND & AIMS Nonalcoholic fatty liver disease ( NAFLD ) , characterized by accumulation of hepatic triglycerides ( steatosis ) , is associated with abdominal obesity , insulin resistance , and inflammation . Although weight loss via calorie restriction reduces features of NAFLD , there is no pharmacologic therapy . Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism . We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD . METHODS Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane , Australia from 2011 through 2012 . They were r and omly assigned to groups given 3000 mg resveratrol ( n = 10 ) or placebo ( n = 10 ) daily for 8 weeks . Outcomes included insulin resistance ( assessed by the euglycemic-hyperinsulinemic clamp ) , hepatic steatosis , and abdominal fat distribution ( assessed by magnetic resonance spectroscopy and imaging ) . Plasma markers of inflammation , as well as metabolic , hepatic , and antioxidant function , were measured ; transcription of target genes was measured in peripheral blood mononuclear cells . Resveratrol pharmacokinetics and safety were assessed . RESULTS Eight-week administration of resveratrol did not reduce insulin resistance , steatosis , or abdominal fat distribution when compared with baseline . No change was observed in plasma lipids or antioxidant activity . Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group . Resveratrol did not significantly alter transcription of NQO1 , PTP1B , IL6 , or HO1 in peripheral blood mononuclear cells . Resveratrol was well-tolerated . CONCLUSIONS Eight weeks administration of resveratrol did not significantly improve any features of NAFLD , compared with placebo , but it increased hepatic stress , based on observed increases in levels of liver enzymes . Further studies are needed to determine whether agents that are purported to mimic calorie restriction , such as resveratrol , are safe and effective for complications of obesity . Clinical trials registration no : ACTRN12612001135808", "Background : We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation ( FMD ) in the brachial artery after resveratrol consumption in mildly hypertensive , overweight/obese adults . Resveratrol supplementation has also been shown to increase cerebral blood flow acutely , without affecting cognition . Objectives : To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance . Method : Twenty-eight obese but otherwise healthy adults ( BMI : 33.3 ± 0.6 kg/m2 ) were r and omized to take a single 75 mg capsule of trans-resveratrol ( Resvida ) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial . Blood pressure , arterial compliance , FMD , and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule . An additional capsule of the same supplement was then taken . FMD assessment was repeated 1 h later . Results : Chronic resveratrol supplementation for 6 weeks was well tolerated and result ed in a 23 % increase in FMD compared with placebo ( P = 0.021 , paired t-test ) . The extent of increase correlated negatively with baseline FMD ( r = −0.47 , P = 0.01 ) . A single dose of resveratrol ( 75 mg ) following chronic resveratrol supplementation result ed in a 35 % greater acute FMD response than the equivalent placebo supplementation . These FMD improvements remained significant after adjusting for baseline FMD . Blood pressure , arterial compliance , and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation . Conclusion : Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults" ]

[ "Objective : To determine whether falls can be prevented with minimally supervised exercise targeting potentially remediable fall risk factors , i.e. , poor balance , reduced leg muscle strength , and freezing of gait , in people with Parkinson disease . Methods : Two hundred thirty-one people with Parkinson disease were r and omized into exercise or usual-care control groups . Exercises were practice d for 40 to 60 minutes , 3 times weekly for 6 months . Primary outcomes were fall rates and proportion of fallers during the intervention period . Secondary outcomes were physical ( balance , mobility , freezing of gait , habitual physical activity ) , psychological ( fear of falling , affect ) , and quality -of-life measures . Results : There was no significant difference between groups in the rate of falls ( incidence rate ratio [ IRR ] = 0.73 , 95 % confidence interval [ CI ] 0.45–1.17 , p = 0.18 ) or proportion of fallers ( p = 0.45 ) . Preplanned subgroup analysis revealed a significant interaction for disease severity ( p falls in the exercise group compared with controls ( IRR = 0.31 , 95 % CI 0.15–0.62 , p Short Physical Performance Battery , sit-to-st and , fear of falling , affect , and quality of life , after adjusting for baseline performance . Conclusions : An exercise program targeting balance , leg strength , and freezing of gait did not reduce falls but improved physical and psychological health . Falls were reduced in people with milder disease but not in those with more severe Parkinson disease . Classification of evidence : This study provides Class III evidence that for patients with Parkinson disease , a minimally supervised exercise program does not reduce fall risk . This study lacked the precision to exclude a moderate reduction or modest increase in fall risk from exercise . Trial registration : Australian New Zeal and Clinical Trials Registry ( ACTRN12608000303347 )", "Purpose . To trial four-week 's physiotherapy targeting chair transfers for people with Parkinson 's disease ( PwPD ) and explore the feasibility of reliance on remote outcome measurement to preserve blinding . Scope . We recruited 47 PwPD and r and omised 24 to a focused home physiotherapy programme ( exercise , movement strategies , and cueing ) and 23 to a control group . We evaluated transfers ( plus mobility , balance , posture , and quality of life ) before and after treatment and at followup ( weeks 0 , 4 , 8 , and 12 ) from video produced by , and question naires distributed by , treating physiotherapists . Participants fed back via end-of- study question naires . Thirty-five participants ( 74 % ) completed the trial . Excluding dropouts , 20 % of question naire data and 9 % of video data were missing or unusable ; we had to evaluate balance in situ . We noted trends to improvement in transfers , mobility , and balance in the physiotherapy group not noted in the control group . Participant feedback was largely positive and assessor blinding was maintained in every case . Conclusions . Intense , focused physiotherapy at home appears acceptable and likely to bring positive change in those who can participate . Remote outcome measurement was successful ; question naire followup and further training in video production would reduce missing data . We advocate a fully powered trial , design ed to minimise dropouts and preserve assessor blinding , to evaluate this intervention", "Objectives : To determine whether 12-week home-based exergame step training can improve stepping performance , gait and complementary physical and neuropsychological measures associated with falls in Parkinson ’s disease . Design : A single-blinded r and omised controlled trial . Setting : Community ( experimental intervention ) , university laboratory ( outcome measures ) . Subjects : Sixty community-dwelling people with Parkinson ’s disease . Interventions : Home-based step training using videogame technology . Main measures : The primary outcomes were the choice stepping reaction time test and Functional Gait Assessment . Secondary outcomes included physical and neuropsychological measures associated with falls in Parkinson ’s disease , number of falls over six months and self-reported mobility and balance . Results : Post intervention , there were no differences between the intervention ( n = 28 ) and control ( n = 25 ) groups in the primary or secondary outcomes except for the Timed Up and Go test , where there was a significant difference in favour of the control group ( P = 0.02 ) . Intervention participants reported mobility improvement , whereas control participants reported mobility deterioration — between-group difference on an 11-point scale = 0.9 ( 95 % confidence interval : −1.8 to −0.1 , P = 0.03 ) . Interaction effects between intervention and disease severity on physical function measures were observed ( P = 0.01 to P = 0.08 ) with seemingly positive effects for the low-severity group and potentially negative effects for the high-severity group . Conclusion : Overall , home-based exergame step training was not effective in improving the outcomes assessed . However , the improved physical function in the lower disease severity intervention participants as well as the self-reported improved mobility in the intervention group suggest home-based exergame step training may have benefits for some people with Parkinson ’s disease", "BACKGROUND Poor locomotion and balance in Parkinson 's disease ( PD ) often diminishes independence . Accordingly , gait is considered one of the most relevant rehabilitation outcomes , and home-based balance exercises might be a viable mode of exercise delivery for individuals with PD . However , research on PD interventions rarely indicate best practice s to deliver exercises . Therefore , this study endeavoured to compare the efficacy of a home-based and therapist-supervised balance programme on gait parameters , dynamic balance , balance confidence and motivation in individuals diagnosed with PD . METHODS An experimental study design , including a cluster r and omized convenience sample , of 40 participants with idiopathic PD ( Hoehn and Yahr stage I-III ; age : 65.0±7.7years ) . Participants were divided into a therapist-supervised ( n=24 ) and home-based group ( n=16 ) . Groups received either eight weeks of balance training with an exercise therapist or a DVD . Outcome measures include the instrumented Timed-Up- and -Go , Functional Gait Analysis ( FGA ) , Activity-specific Balance confidence ( ABC ) scale and Intrinsic Motivation Inventory ( IMI ) . RESULTS Both groups improved in stride length ( p Similar FGA improved by 9 % and 16 % in the therapist-supervised and home-based group , respectively ( p improvements in ABC ( p=0.051 ) , stride velocity ( p=0.0006 ) and cadence ( p=0.046 ) over the intervention ; the latter two were also better compared to home-based ( p by an exercise therapist included somewhat more benefits after the intervention i.e. stride velocity and cadence in individuals with mild to moderate PD", "QUESTIONS For people with idiopathic Parkinson 's disease , does a 6-week , comprehensive , home exercise program reduce falls and disability and improve health-related quality of life ? Is the program cost-effective ? DESIGN R and omised , controlled trial with concealed allocation and assessor blinding . PARTICIPANTS One hundred and thirty-three community-dwelling adults with Parkinson 's disease . INTERVENTION The experimental group completed a 6-week home program comprising progressive resistance strength training , movement strategy training and falls education . The control group completed 6 weeks of non-specific life skills training . Participants in both groups received weekly therapist-guided sessions for 6 consecutive weeks and a weekly self-directed home program . OUTCOME MEASURES The primary outcome was the rate of falls , documented for the 12-month period immediately after therapy . Secondary outcomes were disability and health-related quality of life , assessed before and after intervention and at a 12-month follow-up . RESULTS A total of 2255 falls were reported by the 12-month follow-up . The proportion of fallers in the experimental and control groups was 61 and 72 % , respectively , which was not statistically significantly different ( RR=0.85 , 95 % CI 0.66 to 1.09 ) . There was no significant between-group difference in the rate of falls ( incidence rate ratio=1.58 , 95 % CI 0.73 to 3.43 ) . A survival analysis of participant time to first fall did not show a significant between-group difference ( log-rank test χ2=0.79 , p=0.37 ) . No significant between-group differences occurred for mobility , disability or quality of life . The mean cost of delivering the experimental intervention was AUD1596 . CONCLUSION A home program of strength and movement strategy training and falls education does not prevent falls when applied at the dose used in this study . Arguably , the dosage of therapy was insufficient . Future trials need to explore further therapy content , repetitions and duration , in order to optimise outcomes and cost-effectiveness . [ Morris ME , Taylor NF , Watts JJ , Evans A , Horne M , Kempster P , Danoudis M , McGinley J , Martin C , Menz HB ( 2017 ) A home program of strength training , movement strategy training and education did not prevent falls in people with Parkinson 's disease : a r and omised trial . Journal of Physiotherapy 63 : 94 - 100 ]", "Introduction Telerehabilitation enables patients to access remote rehabilitation services for patient-physiotherapist videoconferencing in their own homes . Home-based virtual reality ( VR ) balance training has been shown to reduce postural instability in patients with Parkinson 's disease ( PD ) . The primary aim was to compare improvements in postural stability after remotely supervised in-home VR balance training and in-clinic sensory integration balance training ( SIBT ) . Methods In this multicenter study , 76 PD patients ( modified Hoehn and Yahr stages 2.5–3 ) were r and omly assigned to receive either in-home VR telerehabilitation ( n = 38 ) or in-clinic SIBT ( n = 38 ) in 21 sessions of 50 minutes each , 3 days/week for 7 consecutive weeks . VR telerehabilitation consisted of grade d exergames using the Nintendo Wii Fit system ; SIBT included exercises to improve postural stability . Patients were evaluated before treatment , after treatment , and at 1-month follow-up . Results Analysis revealed significant between-group differences in improvement on the Berg Balance Scale for the VR telerehabilitation group ( p = 0.04 ) and significant Time × Group interactions in the Dynamic Gait Index ( p = 0.04 ) for the in-clinic group . Both groups showed differences in all outcome measures over time , except for fall frequency . Cost comparison yielded between-group differences in treatment and equipment costs . Conclusions VR is a feasible alternative to in-clinic SIBT for reducing postural instability in PD patients having a caregiver", "Objective : To investigate the feasibility and effectiveness of six weeks of home-based treadmill training in people with mild Parkinson ’s disease . Design : Pilot r and omized controlled trial of a six-week intervention followed by a further six weeks follow-up . Setting : Home-based treadmill training with outcome measures taken at a hospital clinic . Participants : Twenty cognitively intact participants with mild Parkinson ’s disease and gait disturbance . Two participants from the treadmill training group and one from the control group dropped out . Interventions : The treadmill training group undertook a semi-supervised home-based programme of treadmill walking for 20–40 minutes , four times a week for six weeks . The control group received usual care . Main outcome measures : The feasibility of the intervention was assessed by recording exercise adherence and acceptability , exercise intensity , fatigue , muscle soreness and adverse events . The primary outcome measure of efficacy was walking capacity ( 6-minute walk test distance ) . Results : Home-based treadmill training was feasible , acceptable and safe with participants completing 78 % ( SD 36 ) of the prescribed training sessions . The treadmill training group did not improve their walking capacity compared to the control group . The treadmill training group showed a greater improvement than the control group in fatigue at post test ( P = 0.04 ) and in quality of life at six weeks follow-up testing ( P = 0.02 ) . Conclusions : Semi-supervised home-based treadmill training is a feasible and safe form of exercise for cognitively intact people with mild Parkinson ’s disease . Further investigation regarding the effectiveness of home-based treadmill training is warranted", "Background The minimal detectable change ( MDC ) is the smallest amount of difference in individual scores that represents true change ( beyond r and om measurement error ) . The MDCs of the Timed “ Up & Go ” Test ( TUG ) and the Dynamic Gait Index ( DGI ) in people with Parkinson disease ( PD ) are largely unknown , limiting the interpretability of the change scores of both measures . Objective The purpose of this study was to estimate the MDCs of the TUG and the DGI in people with PD . Design This investigation was a prospect i ve cohort study . Methods Seventy-two participants were recruited from special clinics for movement disorders at a university hospital . Their mean age was 67.5 years , and 61 % were men . All participants completed the TUG and the DGI assessment s twice , about 14 days apart . The MDC was calculated from the st and ard error of measurement . The percentage MDC ( MDC% ) was calculated as the MDC divided by the mean of all scores for the sample . Furthermore , the intraclass correlation coefficient was used to examine the reproducibility between testing sessions ( test-retest reliability ) . Results The respective MDC and MDC% of the TUG were 3.5 seconds and 29.8 , and those of the DGI were 2.9 points and 13.3 . The test-retest reliability values for the TUG and the DGI were high ; the intraclass correlation coefficients were .80 and .84 , respectively . Limitations The study sample was a convenience sample , and the participants had mild to moderately severe PD . Conclusions The results showed that the TUG and the DGI have generally acceptable r and om measurement error and test-retest reliability . These findings should help clinicians and research ers determine whether a change in an individual patient with PD is a true change", "Objectives : To compare the effects of a physiotherapist-supervised exercise programme in an exercise unit and self-supervised home exercise programme on quality of life in patients with Parkinson ’s disease . Design : Assessor-blinded , quasi-r and omized trial ( alternate allocation ) . Setting : An outpatient exercise unit ; home setting s. Participants : Thirty patients with idiopathic Parkinson ’s disease , Hoehn & Yahr I — III , stable medication use . Interventions : Patients were included in the physiotherapist-supervised or home group . The exercise programme was performed for 10 weeks , three times/week either under the supervision of a physiotherapist or at home without supervision . Main outcome measures : Parkinson ’s Disease Quality of Life Question naire ( PDQLQ ) , Nottingham Health Profile ( NHP ) , Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , Beck Depression Inventory ( BDI ) . Results : Patients in the supervised physiotherapy group improved more than the home exercise group in Parkinson ’s Disease Quality of Life Question naire ( total score , Parkinson ’s symptoms , emotional function ) , Nottingham Health Profile total , Unified Parkinson ’s Disease Rating Scale ( all domains ) and Beck Depression Inventory scores . Conclusions : The exercise programme under physiotherapist supervision was found to be more effective at improving activities of daily living , motor , mental , emotional functions and general health quality in patients with Parkinson ’s disease compared with a self-supervised home programme", "Background People with Parkinson ’s ( PwP ) experience frequent and recurrent falls . As these falls may have devastating consequences , there is an urgent need to identify cost-effective interventions with the potential to reduce falls in PwP. The purpose of this economic evaluation is to compare the costs and cost-effectiveness of a targeted exercise programme versus usual care for PwP who were at risk of falling . Methods One hundred and thirty participants were recruited through specialist clinics , primary care and Parkinson ’s support groups and r and omised to either an exercise intervention or usual care . Health and social care utilisation and health-related quality of life ( EQ-5D ) were assessed over the 20 weeks of the study ( ten-week intervention period and ten-week follow up period ) , and these data were complete for 93 participants . Incremental cost per quality adjusted life year ( QALY ) was estimated . The uncertainty around costs and QALYs was represented using cost-effectiveness acceptability curves . Results The mean cost of the intervention was £ 76 per participant . Although in direction of favour of exercise intervention , there was no statistically significant differences between groups in total healthcare ( −£128 , 95 % CI : -734 to 478 ) , combined health and social care costs ( £ -35 , 95 % CI : -817 to 746 ) or QALYs ( 0.03 , 95 % CI : -0.02 to 0.03 ) at 20 weeks . Nevertheless , exploration of the uncertainty surrounding these estimates suggests there is more than 80 % probability that the exercise intervention is a cost-effective strategy relative to usual care . Conclusion Whilst we found no difference between groups in total healthcare , total social care cost and QALYs , analyses indicate that there is high probability that the exercise intervention is cost-effective compared with usual care . These results require confirmation by larger trial-based economic evaluations and over the longer term", "This r and omized controlled trial with blinded assessment aim ed to determine the effect of a 6-month minimally supervised exercise program on fall risk factors in people with Parkinson 's disease ( PD ) . Forty-eight participants with PD who had fallen or were at risk of falling were r and omized into exercise or control groups . The exercise group attended a monthly exercise class and exercised at home three times weekly . The intervention targeted leg muscle strength , balance , and freezing . The primary outcome measure was a PD falls risk score . The exercise group had no major adverse events and showed a greater improvement than the control group in the falls risk score , which was not statistically significant ( between group mean difference = -7 % , 95 % CI -20 to 5 , P = 0.26 ) . There were statistically significant improvements in the exercise group compared with the control group for two secondary outcomes : Freezing of Gait Question naire ( P = 0.03 ) and timed sit-to-st and ( P = 0.03 ) . There were statistically nonsignificant trends toward greater improvements in the exercise group for measures of muscle strength , walking , and fear of falling , but not for the measures of st and ing balance . Further investigation of the impact of exercise on falls in people with PD is warranted", "There is research evidence that exercise and motor training are beneficial for people with Parkinson 's disease ( PD ) , and clinicians seek to implement optimal programs . This paper summarizes important factors about the nature and reporting of r and omized controlled trials of exercise and /or motor training for people with PD which are likely to influence the translation of research into clinical practice . Search es identified 53 relevant trials with 90 interventions conducted for an average duration of 8.3 ( SD 4.2 ) weeks . Most interventions were fully supervised ( 74 % ) and conducted at a facility ( 79 % ) . Retention rates were high with 69 % of interventions retaining ≥85 % of their participants ; however adherence was infrequently reported , and 72 % of trials did not report adverse events . Overall , the labor-intensive nature of most interventions tested in these trials and the sparse reporting of adherence and adverse events are likely to pose difficulties for therapists attempting to balance benefits and costs when selecting protocol s that translate to sustainable clinical practice for people with PD", "Background . Highly challenging exercises have been suggested to induce neuroplasticity in individuals with Parkinson ’s disease ( PD ) ; however , its effect on clinical outcomes remains largely unknown . Objective . To evaluate the short-term effects of the HiBalance program , a highly challenging balance-training regimen that incorporates both dual-tasking and PD-specific balance components , compared with usual care in elderly with mild to moderate PD . Methods . Participants with PD ( n = 100 ) were r and omized , either to the 10-week HiBalance program ( n = 51 ) or to the control group ( n = 49 ) . Participants were evaluated before and after the intervention . The main outcomes were balance performance ( Mini-BESTest ) , gait velocity ( during normal and dual-task gait ) , and concerns about falling ( Falls Efficacy Scale – International ) . Performance of a cognitive task while walking , physical activity level ( average steps per day ) , and activities of daily living were secondary outcomes . Results . A total of 91 participants completed the study . After the intervention , the between group comparison showed significantly improved balance and gait performance in the training group . Moreover , although no significant between group difference was observed regarding gait performance during dual-tasking ; the participants in the training group improved their performance of the cognitive task while walking , as compared with the control group . Regarding physical activity levels and activities of daily living , in comparison to the control group , favorable results were found for the training group . No group differences were found for concerns about falling . Conclusions . The HiBalance program significantly benefited balance and gait abilities when compared with usual care and showed promising transfer effects to everyday living . Long-term follow-up assessment s will further explore these effects", "Objective : To investigate the effect of home exercises on the motor performance of patients with Parkinson 's disease . Design : A prospect i ve blinded study with allocation of patients into their groups by alternate weeks . Setting : A University Hospital neurology and physiotherapy department . Subjects : Recruited from a movement disorders outpatient clinic of Cerrahpasa School of Medicine diagnosed with Parkinson 's disease , classified as Hoehn and Yahr Grade s I , II and III . Interventions : Patients who fulfilled the inclusion criteria were recruited to the study . Each patient was evaluated at the end of first and second month after the baseline evaluation . Patients were divided into two groups . Those in the first and third week were put in the exercise group and second and fourth week in the control group . Patients in the exercise group ( n=15 ) were given a schedule of exercises to undertake at home ; the others ( n=15 ) did not receive this instruction . Measures : Ten- and 20-m walking test , first pace length , pace number in 10 m , walking around a chair , Nine Hole Peg Board ( NHPB ) test . Results : Following the home exercise programme , patients in the exercise group showed improvement in walking 10 and 20 m , time elapsed to complete walking around a chair and length of the first pace length , and in the motor performance of both h and s ( p home-based rehabilitation programme for patients with Parkinson 's disease helped to improve motor performance compared to patients who did not take advantage of a regular , professionally design ed exercise programme", "BACKGROUND AND PURPOSE The Timed \" Up & Go \" Test ( TUG ) is used to measure the ability of patients to perform sequential locomotor tasks that incorporate walking and turning . This study investigated the retest reliability , interrater reliability , and sensitivity of scores obtained with the TUG in detecting changes in mobility in subjects with idiopathic Parkinson disease ( PD ) . SUBJECTS The performance of 12 people with PD was compared with that of 12 age-matched comparison subjects without PD . METHODS The subjects with PD completed 5 trials of the TUG after withdrawal of levodopa for 12 hours ( \" off \" phase of the medication cycle ) as well as an additional 5 trials 1 hour after levodopa was administered ( \" on \" phase of the medication cycle ) . They were scored on the Modified Webster Scale at both sessions . The comparison subjects also performed 5 TUG trials . All trials were videotaped and timed by 2 experienced raters . The videotape was later rated by 3 experienced clinicians and 3 inexperienced clinicians . RESULTS For the subjects with PD , within-session performance was highly consistent , with correlations ( r ) ranging from.80 to.98 for the \" off \" phase and from.73 to.99 for the \" on \" phase . The performance of the comparison subjects across the 5 trials was also highly consistent ( r=.90-.97 ) . Comparisons showed differences between trials 1 and 2 on the TUG for both groups . Removal of data for trial 1 ( the practice trial ) further enhanced retest reliability . There was close agreement in TUG scores among raters despite different levels of experience ( intraclass correlation coefficient [3,1]=.87-.99 ) . Mean TUG scores were different between the \" on \" and \" off \" phases of the levodopa cycle and between subjects with PD and comparison subjects during the \" on \" phase . CONCLUSION AND DISCUSSION Retest reliability and interrater reliability of the TUG measurements were high , and the measurements reflected changes in performance according to levodopa use . The TUG can also be used to detect differences in performance between people with PD and elderly people without PD", "Background Recently , a new tool for assessing dynamic balance impairments has been presented : the 14-item Mini-BESTest . Objective The aim of this study was to compare the psychometric performance of the Mini-BESTest and the Berg Balance Scale ( BBS ) . Design A prospect i ve , single-group , observational design was used in the study . Methods Ninety-three participants ( mean age=66.2 years , SD=13.2 ; 53 women , 40 men ) with balance deficits were recruited . Interrater ( 3 raters ) and test-retest ( 1–3 days ) reliability were calculated using intraclass correlation coefficients ( ICCs ) . Responsiveness and minimal important change were assessed ( after 10 sessions of physical therapy ) using both distribution-based and anchor-based methods ( external criterion : the 15-point Global Rating of Change [ GRC ] scale ) . Results At baseline , neither floor effects nor ceiling effects were found in either the Mini-BESTest or the BBS . After treatment , the maximum score was found in 12 participants ( 12.9 % ) with BBS and in 2 participants ( 2.1 % ) with Mini-BESTest . Test-retest reliability for total scores was significantly higher for the Mini-BESTest ( ICC=.96 ) than for the BBS ( ICC=.92 ) , whereas interrater reliability was similar ( ICC=.98 versus .97 , respectively ) . The st and ard error of measurement ( SEM ) was 1.26 and the minimum detectable change at the 95 % confidence level ( MDC95 ) was 3.5 points for Mini-BESTest , whereas the SEM was 2.18 and the MDC95 was 6.2 points for the BBS . In receiver operating characteristic curves , the area under the curve was 0.92 for the Mini-BESTest and 0.91 for the BBS . The best minimal important change ( MIC ) was 4 points for the Mini-BESTest and 7 points for the BBS . After treatment , 38 participants evaluated with the Mini-BESTest and only 23 participants evaluated with the BBS ( out of the 40 participants who had a GRC score of ≥3.5 ) showed a score change equal to or greater than the MIC values . Limitations The consecutive sampling method drawn from a single rehabilitation facility and the intrinsic weakness of the GRC for calculating MIC values were limitations of the study . Conclusions The 2 scales behave similarly , but the Mini-BESTest appears to have a lower ceiling effect , slightly higher reliability levels , and greater accuracy in classifying individual patients who show significant improvement in balance function", "OBJECTIVE To assess the criterion-related validity of the Berg Balance Scale ( BBS ) in subjects with Parkinson 's disease ( PD ) . DESIGN Prospect i ve , correlational analysis between the BBS and accepted measures of PD motor and functional impairment . SETTING The federally funded PD research center , an interdisciplinary center of excellence for people with PD within a Veterans Affairs medical center . PARTICIPANTS Thirty-eight men ( average + /- st and ard deviation , 71.1+/-10.5 y ) with confirmed PD . Their initial diagnosis had been made on average 5.8+/-3.6 years earlier . All could st and or walk unassisted and had mild to moderate disability . Patients who could not ambulate without assistive devices were excluded . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Correlational analyses between the BBS and the Unified Parkinson 's Disease Rating Scale ( UPDRS ) motor scale , Modified Hoehn and Yahr Staging ( Hoehn and Yahr ) Scale , and the Modified Schwab and Engl and Capacity for Daily Living Scale ( S&E ADL Scale ) . RESULTS BBS score showed significant correlations with indicators of motor functioning , stage of disease , and daily living capacity . BBS score was inversely associated with the UPDRS motor score ( -.58 , P Hoehn and Yahr Scale staging ( -.45 , P S&E ADL Scale rating ( .55 , P UPDRS scores ( indicating greater motoric or functional impairment ) . CONCLUSIONS Results support the criterion-related validity of the BBS . Its utility in other balance conditions of older adults has been established . Rehabilitation interventions have been shown to improve the balance deficits associated with PD . Early referral and periodic re assessment is vital to achieving and maintaining improvements . Our research results agree with other published research in suggesting that the BBS may be used as a screening tool and ongoing assessment tool for patients with PD", "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 .", "Objective : To evaluate the effectiveness of a personalised home programme of exercises and strategies for repeat fallers with Parkinson ’s disease ( PD ) . Method : Patients with a confirmed diagnosis of idiopathic PD , independently mobile , living at home in the community , experiencing more than one fall in the previous 12 months and with intact gross cognitive function were invited to participate in this r and omised controlled trial . Usual care was compared with a personalised 6 week , home based exercise and strategy programme . The primary outcomes were rates of falling at 8 weeks and 6 months . Whether participants had repeat fallen , nearly fallen or experienced injurious falls were also examined . Functional Reach , the Berg Balance Test , PD Self- assessment Scale and the Euro Quol were rated by a blinded assessor . Results : Participants were r and omised to the exercise ( n = 70 ) and control ( n = 72 ) groups . There was a consistent trend towards lower fall rates in the exercise group at both 8 weeks and 6 months and lower rates of injurious falls needing medical attention at 6 months . Lower rates of repeat near falling were evident for the exercise group at 8 weeks ( p = 0.004 ) and 6 months ( p = 0.007 ) . There was a positive effect of exercises at 6 months on Functional Reach ( p = 0.009 ) and quality of life ( p = 0.033 ) . No significant differences were found on other secondary outcomes measures . Conclusion : There was a trend towards a reduction in fall events and injurious falls with a positive effect of exercises on near falls and quality of life", "Background . Falls are common and disabling in people with Parkinson ’s disease ( PD ) . There is a need to quantify the effects of movement rehabilitation on falls in PD . Objective . To evaluate 2 physical therapy interventions in reducing falls in PD . Methods . We r and omized 210 people with PD to 3 groups : progressive resistance strength training coupled with falls prevention education , movement strategy training combined with falls prevention education , and life-skills information ( control ) . All received 8 weeks of out-patient therapy once per week and a structured home program . The primary end point was the falls rate , recorded prospect ively over a 12 month period , starting from the completion of the intervention . Secondary outcomes were walking speed , disability , and quality of life . Results . A total of 1547 falls were reported for the trial . The falls rate was higher in the control group compared with the groups that received strength training or strategy training . There were 193 falls for the progressive resistance strength training group , 441 for the movement strategy group and 913 for the control group . The strength training group had 84.9 % fewer falls than controls ( incidence rate ratio [ IRR ] = 0.151 , 95 % CI 0.071 - 0.322 , P training group had 61.5 % fewer falls than controls ( IRR = 0.385 , 95 % CI 0.184 - 0.808 , P = .012 ) . Disability scores improved in the intervention groups following therapy while deteriorating in the control group . Conclusions . Rehabilitation combining falls prevention education with strength training or movement strategy training reduces the rate of falls in people with mild to moderately severe PD and is feasible", "Objectives : Gait and mobility problems are difficult to treat in people with Parkinson ’s disease . The Rehabilitation in Parkinson ’s Disease : Strategies for Cueing ( RESCUE ) trial investigated the effects of a home physiotherapy programme based on rhythmical cueing on gait and gait-related activity . Methods : A single-blind r and omised crossover trial was set up , including 153 patients with Parkinson ’s disease aged between 41 and 80 years and in Hoehn and Yahr stage II – IV . Subjects allocated to early intervention ( n = 76 ) received a 3-week home cueing programme using a prototype cueing device , followed by 3 weeks without training . Patients allocated to late intervention ( n = 77 ) underwent the same intervention and control period in reverse order . After the initial 6 weeks , both groups had a 6-week follow-up without training . Posture and gait scores ( PG scores ) measured at 3 , 6 and 12 weeks by blinded testers were the primary outcome measure . Secondary outcomes included specific measures on gait , freezing and balance , functional activities , quality of life and carer strain . Results : Small but significant improvements were found after intervention of 4.2 % on the PG scores ( p = 0.005 ) . Severity of freezing was reduced by 5.5 % in freezers only ( p = 0.007 ) . Gait speed ( p = 0.005 ) , step length ( p and timed balance tests ( p = 0.003 ) improved in the full cohort . Other than a greater confidence to carry out functional activities ( Falls Efficacy Scale , p = 0.04 ) , no carry-over effects were observed in functional and quality of life domains . Effects of intervention had reduced considerably at 6-week follow-up . Conclusions : Cueing training in the home has specific effects on gait , freezing and balance . The decline in effectiveness of intervention effects underscores the need for permanent cueing devices and follow-up treatment . Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in Parkinson ’s disease", "Background and Purpose : Comparative studies of exercise interventions for people with Parkinson disease ( PD ) rarely considered how one should deliver the intervention . The objective of this study was to compare the success of exercise when administered by ( 1 ) home exercise program , ( 2 ) individualized physical therapy , or ( 3 ) a group class . We examined if common comorbidities associated with PD impacted success of each intervention . Methods : Fifty-eight people ( age = 63.9 ± 8 years ) with PD participated . People were r and omized into ( 1 ) home exercise program , ( 2 ) individual physical therapy , or ( 3 ) group class intervention . All arms were st and ardized and based on the Agility Boot Camp exercise program for PD , 3 times per week for 4 weeks . The primary outcome measure was the 7-item Physical Performance Test . Other measures of balance , gait , mobility , quality of life , balance confidence , depressions , apathy , self-efficacy and UPDRS-Motor , and activity of daily living scores were included . Results : Only the individual group significantly improved in the Physical Performance Test . The individual exercise showed the most improvements in functional and balance measures , whereas the group class showed the most improvements in gait . The home exercise program improved the least across all outcomes . Several factors effected success , particularly for the home group . Discussion and Conclusions : An unsupervised , home exercise program is the least effective way to deliver exercise to people with PD , and individual and group exercises have differing benefits . Furthermore , people with PD who also have other comorbidities did better in a program directly supervised by a physical therapist . Video Abstract available for additional insights from the authors ( see Video , Supplemental Digital Content 1 , http://links.lww.com/JNPT/A112 )", "Objectives To compare the effectiveness of an exercise programme with usual care in people with Parkinson 's disease ( PD ) who have a history of falls . Design Pragmatic r and omised controlled trial . Setting Recruitment was from three primary and four secondary care organisations , and PD support groups in South West Engl and . The intervention was delivered in community setting s. Participants People with PD , with a history of two or more falls in the previous year , who were able to mobilise independently . Intervention 10 week , physiotherapy led , group delivered strength and balance training programme with supplementary home exercises ( intervention ) or usual care ( control ) . Main outcome measure Number of falls during the ( a ) 10 week intervention period and ( b ) the 10 week follow-up period . Results 130 people were recruited and r and omised ( 64 to the intervention ; 66 to usual care ) . Seven participants ( 5.4 % ) did not complete the study . The incidence rate ratio for falls was 0.68 ( 95 % CI 0.43 to 1.07 , p=0.10 ) during the intervention period and 0.74 ( 95 % CI 0.41 to 1.33 , p=0.31 ) during the follow-up period . Statistically significant between group differences were observed in Berg balance , Falls Efficacy Scale-International scores and recreational physical activity levels . Conclusions The study did not demonstrate a statistically significant between group difference in falls although the difference could be considered clinical ly significant . However , a type 2 error can not be ruled out . The findings from this trial add to the evidence base for physiotherapy and exercise in the management of people with PD . Trial registration IS RCT N50793425", "AIM This study aim ed to evaluate the feasibility and cultural considerations of a minimally supervised , home-based exercise program in Jordan . METHODS Quantitative and qualitative approaches were used . Thirty participants were r and omly allocated to either an 8-week intervention group ( n = 16 ) , or a st and ard care group ( n = 14 ) . The intervention incorporated the home use of an exercise DVD , walking program and initial instructional sessions and weekly phone calls provided by a physiotherapist . Interviews were used to explore feasibility . Unified Parkinson 's disease rating scale ( UPDRS-III ) ; balance and walking speed were assessed . RESULTS The retention rate was 86.7 % and mean adherence rate was 77 % . Personal and sociocultural barriers of adherence to the exercise program were identified . UPDRS-III at follow-up was lower in the intervention group . CONCLUSION A home exercise program was feasible . Sociocultural barriers specific to Arabic culture may affect the uptake of such an intervention in Parkinson 's disease in these countries", "Objectives : To determine long-term effects of a highly challenging training program in people with Parkinson ’s disease , as well as describe how initially observed improvements of the program deteriorated over time . Design : Long-term follow-up of previously reported outcomes at 10 weeks of a r and omized controlled trial . Setting : University hospital setting . Participants : One-hundred elderly with mild-to-moderate ( Hoehn and Yahr 2–3 ) Parkinson ’s disease . Interventions : Participants in the training group ( n = 51 ) received 10 weeks ( three times/week ) of balance and gait exercises , incorporating dual-tasks , while the control group ( n = 49 ) received care as usual . Main Outcome Measures : Balance control ( Mini-Balance Evaluation System Test ( Mini-BESTest ) ) and gait velocity . Mixed- design analyses of variance were used to determine potential training effects at 6- and 12-month follow-up , and piecewise regression models predicted the rate of deterioration . Results : Seventy-six participants were included at final follow-up . No significant ( P > .05 ) between-group differences remained at either 6 or 12 months following the intervention . The mean Mini-BESTest scores of the training and control group were 19.9 ( SD 4.4 ) and 18.6 ( SD 4.3 ) , respectively , at the 12-month follow-up . Gait speed was 1.2 ( SD 0.2 ) m/s in both groups at 12 months . The training group showed a larger deterioration rate per month in balance performance ( 0.21 point ) and gait velocity ( 0.65 cm/s ) than controls ( P < .05 ) . Conclusion : These results suggest that training effects diminish within 6 months after balance training , implying that the program may need to be repeated regularly", "Objective To examine mortality and associated risk factors , including possible effects of mild cognitive impairment , imaging , and CSF abnormalities , in a community-based population with incident parkinsonism and Parkinson disease . Methods One hundred eighty-two patients with new-onset , idiopathic parkinsonism were diagnosed from January 2004 through April 2009 , in a catchment area of 142,000 inhabitants in Sweden . Patients were comprehensively investigated according to a multimodal research protocol and followed prospect ively for up to 13.5 years . A total of 109 patients died . Mortality rates in the general Swedish population were used to calculate st and ardized mortality ratio and expected survival , and Cox proportional hazard models were used to investigate independent predictors of mortality . Results The st and ardized mortality ratio for all patients was 1.84 ( 95 % confidence interval 1.50–2.22 , p Patients with atypical parkinsonism ( multiple system atrophy or progressive supranuclear palsy ) had the highest mortality . In early Parkinson disease , a mild cognitive impairment diagnosis , freezing of gait , hyposmia , reduced dopamine transporter activity in the cau date , and elevated leukocytes in the CSF were significantly associated with shorter survival . Conclusion Although patients presenting with idiopathic parkinsonism have reduced survival , the survival is highly dependent on the type and characteristics of the parkinsonian disorder . Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy . The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implication", "Objective To estimate the effect of a physiotherapist-delivered fall prevention programme for people with Parkinson ’s ( PwP ) . Methods People at risk of falls with confirmed Parkinson ’s were recruited to this multicentre , pragmatic , investigator blind , individually r and omised controlled trial with prespecified subgroup analyses . 474 PwP ( Hoehn and Yahr 1–4 ) were r and omised : 238 allocated to a physiotherapy programme and 236 to control . All participants had routine care ; the control group received a DVD about Parkinson ’s and single advice session at trial completion . The intervention group ( PDSAFE ) had an individually tailored , progressive home-based fall avoidance strategy training programme with balance and strengthening exercises . The primary outcome was risk of repeat falling , collected by self-report monthly diaries , 0–6 months after r and omisation . Secondary outcomes included Mini-BESTest for balance , chair st and test , falls efficacy , freezing of gait , health-related quality of life ( EuroQol EQ-5D ) , Geriatric Depression Scale , Physical Activity Scale for the Elderly and Parkinson ’s Disease Question naire , fractures and rate of near falling . Results Average age is 72 years and 266 ( 56 % ) were men . By 6 months , 116 ( 55 % ) of the control group and 125 ( 61.5 % ) of the intervention group reported repeat falls ( controlled OR 1.21 , 95 % CI 0.74 to 1.98 , p=0.447 ) . Secondary subgroup analyses suggested a different response to the intervention between moderate and severe disease severity groups . Balance , falls efficacy and chair st and time improved with near falls reduced in the intervention arm . Conclusion PDSAFE did not reduce falling in this pragmatic trial of PwP. Other functional tasks improved and reduced fall rates were apparent among those with moderate disease . Trial registration number IS RCT N48152791" ]

[ "Obese AT ( adipose tissue ) exhibits increased macrophage number . Pro-inflammatory CD16 + peripheral monocyte numbers are also reported to increase with obesity . The present study was undertaken to simultaneously investigate obesity-associated changes in CD16 + monocytes and ATMs ( AT macrophages ) . In addition , a pilot r and omized placebo controlled trial using the PPAR ( peroxisome-proliferator-activated receptor ) agonists , pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16 + monocytes , ATM and cardiometabolic and adipose dysfunction indices . Obese glucose-tolerant men ( n=28 ) were r and omized to placebo , pioglitazone ( 30 mg/day ) and fenofibrate ( 160 mg/day ) for 12 weeks . A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16 + monocyte levels via flow cytometry . A subcutaneous AT biopsy was performed to determine adipocyte cell surface and ATM number , the latter was determined via assessment of CD68 expression by IHC ( immunohistochemistry ) and real-time PCR . Subcutaneous AT mRNA expression of CEBPβ ( CCAAT enhancer-binding protein β ) , SREBP1c ( sterol-regulatory-element-binding protein 1c ) , PPARγ2 , IRS-1 ( insulin receptor substrate-1 ) , GLUT4 ( glucose transporter type 4 ) and TNFα ( tumour necrosis factor α ) were also assessed . Comparisons were made between obese and lean controls ( n=16 ) at baseline , and pre- and post-PPAR agonist treatment . Obese individuals had significantly increased adipocyte cell surface , percentage CD14+/CD16 + monocyte numbers and ATM number ( all P=0.0001 ) . Additionally , serum TNF-α levels were significantly elevated ( P=0.017 ) and adiponectin levels reduced ( total : P=0.0001 ; high : P=0.022 ) with obesity . ATM number and percentage of CD14+/CD16 + monocytes correlated significantly ( P=0.05 ) . Pioglitazone improved adiponectin levels significantly ( P=0.0001 ) , and result ed in the further significant enlargement of adipocytes ( P=0.05 ) , without effect on the percentage CD14+/CD16 + or ATM number . Pioglitazone treatment also significantly increased subcutaneous AT expression of CEBPβ mRNA . The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels , supports the central ity of AT to the cardiometabolic derangement underlying the development of T2D ( Type 2 diabetes ) and CVD ( cardiovascular disease )", "The insulin-sensitizing effects of thiazolidinediones are thought to be mediated through peroxisome proliferator-activated receptor-gamma , a nuclear receptor that is highly abundant in adipose tissue . It has been reported that adipocytes secrete a variety of proteins , including tumor necrosis factor-alpha , resistin , plasminogen activator inhibitor-1 , and adiponectin . Adiponectin is a fat cell-secreted protein that has been reported to increase fat oxidation and improve insulin sensitivity . Our aim was to study the effects of troglitazone on adiponectin levels in lean , obese , and diabetic subjects . Ten diabetic and 17 nondiabetic subjects ( 8 lean , BMI 27 kg/m(2 ) ) participated in the study . All subjects underwent an 80 mU. m(-2 ) . min(-1 ) hyperinsulinemic-euglycemic glucose clamp before and after 3 months ' treatment with the thiazolidinedione ( TZD ) troglitazone ( 600 mg/day ) . Fasting plasma glucose significantly decreased in the diabetic group after 12 weeks of treatment compared with baseline ( 9.1 + /- 0.9 vs. 11.1 + /- 0.9 mmol/l , P Fasting insulin for the entire group was significantly lower than baseline ( P = 0.02 ) after treatment . At baseline , glucose disposal rate ( R(d ) ) was lower in the diabetic subjects ( 3.4 + /- 0.5 mg . kg(-1 ) . min(-1 ) ) than in the lean ( 12.3 + /- 0.4 ) or obese subjects ( 6.7 + /- 0.7 ) ( P Baseline adiponectin levels were significantly lower in the diabetic than the lean subjects ( 9.0 + /- 1.7 vs. 16.7 + /- 2.7 micro g/ml , P = 0.03 ) and rose uniformly in all subjects ( 12.2 + /- 2.3 vs. 25.7 + /- 2.6 micro g/ml , P adiponectin levels were suppressed below basal levels in all groups ( 10.2 + /- 2.3 vs. 12.2 + /- 2.3 micro g/ml , P Adiponectin levels correlated with R(d ) ( r = 0.46 , P = 0.016 ) and HDL cholesterol levels ( r = 0.59 , P fasting insulin ( r = -0.39 , P = 0.042 ) and plasma triglyceride ( r = -0.61 , P TZD treatment increased adiponectin levels in all subjects , including normal subjects in which no other effects of TZDs are observed . Insulin also appears to suppress adiponectin levels . We have confirmed these results in normal rats . These findings suggest that adiponectin can be regulated by obesity , diabetes , TZDs , and insulin , and it may play a physiologic role in enhancing insulin sensitivity", "OBJECTIVE Improvement in endothelial function is predicted to improve insulin sensitivity , and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease . We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity . RESEARCH DESIGN AND METHODS We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia ( 24 had metabolic syndrome ) . This study was r and omized , double blind , placebo controlled , and crossover in design . RESULTS Compared with placebo , fenofibrate decreased total cholesterol , non-HDL cholesterol , apolipoprotein B , and triglycerides and increased HDL cholesterol and apolipoprotein A-I ( all P LDL cholesterol ( P = 0.069 ) . Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 + /- 5 % ( P plasma levels of high-sensitivity C-reactive protein ( hsCRP ) relative to baseline measurements from 0.80 to 0.70 mg/l ( P = 0.001 ) and fibrinogen levels by 16 + /- 3 % ( P placebo , fenofibrate therapy significantly increased plasma levels of adiponectin by 14 + /- 5 % ( P = 0.008 ) and increased insulin sensitivity ( assessed by quantitative insulin sensitivity check index [ QUICKI ] ) by 6 + /- 2 % ( P = 0.048 ) . There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation ( r = 0.401 , P = 0.006 ) , hsCRP ( r = -0.443 , P = 0.002 ) , or QUICKI ( r = 0.292 , P = 0.049 ) . Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation ( r = 0.504 , P = 0.013 ) . Overall , we observed similar results in 24 patients with metabolic syndrome . CONCLUSIONS Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia , reduced inflammation marker levels , increased adiponectin levels , and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients", "Objective . To examine the effect of acute and short-term ( ~1 week ) aerobic exercise training on plasma adiponectin levels in inactive , abdominally obese men . Material s and Methods . Inactive and abdominally obese men ( n = 38 , waist circumference ≥102 cm ) recruited from Kingston , Canada were r and omly allocated to perform three bouts of aerobic treadmill exercise at either low ( 50 % VO2 peak ) or high ( 75 % VO2 peak ) intensity during a 1-week period . Blood sample s were taken before and after the first exercise session and 24–72 hours following the completion of the final exercise session . Results . Adiponectin levels were elevated immediately following an acute bout of exercise at both high and low intensities ( High : 5.79 ± 0.42 versus 5.05 ± 0.41 ug/mL ; Low : 5.24 ± 0.44 versus 4.37 ± 0.44 ug/mL , P to baseline , adiponectin levels were also elevated 24–72 hours following the final exercise session ( High : 5.47 ± 0.48 versus 4.88 ± 0.48 ug/mL ; Low : 5.18 ± 0.49 versus 4.47 ± 0.49 ug/mL , P Both acute and short-term aerobic exercise result in a significant increase in plasma adiponectin levels in inactive , abdominally obese men independent of intensity", "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 .", "CONTEXT HIV patients on antiretroviral therapy ( ART ) have a unique dyslipidemia [ elevated triglycerides and non-high-density lipoprotein-cholesterol ( HDL-C ) , low HDL-C ] with insulin resistance ( characterized by hypoadiponectinemia ) . OBJECTIVE The aim was to test a targeted , comprehensive , additive approach to treating the dyslipidemia . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled , 24-wk trial of lifestyle modification , fenofibrate , and niacin in multiethnic HIV clinics at an academic center . PARTICIPANTS Hypertriglyceridemic adult patients were stratified on three combinations of ART classes . Subjects retained at the first measurement ( 2 wk ) after entry were included in the analysis ( n = 191 ) . INTERVENTIONS Subjects were r and omized into five treatment groups : usual care ( group 1 ) ; low-saturated-fat diet and exercise ( D/E ; group 2 ) ; D/E + fenofibrate ( group 3 ) ; D/E + niacin ( group 4 ) ; or D/E + fenofibrate + niacin ( group 5 ) . MAIN OUTCOME MEASURES We measured changes in fasting triglycerides , HDL-C , and non-HDL-C ( primary ) , and in insulin sensitivity , glycemia , adiponectin , C-reactive protein , energy expenditure , and body composition ( secondary ) . Data were analyzed as a factorial set of treatment combinations using a mixed repeated measures model , last observation carried forward , and complete case approaches ( groups 2 - 5 ) , and as an unstructured set of treatments ( groups 1 - 5 ) . RESULTS Fenofibrate improved triglycerides ( P = 0.002 ) , total cholesterol ( P = 0.02 ) , and non-HDL-C ( P = 0.003 ) , whereas niacin improved HDL-C ( P = 0.03 ) , and both drugs decreased the total cholesterol-to-HDL-C ratio ( P = 0.005 - 0.01 ) . The combination of D/E , fenofibrate , and niacin provided maximal benefit , markedly reducing triglycerides ( -52 % compared to usual care ; P = 0.003 ) , increasing HDL-C ( + 12 % ; P non-HDL-C ( -18.5 % ; P = 0.003 ) and total cholesterol-to-HDL-C ratio ( -24.5 % ; P HDL-C , decreasing non-HDL-C and hypertriglyceridemia , and ameliorating hypoadiponectinemia in patients with HIV/ART-associated dyslipidemia", "BACKGROUND Coronary heart disease patients with low high-density lipoprotein cholesterol ( HDL-C ) levels , high triglyceride levels , or both are at an increased risk of cardiovascular events , but the clinical impact of raising HDL-C or decreasing triglycerides remains to be confirmed . METHODS AND RESULTS In a double-blind trial , 3090 patients with a previous myocardial infa rct ion or stable angina , total cholesterol of 180 to 250 mg/dL , HDL-C to receive either 400 mg of bezafibrate per day or a placebo ; they were followed for a mean of 6.2 years . The primary end point was fatal or nonfatal myocardial infa rct ion or sudden death . Bezafibrate increased HDL-C by 18 % and reduced triglycerides by 21 % . The frequency of the primary end point was 13 . 6 % on bezafibrate versus 15.0 % on placebo ( P=0.26 ) . After 6.2 years , the reduction in the cumulative probability of the primary end point was 7.3 % , ( P=0.24 ) . In a post hoc analysis in the subgroup with high baseline triglycerides ( > or = 200 mg/dL ) , the reduction in the cumulative probability of the primary end point by bezafibrate was 39.5 % ( P=0.02 ) . Total and noncardiac mortality rates were similar , and adverse events and cancer were equally distributed . CONCLUSIONS Bezafibrate was safe and effective in elevating HDL-C levels and lowering triglycerides . An overall trend in a reduction of the incidence of primary end points was observed . The reduction in the primary end point in patients with high baseline triglycerides ( > or = 200 mg/dL ) requires further confirmation", "CONTEXT Adiponectin , a recently discovered adipocyte-derived peptide , is involved in the regulation of insulin sensitivity and lipid oxidation and , purportedly , in the development of atherosclerosis and coronary heart disease in humans . OBJECTIVE To assess prospect ively whether plasma adiponectin concentrations are associated with risk of myocardial infa rct ion ( MI ) . DESIGN , SETTING , AND PARTICIPANTS Nested case-control study among 18 225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw ( 1993 - 1995 ) . During 6 years of follow-up through January 31 , 2000 , 266 men subsequently developed nonfatal MI or fatal coronary heart disease . Using risk set sampling , controls were selected in a 2:1 ratio matched for age , date of blood draw , and smoking status ( n = 532 ) . MAIN OUTCOME MEASURE Incidence of nonfatal MI and fatal coronary heart disease by adiponectin level . RESULTS After adjustment for matched variables , participants in the highest compared with the lowest quintile of adiponectin levels had a significantly decreased risk of MI ( relative risk [ RR ] , 0.39 ; 95 % confidence interval [ CI ] , 0.23 - 0.64 ; P for trend hemoglobin A1c or C-reactive protein levels also had little impact , but additional adjustment for low- and high-density lipoprotein cholesterol levels modestly attenuated this association ( RR , 0.56 ; 95 % CI , 0.32 - 0.99 ; P for trend = .02 ) . CONCLUSIONS High plasma adiponectin concentrations are associated with lower risk of MI in men . This relationship can be only partly explained by differences in blood lipids and is independent of inflammation and glycemic status", "PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance , but their effects on insulin sensitivity in humans are less clear . We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate . At baseline , body mass index , serum glucose , triglycerides , glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes , while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group ( n=10 ) . No differences were found in serum resistin levels between obese and control group . Fenofibrate treatment decreased serum triglyceride concentrations , while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration . Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment . All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration . We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus . The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle", "BACKGROUND Omega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia . However , a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published . METHODS This was a r and omized , single-blind , placebo-controlled , parallel study . Age , sex , and body mass index were matched among groups . All patients were recommended to maintain a low fat diet . Fifty patients in each group were given placebo , omega-3 fatty acids 2 g ( most commonly used dosage in Korean patients ) , or fenofibrate 160 mg , respectively daily for 2 months . RESULTS Omega-3 fatty acids therapy decreased triglycerides by 21 % and triglycerides/HDL cholesterol and improved flow-mediated dilation ( P insulin , plasma adiponectin levels , and insulin sensitivity ( determined by QUICKI ) relative to baseline measurements . Fenofibrate therapy decreased total cholesterol , triglycerides by 29 % , and triglycerides/HDL-cholesterol ( all P flow-mediated dilation when compared with baseline . When compared with placebo and omega-3 fatty acids , fenofibrate therapy decreased non-HDL cholesterol ( P triglycerides/HDL cholesterol ( P=0.016 ) while increasing HDL cholesterol ( P apolipoprotein AI ( P=0.001 ) . Of note , when compared with omega-3 fatty acids , fenofibrate therapy decreased fasting insulin ( P=0.023 ) and increased plasma adiponectin ( P=0.002 ) and insulin sensitivity ( P=0.015 ) . CONCLUSIONS Omega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation . However , fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia", "BACKGROUND Development of insulin resistance ( IR ) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus . Few data are available regarding the short-term efficacy of the peroxisome proliferator-activated receptor lig and bezafibrate on IR , and its long-term effect is unknown . The present analysis aim ed to investigate the effect of bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infa rct ion Prevention Study . METHODS Metabolic and inflammatory parameters were analyzed from stored frozen plasma sample s obtained from patients who completed a 2-year , r and omized , double-blind , placebo-controlled study . The homeostatic indexes of IR ( HOMA-IRs ) were calculated according to the homeostasis model of assessment . RESULTS Both the patients taking bezafibrate ( n = 1262 ) and those taking placebo ( n = 1242 ) displayed similar baseline characteristics . The HOMA-IRs significantly correlated at baseline and during follow-up with glucose ( r = 0.35 and 0.31 , respectively ) and triglycerides ( r = 0.16 and 0.19 , respectively ) . In a subgroup of 351 patients with diabetes , HOMA-IR at baseline was 88 % higher than in their counterparts with normal glucose levels ( P placebo group , during follow-up there was a significant 34.4 % rise in HOMA-IR . In contrast , in the bezafibrate group there was only a nonsignificant 6.6 % change in HOMA-IR . The intergroup differences in percentage changes of HOMA-IR were in favor of bezafibrate ( P patients with coronary artery disease enrolled in our study , as represented by the placebo group , HOMA-IR increased over time . During the 2 years of the follow-up , bezafibrate significantly attenuated this process", "Background —Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism . Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown . The goal of this study was to evaluate the effect of the peroxisome proliferator – activated receptor lig and bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period . Methods and Results —The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL ( 6.1 to 6.9 mmol/L ) . The patients received either 400 mg bezafibrate retard ( 156 patients ) or placebo ( 147 patients ) once a day . No patients were using statins , and use of ACE inhibitors , which also reduce diabetes incidence , was relatively low . During follow-up , development of new-onset diabetes was recorded in 146 patients : in 80 ( 54.4 % ) from the placebo group and 66 ( 42.3 % ) from the bezafibrate group ( P = 0.04 ) . The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo : 4.6±2.3 versus 3.8±2.6 years ( P = 0.004 ) . Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development ( hazard ratio , 0.70 ; 95 % CI , 0.49 to 0.99 ) . Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level ( hazard ratio , 1.22 ; 95 % CI 1.0 to 1.51 ) and body mass index ( hazard ratio , 1.10 ; 95 % CI , 1.05 to 1.16 ) . Conclusions —Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose . Whether the combination of bezafibrate with other recommended drugs for secondary prevention ( statins and ACE inhibitors ) would be as efficacious as suggested by our results remains to be determined", "OBJECTIVE Elevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects . We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function , and the corresponding responses to fenofibrate treatment . METHODS Plasma apolipoprotein ( apo ) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM . Flow-mediated endothelium-dependent dilation ( FMD ) and glyceryl-trinitrate mediated dilatation ( GTNMD ) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique . RESULTS In univariate analysis , plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD ( r = -0.425 and -0.423 , respectively , P GTNMD . In regression models including BMI and HOMA score , plasma apoB-48 was an independent predictors ( P brachial artery FMD ( β coefficient = -0.384 ) . Replacing HOMA-IR score with plasma triglyceride , adiponectin or CRP concentrations did not alter the findings . The subjects were then r and omized to a 12-week treatment period of either 200 mg micronized fenofibrate or matching placebo . Compared with the placebo group , fenofibrate treatment ( 200 mg daily for 12 weeks ) achieved significant increase in FMD ( + 34 % ) and reduction in plasma triglyceride ( -42 % ) , apoB-48 ( -52 % ) and RLP-cholesterol ( -51 % ) concentrations . The increase in FMD with fenofibrate was significantly associated with the corresponding decrease in plasma apoB-48 ( r = -0.644 , P improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function", "A double-blind , placebo-controlled trial assessed the effect of a slow-release formulation of bezafibrate ( Bezalip Mono , 400 mg daily for 3 months ) on lipid profile , glucose homeostasis , platelet function , and plasma fibrinogen concentration in non-insulin-dependent ( type II ) diabetics . Twenty-four patients completed the trial . There was a significant improvement in the cholesterol ( p triglyceride ( p and nonesterified fatty acid ( p concentrations and in the fasting blood glucose ( p glycosylated hemoglobin ( p levels of those ( n = 11 ) who received the active preparation but not in those ( n = 13 ) who received placebo . Treatment , but not placebo , also result ed in a significant ( p plasma fibrinogen concentration and a trend towards inhibition of platelet aggregation . Bezafibrate was well tolerated ; only one patient ( not included in the analysis of results ) withdrew from the trial possibly because of side effects of the drug . A larger study is needed to establish whether bezafibrate can reduce nonlipid risk factors ( e.g. , plasma fibrinogen concentration , glucose intolerance , and hyperinsulinemia ) in normo- and hyperlipidemic subjects", "Obesity is a low grade inflammatory state associated with premature cardiovascular morbidity and mortality . Along with traditional risk factors the measurement of endothelial function , insulin resistance , inflammation and arterial stiffness may contribute to the assessment of cardiovascular risk . We conducted a r and omised placebo controlled trial to assess the effects of 12 weeks treatment with a PPAR alpha agonist ( fenofibrate ) and a PPAR gamma agonist ( pioglitazone ) on these parameters in obese glucose tolerant men . Arterial stiffness was measured using augmentation index and pulse wave velocity ( PWV ) . E-selectin , VCAM-1 and ICAM-1 were used as markers of endothelial function . Insulin sensitivity improved with pioglitazone treatment ( p=0.001 ) and , in keeping with this , adiponectin increased by 85.2 % ( p Pro-inflammatory cytokine levels ( TNFalpha , IL-6 and IL-1 beta ) fell with both treatments ( p VCAM-1 and ICAM-1 were reduced with both treatments ( p E-selectin improved with pioglitazone treatment ( p=0.05 ) . Both treatments result ed in a fall in augmentation index . PWV fell by 17.4 % with fenofibrate treatment ( p pioglitazone treatment ( p Pioglitazone and fenofibrate treatment of obese , glucose tolerant men reduces inflammation , improves markers of endothelial function and reduces arterial stiffness . These results suggest that treatment with PPAR agonists has potential to reduce the incidence of premature cardiovascular disease associated with obesity", "BACKGROUND Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease , partly owing to dyslipidaemia , which can be amenable to fibrate therapy . We design ed the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study to assess the effect of fenofibrate on cardiovascular disease events in these patients . METHODS We did a multinational , r and omised controlled trial with 9795 participants aged 50 - 75 years , with type 2 diabetes mellitus , and not taking statin therapy at study entry . After a placebo and a fenofibrate run-in phase , we r and omly assigned patients ( 2131 with previous cardiovascular disease and 7664 without ) with a total-cholesterol concentration of 3.0 - 6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0 - 5.0 mmol/L to micronised fenofibrate 200 mg daily ( n=4895 ) or matching placebo ( n=4900 ) . Our primary outcome was coronary events ( coronary heart disease death or non-fatal myocardial infa rct ion ) ; the outcome for prespecified subgroup analyses was total cardiovascular events ( the composite of cardiovascular death , myocardial infa rct ion , stroke , and coronary and carotid revascularisation ) . Analysis was by intention to treat . The study was prospect ively registered ( number IS RCT N 64783481 ) . FINDINGS Vital status was confirmed on all but 22 patients . Averaged over the 5 years ' study duration , similar proportions in each group discontinued study medication ( 10 % placebo vs 11 % fenofibrate ) and more patients allocated placebo ( 17 % ) than fenofibrate ( 8 % ; p coronary event ( relative reduction of 11 % ; hazard ratio [ HR ] 0.89 , 95 % CI 0.75 - 1.05 ; p=0.16 ) . This finding corresponds to a significant 24 % reduction in non-fatal myocardial infa rct ion ( 0.76 , 0.62 - 0.94 ; p=0.010 ) and a non-significant increase in coronary heart disease mortality ( 1.19 , 0.90 - 1.57 ; p=0.22 ) . Total cardiovascular disease events were significantly reduced from 13.9 % to 12.5 % ( 0.89 , 0.80 - 0.99 ; p=0.035 ) . This finding included a 21 % reduction in coronary revascularisation ( 0.79 , 0.68 - 0.93 ; p=0.003 ) . Total mortality was 6.6 % in the placebo group and 7.3 % in the fenofibrate group ( p=0.18 ) . Fenofibrate was associated with less albuminuria progression ( p=0.002 ) , and less retinopathy needing laser treatment ( 5.2%vs 3.6 % , p=0.0003 ) . There was a slight increase in pancreatitis ( 0.5%vs 0.8 % , p=0.031 ) and pulmonary embolism ( 0.7%vs 1.1 % , p=0.022 ) , but no other significant adverse effects . INTERPRETATION Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events . It did reduce total cardiovascular events , mainly due to fewer non-fatal myocardial infa rct ions and revascularisations . The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit", "BACKGROUND We investigated effects of fenofibrate therapy on endothelial dysfunction and adipocytokine profiles . METHODS A r and omized , single-blind , placebo-controlled , cross-over study was conducted in 53 patients with primary hypertriglyceridemia . We administered placebo or fenofibrate 160 mg daily for 8 weeks . RESULTS When compared with placebo , fenofibrate therapy substantially lowered plasma levels of TNF-α by 6±3 % ( P=0.014 ) and hsCRP from 1.10 to 0.90mg/l ( P=0.004 ) . When compared with placebo , fenofibrate therapy increased plasma levels of adiponectin by 17±4 % ( P=0.001 ) , insulin sensitivity by 4±1 % ( as assessed by QUICKI , P=0.009 ) , and decreased plasma levels of leptin and resistin by 4±7 % ( P=0.022 ) and 10±3 % ( P=0.001 ) , respectively . There were correlations between percent changes in QUICKI and percent changes in adiponectin levels ( r=0.279 , P=0.043 ) or leptin ( r=-0.280 , P=0.042 ) . CONCLUSIONS Fenofibrate therapy significantly reduced pro-inflammatory biomarkers and improved adipocytokines levels and insulin sensitivity in hypertriglyceridemic patients" ]

[ "Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people . Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the calcium – vitamin D3 fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women", "Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896", "BACKGROUND Despite considerable interest , the relationship between circulating 25-hydroxyvitamin D and the risk of hip fracture is not fully established . OBJECTIVE The objective of the study was to study the association between serum 25-hydroxyvitamin D concentrations [ s-25(OH)D ] and the risk of hip fracture in Norway , a high-latitude country that has some of the highest hip fracture rates worldwide . METHODS A total of 21 774 men and women aged 65 - 79 years attended 4 community-based health studies during 1994 - 2001 . Information on subsequent hip fractures was retrieved from electronic hospital discharge registers , with a maximum follow-up of 10.7 years . Using a stratified case-cohort design , s-25(OH)D was determined by HPLC-atmospheric pressure chemical ionization-mass spectrometry in stored serum sample s in hip fracture cases ( n = 1175 ; 307 men , 868 women ) and in gender-stratified r and om sample s ( n = 1438 ) . Cox proportional hazards regression adapted for the case-cohort design was performed . RESULTS We observed an inverse association between s-25(OH)D and hip fracture ; those with s-25(OH)D in the lowest quartile ( risk of hip fracture compared with the highest quartile ( ≥67.9 nmol/L ) in a model accounting for age , gender , study center , and body mass index . The association was stronger in men than in women : hazard ratio 1.65 ( 95 % CI 1.04 - 2.61 ) vs hazard ratio 1.25 ( 95 % CI 0.95 - 1.65 ) . CONCLUSION In this prospect i ve case-cohort study of hip fractures , the largest ever reported , we found an increased risk of hip fracture in subjects in the lowest compared with the highest quartile of serum 25-hydroxyvitamin D. In accordance with the findings of previous community-based studies , low vitamin D status was a modest risk factor for hip fracture", "OBJECTIVES To determine the efficacy and safety of high-dose vitamin D supplementation for prevention of acute respiratory infection ( ARI ) in older long-term care residents . DESIGN R and omized controlled trial investigating high-dose vs st and ard-dose vitamin D from 2010 to 2014 . SETTING Colorado long-term care facilities . PARTICIPANTS Long-term care residents aged 60 and older ( n = 107 ) . INTERVENTION The high-dose group received monthly supplement of vitamin D3 100,000 IU , the st and ard-dose group received a monthly placebo ( for participants taking 400 - 1,000 IU/d as part of usual care ) or a monthly supplement of 12,000 IU of vitamin D3 ( for participants taking incidence of ARI during the 12-month intervention . Secondary outcomes were falls and fractures , 25-hydroxyvitamin D levels , hypercalcemia , and kidney stones . RESULTS Participants ( 55 high dose , 52 st and ard dose ) were r and omized and included in the final analysis . The high-dose group had 0.67 ARIs per person-year and the st and ard-dose group had 1.11 ( incidence rate ratio ( IRR ) = 0.60 , 95 % confidence interval ( CI ) = 0.38 - 0.94 , P = .02 ) . Falls were more common in the high-dose group ( 1.47 per person-year vs 0.63 in st and ard-dose group ; IRR = 2.33 , 95 % CI = 1.49 - 3.63 , P Fractures were uncommon and similar in both groups ( high dose 0.10 vs st and ard dose 0.19 per person-year ; P = .31 ) . Mean trough 25-hydroxyvitamin D levels during the trial were 32 . ng/mL in the high-dose group and 25.1 ng/mL in the st and ard-dose group . There was no hypercalcemia or kidney stones in either group . CONCLUSION Monthly high-dose vitamin D3 supplementation reduced the incidence of ARI in older long-term care residents but was associated with a higher rate of falls without an increase in fractures ", "Introduction Osteoporotic fractures in older people are a major and increasing public health problem . We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation . Methods In a pragmatic double blind r and omised controlled trial of 3 years duration , we examined 3,440 people ( 2,624 women and 816 men ) living in residential or care home . We used four-monthly oral supplementation using 100,000 IU vitamin D2 ( ergocalciferol ) . As a main outcome measure , we used the incidence of first fracture using an intention to treat analysis . This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales , UK . Results The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up ( 7 fractures per 100 people per year of follow-up ) , with 218 first fractures in the control group over 2,860 person years of follow-up . The hazard ratio of 0.95 ( 95 % confidence interval 0.79–1.15 ) for intervention compared to control was not statistically significant . ConclusionS upplementation with four-monthly 100,000 IU of oral vitamin D2 is not sufficient to affect fracture incidence among older people living in institutional care", "Summary This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status . The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks , and this dose should be tested in future trials for fracture prevention . Introduction The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU ( 100 μg ) , 2000 IU ( 50 μg ) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes . Methods This is a r and omized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire , UK . Outcomes included biochemical markers of vitamin D status ( plasma 25-hydroxy-vitamin D [ 25[OH]D ] , parathyroid hormone [ PTH ] , calcium and alkaline phosphatase ) , cardiovascular risk factors and tests of physical function . Results Mean ( SD ) plasma 25(OH)D levels were 50 ( 18 ) nmol/L at baseline and increased to 137 ( 39 ) , 102 ( 25 ) and 53 ( 16 ) nmol/L after 12 months in those allocated 4000 IU , 2000 IU or placebo , respectively ( with 88 % , 70 % and 1 % of these groups achieving the pre-specified level of > 90 nmol/L ) . Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium . The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index , for which the further increase was smaller in overweight and obese participants compared with normal-weight participants . Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function . Conclusions After accounting for average 70 % compliance in long-term trials , doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies", "UNLABELLED This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D , especially during winter periods . INTRODUCTION We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents . MATERIAL S AND METHODS This was a factorial , cluster-r and omized , pragmatic , intervention study . We included 9605 community-dwelling residents aged 66 + years . We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU ( 10 microg ) of vitamin D3 to a total of 4957 participants . Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants . Both programs included revision of the resident 's current pharmaceutical treatment . We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Data base . We defined osteoporotic fractures as low energy fractures of the proximal humerus , distal forearm , vertebral column , pelvis , cervical femur , and intertrochanteric femur . RESULTS Active participation was 50.3 % in the Calcium and Vitamin D Program and 46.4 % in the Environmental and Health Program . We observed a 16 % reduction in fracture incidence rate ( relative risk [ RR ] , 0.84 ; CI , 0.72 - 0.98 ; p female residents offered the Calcium and Vitamin D Program ( intention-to-prevent analysis ) . CONCLUSIONS This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D , especially during winter periods", "In previous studies , we demonstrated that 12-month treatment with 0.75μg/day eldecalcitol increased bone mineral density in osteoporotic patients regardless of serum 25-hydroxyvitamin D ( 25(OH)D ) level , and in a 3-year r and omized double-blind clinical trial , eldecalcitol significantly reduced the incidences of vertebral and wrist fractures compared to alfacalcidol . However , it remains unclear whether the fracture risk reduction by eldecalcitol is affected by serum 25(OH)D. In the fracture prevention trial , patients with low 25(OH)D level at baseline were supplemented with 400IU/day native vitamin D3 . In the current study , patients from that trial were divided according to the tertiles of serum 25(OH)D level at 6 months after treatment initiation . The increases in lumbar and hip BMD by eldecalcitol were significantly higher in all tertiles than those by alfacalcidol . The incidences of vertebral and osteoporotic fractures tended to be lower in each tertile of the eldecalcitol-treated group than in the corresponding tertile of the alfacalcidol-treated group , with the exception of vertebral fractures in the low tertile . We also investigated whether eldecalcitol treatment affected levels of serum 25(OH)D , serum 1,25(OH)2D , and parathyroid hormone in patients without vitamin D supplementation . With eldecalcitol treatment , serum 1,25(OH)2D concentration was reduced by approximately 50 % , whereas serum levels of parathyroid hormone and 25(OH)D were not affected . The major findings of the present study were that eldecalcitol did not affect serum 25(OH)D levels , and that it reduced the incidence of osteoporotic fractures and increased BMD in comparison with alfacalcidol regardless of serum 25(OH)D level within the range of serum 25(OH)D concentrations at or higher than 20ng/mL. Whether eldecalcitol is similarly effective at vitamin D deficient serum 25(OH)D levels remains to be clarified . This article is part of a Special Issue entitled ' Vitamin D Workshop '", "Conflicting data regarding cardiovascular effects of thiazolidinediones ( TZDs ) and extra-skeletal effects of vitamin D supported the need for a definitive trial . The Thiazolidinedione Intervention with vitamin D Evaluation ( TIDE ) trial aim ed to assess the effects of TZDs ( rosiglitazone and pioglitazone ) on cardiovascular outcomes and the effects of vitamin D ( cholecalciferol ) on cancers and mortality . A large multicentre 3 × 2 factorial double-blind placebo-controlled r and omised trial recruited from outpatient primary care and specialty clinics in 33 countries . From June 2009 to July 2010 , 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥50 years whose HbA1c was 6.5–9.5 % ( 48–80 mmol/mol ) when using two or fewer glucose-lowering drugs were r and omised by a central computer system to placebo ( n = 541 ) , rosiglitazone 4–8 mg/day ( n = 399 ) or pioglitazone 30–45 mg/day ( n = 392 ) ; 1,221 participants were r and omised to placebo ( n = 614 ) or vitamin D 1,000 IU/day ( n = 607 ) . Participants and all study personnel were blind to treatment allocation . The primary outcome for the TZD arm was the composite of myocardial infa rct ion , stroke or cardiovascular death , and for the vitamin D arm it was cancer or all-cause death . All r and omised participants were included in the primary analysis . From the study design , 16,000 people were to be followed for approximately 5.5 years . However , the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data . In the TZD arm , the cardiovascular outcome occurred in five participants ( 0.9 % ) in the placebo groups and three participants ( 0.4 % ) in the TZD groups ( two allocated to pioglitazone , one to rosiglitazone ) . In the vitamin D arm , the primary outcome occurred in three participants ( 0.5 % ) in the placebo group and in two participants ( 0.3 % ) receiving vitamin D. Adverse events were comparable in all groups . Uncertainty persists regarding the clinical ly relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial . Clinical Trials.gov NCT00879970 The study was funded by GlaxoSmithKline", "BACKGROUND Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter", "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", "Abstract Osteoporosis and related fragility fractures represent a serious and global public health problem . To evaluate whether the modified eighth section of Eight-section Brocade ( MESE ) exercise could improve the symptom and indexes associated with osteoporosis in postmenopausal women . Guangzhou and Liuzhou hospital of traditional Chinese medicine in China . Women ( n = 198 ) aged 50 to 75 years were r and omized into Control , Ca , MESE , and MESE + Ca . Subjects in Ca and MESE groups were separately asked to consume thrice daily Calcium Carbonate Chewable D3 tablet and to perform thrice daily MESE exercise by 7 repetitions per time for 12 months . Subjects in MESE + Ca group performed such the combined treatment project for 12 months . Body height and Hospital for Special Surgery ( HSS ) scores of both knees , chronic back pain visual analogue scale scores ( VAS ) , bone mineral density ( BMD ) at L2 to L4 and the left femoral neck , 3-feet Up and Go Test ( 3′ ) and one-leg Stance ( OLS ) . In our study , the improvement in chronic back pain of the patients in Ca , MESE , and MESE + Ca group was better than that in control group . There was 1.9 % and 1.7 % , 2.3 % , and 2.1 % net profit in left femoral neck and lumbar BMD after the treatment for 12 months in MESE and MESE + Ca groups . For the balance capacity , the subjects in MESE and MESE + Ca groups secured much better performance than those in Ca and control group after the treatment for 12 months ( P treatment of MESE exercise is the most effective for the improvement of the symptom and indexes in postmenopausal women . Importantly , the low attrition and the high exercise compliance indicate that MESE exercise is safe , feasible , and well tolerated by postmenopausal women", "In a double-blind trial , 327 patients ( 57 men ) over 65 ( mean age 79.5 ) years received all possible combinations of calcium carbonate 3 g , vitamin D3 1000 iu , meth and ienone 2.5 mg and /or placebos daily for 9 months . The higher incidence of bone fractures in the placebo group was not significant . Serum calcium , phosphorus , creatinine , aspartate aminotransferase and alkaline phosphatase were followed : the greatest changes occurred with meth and ienone , which thus reduced osteoporotic activity and increased the muscular mass most effectively ; calcium carbonate had the poorest effect . Surprisingly , coronary mortality was higher among those taking all three active substances . With two treatments the increase was not significant , but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments , a significant increase in coronary deaths was seen , most significant ( P less than 0.001 ) in those receiving vitamin D3 and meth and ienone", "CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867", "Background The significance of serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations for hip fracture risk of the elderly is still uncertain . Difficulties reaching both frail and healthy elderly people in r and omized controlled trials or large cohort studies may in part explain discordant findings . We determined hazard ratios for hip fractures of elderly men and women related to serum 25(OH)D , including both the frail and the healthy segment of the elderly population . Methods The AGES-Reykjavik Study is a prospect i ve study of 5764 men and women , age 66–96 years , based on a representative sample of the population of Reykjavik , Icel and . Participation was 71.8 % . Hazard ratios of incident hip fractures and baseline bone mineral density were determined according to serum concentrations of 25(OH)D at baseline . Results Mean follow-up was 5.4 years . Compared with referent values ( 50–75 nmol/L ) , hazard ratios for hip fractures were 2.24 ( 95 % CI 1.63 , 3.09 ) for serum 25(OH)D hazard ratios were 2.61 ( 95 % CI 1.47 , 4.64 ) in men and 1.93 ( 95 % CI 1.31 , 2.84 ) in women . Values significantly lower bone mineral density of femoral neck compared with referent , z-scores -0.14 ( 95 % CI −0.27 , −0.00 ) in men and −0.11 ( 95 % CI −0.22 , −0.01 ) in women . Conclusions Our results lend support to the overarching importance of maintaining serum 25(OH)D above 30 nmol/L for bone health of elderly people while potential benefits of having much higher levels could not be detected", "The importance of vitamin D for bone health is well established , but few data exist on the relation between plasma levels of 25-hydroxyvitamin D and risk of fracture . The authors examined this association within the EPIC-Oxford ( European Prospect i ve Investigation into Cancer and Nutrition-Oxford cohort ) study of men and women in the United Kingdom ( 1993 - 1999 ) . Five years after recruitment , participants completed a follow-up question naire where fracture incidence was self-reported . Plasma 25-hydroxyvitamin D concentration was measured in 730 incident fracture cases and 1,445 matched controls . There was a clear association between plasma 25-hydroxyvitamin D concentration and month of blood draw , the highest values being during the summer months . Among women , there were significant relations between 25-hydroxyvitamin D levels and age , body mass index , marital status , use of hormone therapy , physical activity , diet group , dietary intake of vitamin D , and alcohol . Similar relations were seen among men , although often they were nonsignificant because of smaller numbers . There was no evidence of an association between plasma 25-hydroxyvitamin D and fracture risk for men or women ; the relative risks associated with a doubling of plasma 25-hydroxyvitamin D were 1.15 ( 95 % confidence interval : 0.82 , 1.61 ) and 0.95 ( 95 % confidence interval : 0.80 , 1.13 ) , respectively . These results were not affected by adjustment for potential confounders and were consistent across a number of subgroups", "BACKGROUND The 2009 KDIGO ( Kidney Disease : Improving Global Outcomes ) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 ( 25[OH]D ) levels patients treated with maintenance hemodialysis , but does not provide a specific treatment protocol . STUDY DESIGN 2-center , double-blind , r and omized , 13-week , controlled trial followed by a 26-week open-label study . SETTING & PARTICIPANTS 55 adult maintenance hemodialysis patients with 25(OH)D levels INTERVENTION Cholecalciferol , 25,000IU , per week orally versus placebo for 13 weeks , then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI ( National Kidney Foundation-Kidney Disease Outcomes Quality Initiative ) guidelines . OUTCOMES Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks . Secondary outcomes included the percentage of patients with normal calcium , phosphorus , and intact parathyroid hormone ( iPTH ) blood levels . Safety measures included incidence of hypercalcemia and hypervitaminosis D. MEASUREMENTS Blood calcium and phosphate were measured weekly ; iPTH , 25(OH)D , 1,25-dihydroxyvitamin D3 ( 1,25[OH]2D ) , and bone turnover markers , trimonthly ; fetuin A and fibroblast growth factor 23 ( FGF-23 ) serum levels and aortic calcification scores were determined at weeks 0 and 39 . RESULTS The primary end point significantly increased in the treatment group compared with the placebo group ( 61.5 % vs 7.4 % ; P well as 1,25(OH)2D levels ( 22.5 [ IQR , 15 - 26 ] vs 11 [ IQR , 10 - 15]pg/mL ; P proportion of patients achieving the target calcium level ( 76.9 % vs 48.2 % ; P=0.03 ) . Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups . The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group . LIMITATIONS Small size of the study population . CONCLUSIONS Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective , safe , inexpensive , and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients . Further evaluation of clinical end points is suggested", "Controversy exists in the literature regarding the efficacy of bone health-related nutrients , especially calcium and vitamin D , in preventing fractures . The aim of our present study was to determine the effect of multivitamin and mineral supplementation on fracture incidence among 3,318 participants from a nutritional intervention trial in Linxian , China . A total of 1,461 men and 1,857 women were enrolled and r and omized to daily supplementation with 26 vitamins and minerals tablet or placebo pills for 6 years , followed by a 16-year post-interventional follow-up . The date s , sites , and causes of the fractures were collected retrospectively via a st and ardized question naire . Cox proportional hazard model was used to estimate hazard ratios and 95 % confidence intervals of fracture incidence in the intervention versus the placebo group . A total of 221 fractures ( 57 in men and 164 in women ) occurred during the entire study period of 21 years and 9 months . In men , the supplement reduced the risk of fracture by 63 % during the trial period , and this protective effect was sustained and statistically significant when analysis included both the trial period and 5- or 10-year post-intervention follow-up ( years 0–11 , P = 0.04 ; years 0–16 , P = 0.02 , respectively ) . The protection against fracture was not apparent > 10 years after cessation of the intervention . In women , no significant effect of supplementation on fracture incidence was seen in any of the study periods . These results demonstrate that a 6-year multivitamin and mineral intervention was associated with significant reduction of fracture risk and fracture-related hospitalization in men , but not in women", "Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33", "Background There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients . The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels . Methods In this r and omized controlled study , patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario , Canada . Participants were r and omized to one of three loading dose groups : placebo ; 50,000 IU vitamin D2 ; or 100,000 IU D2 . Following a placebo/loading dose , all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days . Serum 25-hydroxy vitamin D ( 25-OHD ) was measured at baseline , discharge from acute care ( approximately 4-weeks ) , and 3-months . Results Sixty-five patients were enrolled in the study ( 44 % male ) . An immediate rise in 25-OHD occurred in the 100,000 group , however there were no significant differences in 25-OHD between the placebo , 50,000 and 100,000 loading dose groups after 4-weeks ( 69.3 , 84.5 , 75.6 nmol/L , p = 0.15 ) and 3-months ( 86.7 , 84.2 , 73.3 nmol/L , p = 0.09 ) , respectively . At the end of the study , approximately 75 % of the placebo and 50,000 groups had reached the target therapeutic range ( 75 nmol/L ) , and 44 % of the 100,000 group . Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture , our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2 . At the end of the study , all three groups were equally effective in attaining improvement in 25-OHD levels . Given that a daily dose of 1,000 IU vitamin D3 ( with or without a loading dose ) result ed in at least 25 % of patients having suboptimal vitamin D status , patients with acute hip fracture may benefit from a higher daily dose of vitamin D.Trial registration Clinical Trials #", "Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry", "Background Improving vitamin D ( 25-OHD ) status may be an important modifiable factor that could reduce disability severity , fall-rates and mortality associated after hip fracture surgery . Providing a loading-dose post-surgery may overcome limitations in adherence to daily supplementation . Method In this r and omized , double-blind , placebo-controlled trial , 218 adults , aged 65-years or older , requiring hip fracture surgery were assigned to receive a single loading-dose of cholecalciferol ( 250,000 IU vitamin-D3 , the REVITAHIP - Replenishment of Vitamin D in Hip Fracture strategy ) or placebo , both receiving daily vitamin-D(800 IU ) and calcium ( 500 mg ) for 26-weeks . Outcome measures were 2.4 m gait-velocity , falls , fractures , death ( Week-4 ) , 25-OHD levels , quality -of-life measure ( EuroQoL ) and mortality at weeks-2 , 4 and 26 . Results Mean age of 218 participants was 83.9(7.2 ) years and 77.1 % were women . Baseline mean 25-OHD was 52.7(23.5)nmol/L , with higher levels at Week-2 ( 73 vs 66 nmol/L ; p = .019 ) and Week-4 ( 83 vs 75 nmol/L ; p = .030 ) in the Active-group , but not at Week-26 . At week-4 , there were no differences in 2.4 m gait-velocity ( 0.42 m/s vs 0.39 m/s , p = .490 ) , fractures ( 2.7 % vs 2.8 % , p = .964 ) but Active participants reported less falls ( 6.3 % vs 21.1 % , χ2 = 4.327 ; p = 0.024 ) , with no significant reduction in deaths at week-4 ( 1 vs 3 , p = 0.295 ) , higher percentage reporting ‘ no pain or discomfort ’ ( 96.4 % vs 88.8 % , p = 0.037 ) , and trended for higher EuroQoL-scores ( p = 0.092 ) at week-26 . One case of hypercalcemia at week-2 normalised by week-4 . Conclusion Among older people after hip fracture surgery , the REVITAHIP strategy is a safe and low cost method of improving vitamin-D levels , reducing falls and pain levels . Trial registration The protocol for this study is registered with the Australian New Zeal and Clinical Trials Registry ANZCTRN ACTRN12610000392066 ( Date of registration : 14/05/2010 )", "UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation", "Importance Evidence suggests that low vitamin D status may increase the risk of cancer . Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women . Design , Setting , and Participants A 4-year , double-blind , placebo-controlled , population -based r and omized clinical trial in 31 rural counties ( June 24 , 2009 , to August 26 , 2015—the final date of follow-up ) . A total of 2303 healthy postmenopausal women 55 years or older were r and omized , 1156 to the treatment group and 1147 to the placebo group . Duration of treatment was 4 years . Interventions The treatment group ( vitamin D3 + calcium group ) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium ; the placebo group received identical placebos . Main Outcomes and Measures The primary outcome was the incidence of all-type cancer ( excluding nonmelanoma skin cancers ) , which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling . Results Among 2303 r and omized women ( mean age , 65.2 years [ SD , 7.0 ] ; mean baseline serum 25-hydroxyvitamin D level , 32.8 ng/mL [ SD , 10.5 ] ) , 2064 ( 90 % ) completed the study . At year 1 , serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group . A new diagnosis of cancer was confirmed in 109 participants , 45 ( 3.89 % ) in the vitamin D3 + calcium group and 64 ( 5.58 % ) in the placebo group ( difference , 1.69 % [ 95 % CI , −0.06 % to 3.46 % ] ; P = .06 ) . Kaplan-Meier incidence over 4 years was 0.042 ( 95 % CI , 0.032 to 0.056 ) in the vitamin D3 + calcium group and 0.060 ( 95 % CI , 0.048 to 0.076 ) in the placebo group ; P = .06 . In unadjusted Cox proportional hazards regression , the hazard ratio was 0.70 ( 95 % CI , 0.47 to 1.02 ) . Adverse events potentially related to the study included renal calculi ( 16 participants in the vitamin D3 + calcium group and 10 in the placebo group ) , and elevated serum calcium levels ( 6 in the vitamin D3 + calcium group and 2 in the placebo group ) . Conclusions and Relevance Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL , supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years . Further research is necessary to assess the possible role of vitamin D in cancer prevention . Trial Registration clinical trials.gov Identifier :", "BACKGROUND Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture", "Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures . A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites , bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a r and omized , double-blind , placebo-controlled trial . Bone mineral density ( BMD ) was measured by dual x-ray absorptiometry and bone structure by radiographs . Calcium biochemistry and bone turnover markers were measured in blood and urine . The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr . Baseline median calcium intake was 546 mg/day , and median serum 25OH vitamin D3 was 59 nmol/L. On placebo , loss of BMD at total hip was 2 % and femoral medulla expansion was 3 % over 4 yr . Calcium reduced bone loss , secondary hyperparathyroidism , and bone turnover . 25OH vitamin D3 was intermediate between placebo and calcium . Fracture rates and drop-out rates were similar among groups , and there were no serious adverse events with either supplement . A calcium supplement of 750 mg/day prevents loss of BMD , reduces femoral medullary expansion , secondary hyperparathyroidism , and high bone turnover . A supplement of 15 microg/day 25OH vitamin D3 is less effective , and because its effects are seen only at low calcium intakes , suggests that its beneficial effect is to reverse calcium insufficiency", "Background and aims : Insufficient vitamin D status , commonly found in older people , has been associated with muscle weakness which , in old age , impairs mobility and is a risk factor for falling . In a r and omized , double-blind placebo-controlled trial , we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility , compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients . Methods : Seventy female geriatric patients > 65 years of age with serum 25-hydroxyvitamin D3 ( 25OHD ) concentrations between 20 and 50 nmol/L , visiting an outpatient geriatric department , were included . Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day ( D/Cal group ) or a placebo + calcium 500 mg/day ( Plac/Cal group ) for 6 months . At baseline and 6 months , muscle strength , power and functional mobility were tested . Results : At baseline , 25OHD was significantly ( p with knee extension strength ( r=0.42 ) , h and grip strength ( r=0.28 ) , leg extension power ( r=0.34 ) , Timed Get Up and Go ( r=−0.31 ) and Modified Cooper test ( r=0.44 ) . At 6 months , a significant difference in 25OHD ( 77.2 vs 41.6 nmol/L , p and 1,25OHD was found between the two groups . Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups . Conclusions : Daily 400IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) . Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858", "Daily vitamin D in addition to calcium supplementation reduces falls and fractures in older women . However , poor adherence to therapy is a common clinical problem . To examine the effects of supervised oral 3-monthly vitamin D therapy on falls , muscle strength , and mobility , we conducted a 9-month r and omized , double-blind , placebo-controlled trial in 686 community-dwelling ambulant women aged over 70 years . Participants received either oral cholecalciferol 150,000 IU every 3 months ( n = 353 ) or an identical placebo ( n = 333 ) . All participants were advised to increase dietary calcium intake . Falls data were collected 3-monthly . At baseline , 3 , 6 , and 9 months , muscle strength was measured by a h and held dynamometer and mobility by the Timed Up and Go ( TUG ) test . Serum 25 hydroxyvitamin D ( 25OHD ) was measured in a subgroup of 40 subjects . Mean age at baseline was 76.7 ± 4.1 years . The average serum 25OHD value at baseline was 65.8 ± 22.7 nmol/L. By 3 , 6 , and 9 months after supplementation , 25OHD levels of the vitamin D group were approximately 15 nmol/L higher than the placebo group . Calcium intake did not change significantly between baseline ( 864 ± 412 mg/day ) and 9 months ( 855 ± 357 mg/day ) . Faller rates in the two groups did not differ : vitamin D group , 102 of 353 ( 29 % ) ; placebo group , 89 of 333 ( 27 % ) . At 9 months , compared to placebo or baseline , muscle strength , and TUG were not altered by vitamin D. In conclusion , oral cholecalciferol 150,000 IU therapy administered 3-monthly had neither beneficial nor adverse effects on falls or physical function . These data together with previous findings confirm that intermittent large doses of vitamin D are ineffective or have a deleterious effect on falls . Thus despite adherence issues with daily vitamin D replacement , an intermittent , high-dose vitamin D regimen can not be supported as a strategy to reduce falls and fractures", "OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group . Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation", "The effects of vitamin D and parathyroid hormone ( PTH ) levels on incident fracture remain uncertain . To test the hypothesis that increasing serum 25-hydroxyvitamin D [ 25(OH)D ] and decreasing PTH levels are associated with decreased risk of hip and any nonspine fracture , we conducted a prospect i ve cohort study among 2614 community-dwelling white and black participants , aged ≥70 years , from the Health , Aging and Body Composition ( Health ABC ) Study . Serum and plasma sample s were drawn at year 2 , which formed the baseline for this analysis . Serum 25(OH)D and intact PTH ( 1 - 84 ) were measured using radioimmunoassay with DiaSorin reagents and EDTA plasma with a two-site immunoradiometric assay kit , respectively . Incident fractures ( hip and any nonspine ) were assessed after year 2 , every 6 months , by self-report and vali date d by radiology reports . The median ( interquartile range ) follow-up times for hip and any nonspine fractures were 6.4 ( 6.1 - 6.5 ) and 6.4 ( 5.5 - 6.5 ) years , respectively . Cox proportional hazards regression was used to estimate the hazard ratios ( HR ) with 95 % confidence intervals ( CI ) for fracture . There were 84 hip and 247 nonspine fractures that occurred over the follow-up period . The multivariable adjusted HRs ( 95 % CIs ) of hip fracture for participants in the lowest ( ≤17.78 ng/mL ) , second ( 17.79 to 24.36 ng/mL ) , and third quartiles ( 24.37 to 31.94 ng/mL ) of 25(OH)D were 1.92 ( 0.97 to 3.83 ) , 0.75 ( 0.32 to 1.72 ) and 1.86 ( 1.00 to 3.45 ) , respectively , compared with participants in the highest 25(OH)D quartile ( > 31.94 ng/mL ) ( p trend = 0.217 ) . Additional adjustment for IL-6 ( p = 0.107 ) , PTH ( p = 0.124 ) , and hip areal bone mineral density ( p = 0.137 ) attenuated HRs of hip fracture in the lowest quartile by 16.3 % , 17.4 % , and 26.1 % , respectively . There was no evidence of an association between 25(OH)D and any nonspine fractures , or between PTH and hip or any nonspine fractures . We found limited evidence to support an association between calciotropic hormones and hip and nonspine fractures in older men and women", "BACKGROUND Vitamin D , specifically serum 25(OH)D has been associated with mortality , cancer and multiple other health endpoints in observational studies , but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population -wide supplementation . We have therefore launched the D-Health Trial , a r and omized trial of vitamin D supplementation for prevention of mortality and cancer . Here we report the methods and describe the trial cohort . METHODS The D-Health Trial is a r and omized placebo-controlled trial , with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers . Participants aged 65 - 84years were recruited from the general population of Australia . The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo . The primary outcome is all-cause mortality . Secondary outcomes are total cancer incidence and colorectal cancer incidence . RESULTS We recruited 21,315 participants to the trial between February 2014 and May 2015 . The participants in the two arms of the trial were well-balanced at baseline . Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health , to be current smokers or to have diabetes than the Australian population . However , the proportion overweight or with health conditions such as arthritis and angina was similar . CONCLUSIONS Observational data can not be considered sufficient to support interventions delivered at a population level . Large-scale r and omized trials such as the D-Health Trial are needed to inform public health policy and practice", "OBJECTIVES To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient . DESIGN R and omized , placebo-controlled double-blind , trial of 2 years ' duration . SETTING Multicenter study in 60 hostels ( assisted living facilities ) and 89 nursing homes across Australia . PARTICIPANTS Six hundred twenty-five residents ( mean age 83.4 ) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION Vitamin D supplementation ( ergocalciferol , initially 10,000 IU given once weekly and then 1,000 IU daily ) or placebo for 2 years . All subjects received 600 mg of elemental calcium daily as calcium carbonate . MEASUREMENTS Falls and fractures recorded prospect ively in study diaries by care staff . RESULTS The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , the incident rate ratio for falling was 0.73 ( 95 % confidence interval (CI)=0.57 - 0.95 ) . The odds ratio for ever falling was 0.82 ( 95 % CI=0.59 - 1.12 ) and for ever fracturing was 0.69 ( 95 % CI=0.40 - 1.18 ) . An a priori subgroup analysis of subjects who took at least half the prescribed capsules ( n=540 ) , demonstrated an incident rate ratio for falls of 0.63 ( 95 % CI=0.48 - 0.82 ) , an odds ratio ( OR ) for ever falling of 0.70 ( 95 % CI=0.50 - 0.99 ) , and an OR for ever fracturing of 0.68 ( 95 % CI=0.38 - 1.22 ) . CONCLUSION Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient", "Specific receptors for vitamin D have been identified in human muscle tissue . Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls . We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls . In a double-blind r and omized controlled trial , we studied 122 elderly women ( mean age , 85.3 years ; range , 63 - 99 years ) in long-stay geriatric care . Participants received 1200 mg calcium plus 800 IU cholecalciferol ( Cal+D-group ; n = 62 ) or 1200 mg calcium ( Cal-group ; n = 60 ) per day over a 12-week treatment period . The number of falls per person ( 0 , 1 , 2 - 5 , 6 - 7 , > 7 falls ) was compared between the treatment groups . In an intention to treat analysis , a Poisson regression model was used to compare falls after controlling for age , number of falls in a 6-week pretreatment period , and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations . Among fallers in the treatment period , crude excessive fall rate ( treatment - pretreatment falls ) was compared between treatment groups . Change in musculoskeletal function ( summed score of knee flexor and extensor strength , grip strength , and the timed up&go test ) was measured as a secondary outcome . Among subjects in the Cal+D-group , there were significant increases in median serum 25-hydroxyvitamin D ( + 71 % ) and 1,25-dihydroxyvitamin D ( + 8 % ) . Before treatment , mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group . In the 12-week treatment period , mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group . After adjustment , Cal+D-treatment accounted for a 49 % reduction of falls ( 95 % CI , 14 - 71 % ; p crude average number of excessive falls was significantly higher in the Cal-group ( p = 0.045 ) . Musculoskeletal function improved significantly in the Cal+D-group ( p = 0.0094 ) . A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49 % compared with calcium alone . Over this short-term intervention , recurrent fallers seem to benefit most by the treatment . The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function", "Summary In 242 community-dwelling seniors , supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D result ed in a decrease in the number of subjects with first falls of 27 % at month 12 and 39 % at month 20 . Additionally , parameters of muscle function improved significantly . Introduction The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially . R and omized controlled trials using falls as primary outcome are needed . We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men . Methods Our study population consisted of 242 individuals recruited by advertisements and mailing lists ( mean [ ± SD ] age , 77 ± 4 years ) . All serum 25-hydroxyvitamin D ( 25[OH]D ) levels were below 78 nmol/l . Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months , which was followed by a treatment-free but still blinded observation period of 8 months . Falls were documented using diaries . The study took place in Bad Pyrmont , Germany ( latitude 52 ° ) and Graz , Austria ( latitude 46 ° ) . Results Compared to calcium mono , supplementation with calcium plus vitamin D result ed in a significant decrease in the number of subjects with first falls of 27 % at month 12 ( RR = 0.73 ; CI = 0.54–0.96 ) and 39 % at month 20 ( RR = 0.61 ; CI = 0.34–0.76 ) . Concerning secondary endpoints , we observed significant improvements in quadriceps strength of 8 % , a decrease in body sway of 28 % , and a decrease in time needed to perform the TUG test of 11 % . Discussion Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals", "Falls are a serious health problem in the aging population . Because low levels of vitamin D have been associated with increased fall rates , many trials have been performed with vitamin D ; two meta-analyses showed either a small effect or no effect of vitamin D on falls . We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D ( 25OHD ) and data on falls was collected as a secondary outcome . In a 12-month double blind r and omized placebo trial , elderly women , mean age 66 years , were r and omized to one of seven daily oral doses of vitamin D or placebo . The main inclusion criterion for study was a baseline serum 25OHD history of falls was collected at baseline and fall events were collected every 3 months . Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels . There was no decrease in falls on low vitamin D doses 400 , 800 IU , a significant decrease on medium doses 1600 , 2400,3200 IU ( p=0.020 ) and no decrease on high doses 4000 , 4800 IU compared to placebo ( p=0.55 ) . When compared to 12-month serum 25OHD quintiles , the faller rate was 60 % in the lowest quintile , fall rates were 68 % on low dose , 27 % on medium doses and 100 % on higher doses . Fall rates on high doses were increased compared to medium doses ( Odds Ratio 5.6.95 % CI : 2.1 - 14.8 ) . In summary , the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32 - 38ng/ml ( 80 - 95nmol/L ) and faller rates increase as serum 25OHD exceed 40 - 45ng/ml ( 100 - 112.5nmol/L ) . The Tolerable upper limit ( TUL ) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history", "BACKGROUND Vitamin D deficiency is common in older people and may increase risk of falls and fracture . Hospital in patients are at particular risk of falling . Previous studies suggest that vitamin D improves neuromuscular function and reduces falls . OBJECTIVE To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are in patients . DESIGN R and omised , double-blind , controlled study . PARTICIPANTS two hundred and five acute admissions > 65 years to a geriatric medical unit . METHODS Patients were r and omised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg , until discharge or death . RESULTS Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days ( IQR 14.75 - 71.00 ) . In a pre-selected sub-group ( 54/205 participants ) , median admission vitamin D level = 22.00 nmol/l ( IQR 15.00 - 30.50 ) . This did not significantly increase in the treatment versus control group . Median study drug adherence = 88 % , with no significant difference between study groups ( Mann-Whitney : P = 0.711 ) . Although there were fewer fallers in the vitamin D cohort , this did not reach statistical significance ( vitamin D : calcium = 36:45 fallers ; RR 0.82 ( CI 0.59 - 1.16 ) . Neither the mean number of falls ( vitamin D : calcium = 1.040:1.155 ; Mann-Whitney P = 0.435 ) or time to first fall ( Log-rank test P = 0.377 ) differed between groups . CONCLUSIONS In a population of geriatric hospital in patients , vitamin D did not reduce the number of fallers . Routine supplementation can not be recommended to reduce falls in this group", "OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population", "OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13,100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth years ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo . Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-vertebral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved", "Summary In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people , an annual intramuscular injection of ergocalciferol ( 150,000–300,000 IU ) was given to two series of aged subjects : first to 199 ( 45 male ) of 479 subjects ( 110 male ) aged more than 85 years who were living in their own home , and second to 142 ( 29 male ) of 320 ( 58 male ) subjects aged 75–84 and living in a home for aged people . This prospect i ve series was divided into treatment groups according to month of birth . These injections were given annually from September to December in the years 1985–1989 , two to five times to each participant . The fracture rates , laboratory values , vitamin D levels , possible side effects , and mortality were followed until October 1990 . A total of 56 fractures occurred in the 341 vitamin D recipients ( 16.4 % ) and 100 in 458 controls ( 21.8 % ) ( P=0.034 ) . The fracture rate was about the same in both outpatient and municipal home series . Fractures of the upper limb were fewer in the vitamin D recipients , 10/341=2.9 % ( P=0.025 ) , than in the controls , 28/458=6.1 % , during the follow-up . A similar result was obtained in fractures of ribs , 3/341=0.9 % and 12/458=2.6 % , respectively . Fractures of the lower limbs occurred almost as frequently , 31/341=9.1 % , among the vitamin D recipients as among the controls , 49/458=10.7 % . The fracture rate was higher in females ( 22.2 % ) than in males ( 9.5 % ) . The fractures were fewer in the vitamin D recipients only in females . No significant differences were found in total mortality , or due to any group of diseases , between the two treatment groups . No deleterious effects of the vitamin D injections were seen . The authors recommend the supplementation of vitamin D in aged people , at least in northernmost latitudes ( e.g. , as an annual intramuscular injection )", "BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons . Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women", "Antifracture efficacy of high-dose vitamin D ( 800 IU ) and calcium ( 1000 mg ) remains controversial . To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures , we r and omized 3432 women of the population -based Osteoporosis Risk Factor and Prevention ( OSTPRE ) Study cohort ( ages 65 to 71 years ) living in the region of northern Savonia , Finl and ( latitude 62 degrees to 64 degrees N ) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo . The main outcome measure was incident fractures . Fracture data were collected in telephone interviews and vali date d. Data on 3195 women , 1586 in the intervention group and 1609 in the control group , were available for analysis . In adjusted Cox proportional hazards models , the risk of any fracture decreased in the vitamin D and calcium group by 17 % [ adjusted hazard ratio ( aHR ) = 0.83 ; 95 % confidence interval ( CI ) 0.61 - 1.12 ] , and the risk of any nonvertebral fracture decreased by 13 % ( aHR = 0.87 ; 95 % CI 0.63 - 1.19 ) . The risk of distal forearm fractures decreased by 30 % ( aHR = 0.70 ; 95 % CI 0.41 - 1.20 ) , and the risk of any upper extremity fractures decreased by 25 % ( aHR = 0.75 ; 95 % CI 0.49 - 1.16 ) , whereas the risk of lower extremity fractures remained essentially equal ( aHR = 1.02 ; 95 % CI 0.58 - 1.80 ) . None of these effects reached statistical significance . In conclusion , this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65- to 71-year-old general population of postmenopausal women", "Summary The rationale of this study was to determine the effect of high-dose vitamin D3 supplementation on bone mineral density ( BMD ) . Prediabetic males given vitamin D had significantly less reduction in BMD at the femoral neck compared to the controls . The clinical implication s of our findings require further investigation . Introduction Type 2 diabetes mellitus is associated with increased fracture risk , and recent studies show crosstalk between bone and glucose metabolism . Few studies have investigated the effect of vitamin D supplementation on the bone without additional calcium . In the present study , we aim ed to determine whether a high dose of vitamin D3 could improve bone mass density ( BMD ) in prediabetic subjects . Methods The current study was conducted as a secondary research on a previously performed trial , in which 511 subjects with prediabetes were r and omized to vitamin D3 ( 20,000 IU per week ) versus placebo for 5 years . BMD was measured using dual-energy X-ray absorptiometry ( DEXA ) . Results Two hundred and fifty-six subjects were r and omized to vitamin D and 255 to placebo . Mean baseline serum 25-hydroxyvitamin D ( 25(OH)D ) level was 60 nmol/L. Two hundred and two and 214 in the vitamin D and placebo groups , respectively , completed BMD measurements , whereas one in each group was excluded due to use of bisphosphonates . Males given vitamin D had significantly less reduction in BMD at the femoral neck measurement site compared to the controls ( 0.000 versus − 0.010 g/cm2 , p = 0.008 ) . No significant differences between intervention groups were seen at the total hip measurement site , regarding both males and females . Conclusions Vitamin D3 supplementation alone may be beneficial in males with prediabetes , but confirmatory studies are needed", "Context Vitamin D supplementation may help prevent fractures , but the relationship between blood vitamin D concentrations and fracture risk is unclear . Contribution These authors observed an increased risk for hip fracture among women with lower serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations that was independent of measures of frailty , body mass index , physical function , and falls . Caution The authors did not measure bone mineral density ( BMD ) , so they could not determine whether 25(OH ) vitamin D concentrations give different information about fracture risk than that offered by BMD . Implication Low serum 25(OH ) vitamin D concentrations seem to be associated with a higher hip fracture risk . The Editors Vitamin D deficiency is common in older adults , especially during the winter ( 1 ) and in homebound population s ( 2 ) , general medical in patients ( 3 ) , and community-dwelling women admitted to the hospital with acute hip fracture ( 4 ) . A recently published evidence -based report on vitamin D and bone health ( 5 ) found the level of evidence for an association between serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations and fracture risk to be inconsistent ( 5 ) . Since publication of that review , 1 prospect i ve study ( 6 ) reported no relationship between serum 25(OH ) vitamin D concentrations and fractures , whereas another ( 7 ) reported a significantly lower risk for hip fracture with 25(OH ) vitamin D concentrations greater than 60 nmol/L. Vitamin D concentration could be associated with fractures in several ways . It could influence muscle strength and balance , both of which contribute to falls and disability ( 810 ) . The association between 25(OH ) vitamin D concentrations and fracture may also be influenced by renal function , because renal insufficiency has been linked to fracture ( 11 ) and to vitamin D deficiency ( 12 ) . Several interactions between vitamin D and estrogen receptors have been described ( 13 ) ; hormone therapy has been shown to reverse abnormalities in vitamin D metabolism ( 14 ) , and low vitamin D concentrations have also been linked to higher bone turnover ( 15 , 16 ) . Thus , sex-steroid hormones and bone turnover could contribute to the association between 25(OH ) vitamin D concentration and fractures . We conducted a nested casecontrol study within the WHI-OS ( Women 's Health Initiative Observational Study ) among 400 case- patients with adjudicated incident hip fracture and 400 control participants . We tested whether low serum 25(OH ) vitamin D concentrations are associated with a higher risk for hip fractures in community-dwelling women and whether this relationship may be mediated by poor physical functioning , frailty , falls , sex-steroid hormones , renal function , or bone turnover . Methods Study Population Our study population came from the WHI-OS , a prospect i ve cohort study that enrolled 93676 women between 1994 and 1998 at 40 U.S. clinical centers ( age range , 50 to 79 years ) . Study methods are described in detail elsewhere ( 17 ) . In brief , women were eligible if they were postmenopausal , were unlikely to move or die within 3 years , were not enrolled in the WHI clinical trials , and were not currently participating in any other clinical trial . The human subjects review committees from each participating institution approved the study . Follow-up and Outcome Ascertainment We sent women question naires annually to report any hospitalization and other outcomes , including fractures . As of August 2004 , median follow-up duration was 7.1 years ( range , 0.7 to 9.3 years ) . At that time , 3.7 % of participants had withdrawn or were lost to follow-up and 5.3 % had died . We review ed medical records to verify cases of hip fracture , and blinded central adjudicators confirmed the cases ( 18 ) . We excluded patients with pathologic hip fractures . Nested CaseControl Study Design The present study is a casecontrol study nested within the prospect i ve design of WHI-OS . We excluded women who had a history of hip fracture ; were receiving hormone therapy up to 1 year before enrollment ; or were currently receiving and rogens , selective estrogen receptor modulators , antiestrogens , or other osteoporosis treatments ( bisphosphonates , calcitonin , or parathyroid hormone ) . We also excluded women with insufficient serum stored or of unknown ethnicity , leaving 39793 eligible participants . Of these , 404 women had a hip fracture . We r and omly selected 400 of these women to form the incident hip fracture group . For each case-patient , we selected 1 control participant who was within 1 year of the case-patient 's age at screening , was of matching race or ethnicity , and had their blood drawn within 120 days of the case-patient 's blood draw date ; 99 % of case- patients and control participants were matched within 30 days . Baseline Clinical Variables We divided clinical centers into 3 geographic regions on the basis of latitude : northern ( > 40 N ) , middle ( 35 to 40 N ) , and southern ( . We ascertained all covariates at baseline . Clinic interviewers recorded current use of prescription medications by direct inspection of medicine containers . We entered prescription names into the WHI data base and assigned drug codes by using Medispan software ( First Data Bank , San Bruno , California ) . Average amounts of elemental calcium and vitamin D preparations were entered directly from supplement containers . Dietary intakes of calcium and vitamin D were assessed by using a semiquantitative food-frequency question naire ( 19 ) . Total calcium and vitamin D intake was defined as the sum of diet and supplements . We used question naires to ascertain date of birth , race or ethnicity , age at menopause , history of any fracture after age 55 years , smoking , parental history of hip fracture , self-rated health status , and alcohol consumption . We classfied physical activity on the basis of frequency and duration of walking and mild , moderate , and strenuous activities in the previous week . We calculated kilocalories of energy expended in 1 week as the metabolic equivalent ( kcal hours/week per kg ) ( 20 ) . We measured physical function by using the R AND Short Form-36 physical function scale , which comprises 10 items measuring whether health now limits physical function in moderate or vigorous activity ( 2 items ) ; strength to lift , carry , stoop , bend , or stair climb ( 4 items ) ; ability to walk various distances without difficulty ( 3 items ) ; and self-care ( 1 item ) ( 21 ) . The scale is scored from 0 to 100 , with higher scores indicating better physical function . We compared women with a score greater than 90 versus those with a score less than or equal to 90 , a cutoff value corresponding to the median score . We computed a frailty score , which included self-reported muscle weakness and impaired walking speed ( R AND Short Form-36 physical function scale score 75 ) , exhaustion ( R AND Short Form-36 vitality scale score low physical activity ( lowest quartile of physical activity ) , and unintended weight loss between baseline and 3 years of follow-up ( 22 ) . A woman was considered frail if she reported 3 or more of these indicators . Weight was measured on a balance-beam scale with the participant dressed in indoor clothing without shoes . Height was measured by using a wall-mounted stadiometer . Body mass index was calculated as weight ( in kg ) divided by height ( in m2 ) . Laboratory Procedures Laboratory personnel blinded to casecontrol status obtained a 12-hour fasting blood sample at the baseline visit , which was processed and stored at 80C according to strict quality control procedures ( 23 ) . Serum 25(OH ) vitamin D concentrations and sex-steroid hormone levels were measured at the Reproductive Endocrine Research Laboratory at the University of Southern California . 25-Hydroxyvitamin vitamin D was measured by using a radioimmunoassay with DiaSorin reagents ( DiaSorin , Stillwater , Minnesota ) . The sensitivity of the assay was 3.75 nmol/L. The interassay coefficients of variation were 11.7 % , 10.5 % , 8.6 % , and 12.5 % at 14.0 , 56.8 , 82.5 , and 122.5 nmol/L , respectively . Estradiol and testosterone concentrations were quantified by using sensitive and specific radioimmunoassays after organic solvent extraction and celite column partition chromatography ( 2427 ) . The intra- and interassay coefficients of variation were 7.9 % and 8 % to 12 % , respectively , for estradiol and 6 % and 10 % to 12 % , respectively , for testosterone . We calculated bioavailable hormone concentrations by using mass action equations ( 2830 ) . We measured sex hormonebinding globulin by using a solid-phase , 2-site chemiluminescent immunoassay . The intra- and interassay coefficients of variation were 4.1 % to 7.7 % and 5.8 % to 13 % , respectively . Serum cystatin C , a marker of renal function that is independent of age and weight , was measured at Medical Research Laboratories International , Highl and Heights , Kentucky , by using the Dade Behring BN-II nephelometer and Dade Behring reagents ( Dade Behring , Ramsey , Minnesota ) in a particle-enhanced immunonepholometric assay . Serum C-terminal telopeptide of type I collagen and aminoterminal procollagen extensions propeptide were measured by immunoassay ( Synarc , Lyon , France ) . Statistical Analysis We used chi-square and t tests to compare baseline characteristics between case- patients with hip fracture and matched control participants . We assigned 25(OH ) vitamin D concentrations to quartile categories defined on the basis of the distribution in the control participants . To further assess confounding , we compared baseline characteristics across quartiles of 25(OH ) vitamin D concentrations in case- patients and control participants combined . We calculated the P values for trend by using logistic regression and coding the variable of interest as a continuous variable . We assessed the association between serum 25(OH ) vitamin D concentrations and incident hip fracture in conditional logistic regression models that retained the matched casecontrol design . We first examined the unadjusted associations and then adjusted for age ,", "IMPORTANCE Experts debate optimal 25-hydroxyvitamin D ( 25[OH]D ) levels for musculoskeletal health . OBJECTIVE To compare the effects of placebo , low-dose cholecalciferol , and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption , bone mineral density , Timed Up and Go and five sit-to-st and tests , and muscle mass in postmenopausal women with vitamin D insufficiency . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , placebo-controlled clinical trial was conducted at a single center in Madison , Wisconsin , from May 1 , 2010 , through July 31 , 2013 , and the final visit was completed on August 8 , 2014 . A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied . INTERVENTIONS Three arms included daily white and twice monthly yellow placebo ( n=76 ) , daily 800 IU vitamin D3 and twice monthly yellow placebo ( n=75 ) , and daily white placebo and twice monthly 50,000 IU vitamin D3 ( n=79 ) . The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL. MAIN OUTCOMES AND MEASURES Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes , bone mineral density and muscle mass using dual energy x-ray absorptiometry , Timed Up and Go and five sit-to-st and tests , functional status ( Health Assessment Question naire ) , and physical activity ( Physical Activity Scale for the Elderly ) , with Benjamini-Hochberg correction of P values to control for the false discovery rate . RESULTS After baseline absorption was controlled for , calcium absorption increased 1 % ( 10 mg/d ) in the high-dose arm but decreased 2 % in the low-dose arm ( P = .005 vs high-dose arm ) and 1.3 % in the placebo arm ( P = .03 vs high-dose arm ) . We found no between-arm changes in spine , mean total-hip , mean femoral neck , or total-body bone mineral density , trabecular bone score , muscle mass , and Timed Up and Go or five sit-to-st and test scores . Likewise , we found no between-arm differences for numbers of falls , number of fallers , physical activity , or functional status . CONCLUSIONS AND RELEVANCE High-dose cholecalciferol therapy increased calcium absorption , but the effect was small and did not translate into beneficial effects on bone mineral density , muscle function , muscle mass , or falls . We found no data to support experts ' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women . Instead , we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00933244", "RATIONALE Although vitamin D is widely used to promote skeletal health , definitive data on benefits and risks of supplemental vitamin D alone on bone are lacking . Results from large , r and omized controlled trials in the general population are sparse . Data on the effects of supplemental omega-3 fatty acids ( FAs ) on bone are also limited . DESIGN The VITamin D and OmegA-3 TriaL ( VITAL ) is a double-blind , placebo-controlled trial assessing the role of vitamin D3 ( 2000 IU/d ) and omega-3 FA ( 1g/d ) supplements in reducing risks of cancer and cardiovascular disease among U.S. men aged ≥50 and women aged ≥55 . To comprehensively test effects of supplemental vitamin D and /or omega-3 FAs on skeletal health , the VITAL : Effects on Fractures ancillary study is determining the effects of these supplements on incident fractures among 25,875 participants enrolled in the parent trial . Study investigators adjudicate fractures through a detailed review of medical records and radiological images ( hip and femur ) . In a complementary ancillary , VITAL : Effects on Structure and Architecture is determining the effects of supplemental vitamin D and /or omega-3 FAs on bone with detailed phenotyping during in-person visits . Comprehensive assessment s of bone density , turnover , structure/architecture , body composition , and physical performance are being performed at baseline and 2 years post-r and omization . CONCLUSION Results from these studies will clarify the relationship between supplemental vitamin D and /or omega-3 FAs on bone health outcomes , and inform clinical care and public health guidelines on the use of supplemental vitamin D for the primary prevention of fractures in women and men", "R and omized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly . Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known . We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded r and omized controlled trial . Residents from 51 nursing homes were allocated r and omly to receive 5 ml of ordinary cod liver oil ( n = 569 ) or 5 ml of cod liver oil where vitamin D was removed ( n = 575 ) . During the study period of 2 years , fractures and deaths were registered , and the principal analysis was performed on the intention-to-treat basis . Biochemical markers were measured at baseline and after 1 year in a sub sample . Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture . The corresponding figures for all nonvertebral fractures were 76 persons ( control group ) and 69 persons ( vitamin D group ) . There was no difference in the incidence of hip fracture ( p = 0.66 , log-rank test ) , or in the incidence of all nonvertebral fractures ( p = 0.60 , log-rank test ) in the vitamin D group compared with the control group . Compared with the control group , persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter ( p = 0.001 ) . In conclusion , we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people", "BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year", "Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial", "BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo . Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures", "Low 25-hydroxyvitamin D [ 25(OH)D ] levels have been linked to hip fracture in white women . To study the association of 25(OH)D with risk of fracture in multiethnic women , we performed a nested case-control study within the prospect i ve Women 's Health Initiative ( WHI ) Observational Study . Incident fractures were identified in 381 black , 192 Hispanic , 113 Asian , and 46 Native American women over an average of 8.6 years . A r and om sample of 400 white women who fractured was chosen . One control individual was selected per case and matched on age , race/ethnicity , and blood draw date . 25(OH)D , parathyroid hormone , and vitamin D-binding protein ( DBP ) were measured in fasting baseline serum . Conditional logistic regression models were used to calculate the odds ratio ( OR ) and 95 % CI . In multivariable models , higher 25(OH)D levels compared with levels less than 20 ng/mL were associated with a lower risk of fracture in white women ( 20 to higher risk of fracture in black women ( OR = 1.45 , 95 % CI 1.06 - 1.98 ; p trend = 0.043 ) . Higher 25(OH)D ( ≥30.0 ng/mL ) was associated with higher fracture risk in Asian women after adjusting for DBP ( OR = 2.78 , 95 % CI 0.99 - 7.80 ; p trend = 0.04 ) . There was no association between 25(OH)D and fracture in Hispanic or Native American women . Our results suggest divergent associations between 25(OH)D and fracture by race/ethnicity . The optimal level of 25(OH)D for skeletal health may differ in white and black women", "BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475", "Objective To observe the effects of enhanced exercise and combined vitamin D and calcium supplementation on muscular strength and fracture occurrence in postmenopausal women with a high risk of osteoporosis . Methods Totally 614 postmenopausal women at high risk factors of osteoporosis were enrolled in Dongcheng district of Beijing and r and omized into four groups : group A(control group , n=173),group B(regular Tai Chi exercise , n=171),group C(calcium 600 mg/d+VitD3 800 U/d , n=139 ) , and group D[calcium 600 mg/d+25 hydroxyl vitamin D(25OHD ) 0.25 μg/d , n=131].Muscular strength was measured at baseline and one and two years after intervention . Bone turnover markers were measured at baseline and during the two-year follow-up . Falls and fractures were recorded . Results The incidence of 25OHD the left grip strength decreased significantly two years after intervention(t=-3.252,P=0.001)in group A.Right grip strength decreased significantly in group B(t=2.460,P=0.015)while left grip strength improved significantly in group C(t=-2.051,P=0.043)one year after intervention . In group D , muscular strength in both 12-month and 24-month did not change compared with baseline(both P>0.05).Furthermore , serum procollagen type I N-terminal propeptide elevated significantly in group A(t=-2.962,P=0.004),group B(t=-2.888,P=0.005 ) , and group C(t=-2.441,P=0.016),whereas β-C-terminal telopeptide of type I collagen decreased significantly in group B(t=2.285,P=0.024 ) and group D(t=2.596,P=0.011)two years after intervention . Conclusion Enhanced exercise and combined calcium vitamin D supplementation may help sustain muscle strength in postmenopausal women , while calcium and vitamin D supplementation may improve muscular strength within a short period of time", "OBJECTIVE To describe baseline characteristics of the Vitamin D and Type 2 Diabetes ( D2d ) study , the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association ( ADA ) criteria for prediabetes . RESEARCH DESIGN AND METHODS This is a multicenter ( n = 22 sites ) , r and omized , double-blind , placebo-controlled , primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol ( D3 ) compared with placebo on incident diabetes in U.S. adults at risk for diabetes . Eligible participants were at risk for diabetes , defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes : fasting plasma glucose ( FPG ) 100–125 mg/dL , 2-h postload glucose ( 2hPG ) after a 75-g oral glucose load 140–199 mg/dL , and /or a hemoglobin A1c ( HbA1c ) 5.7–6.4 % ( 39–46 mmol/mol ) . RESULTS A total of 2,423 participants ( 45 % of whom were women and 33 % nonwhite ) were r and omized to cholecalciferol or placebo . Mean ( SD ) age was 60 ( 9.9 ) years and BMI 32.1 ( 4.5 ) kg/m2 . Thirty-five percent met all three prediabetes criteria , 49 % met the FPG/HbA1c criteria only , 9.5 % met the 2hPG/FPG criteria only , and 6.3 % met the 2hPG/HbA1c criteria only . Black participants had the highest mean HbA1c and lowest FPG concentration compared with white , Asian , and other races ( P 0.01 ) ; 2hPG concentration did not differ among racial groups . When compared with previous prediabetes cohorts , the D2d cohort had lower mean 2hPG concentration but similar HbA1c and FPG concentrations . CONCLUSIONS D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria", "BACKGROUND Epidemiologic and pre clinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia . To further study the chemopreventive potential of these nutrients , we conducted a r and omized , double-blind , placebo-controlled trial of supplementation with vitamin D , calcium , or both for the prevention of colorectal adenomas . METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy . We r and omly assigned 2259 participants to receive daily vitamin D3 ( 1000 IU ) , calcium as carbonate ( 1200 mg ) , both , or neither in a partial 2 × 2 factorial design . Women could elect to receive calcium plus r and om assignment to vitamin D or placebo . Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations , according to the endoscopist 's recommendation . The primary end point was adenomas diagnosed in the interval from r and omization through the anticipated surveillance colonoscopy . RESULTS Participants who were r and omly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter , relative to participants given placebo . Overall , 43 % of participants had one or more adenomas diagnosed during follow-up . The adjusted risk ratios for recurrent adenomas were 0.99 ( 95 % confidence interval [ CI ] , 0.89 to 1.09 ) with vitamin D versus no vitamin D , 0.95 ( 95 % CI , 0.85 to 1.06 ) with calcium versus no calcium , and 0.93 ( 95 % CI , 0.80 to 1.08 ) with both agents versus neither agent . The findings for advanced adenomas were similar . There were few serious adverse events . CONCLUSIONS Daily supplementation with vitamin D3 ( 1000 IU ) , calcium ( 1200 mg ) , or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00153816 . )", "Background It is hypothesized that in individuals without clinical cardiovascular disease ( CVD ) , but at increased CVD risk , a 50 % to 60 % reduction in CVD risk could be achieved using fixed dose combination ( FDC ) therapy ( usually comprised of multiple blood‐pressure agents and a statin [ with or without aspirin ] ) in a single “ polypill ” . However , the impact of a polypill in preventing clinical CV events has not been evaluated in a large r and omized controlled trial . Methods TIPS‐3 is a 2x2x2 factorial r and omized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population . This study aims to determine whether the Polycap ( comprised of atenolol , ramipril , hydrochlorothiazide , and a statin ) reduces CV events in persons without a history of CVD , but who are at least at intermediate CVD risk . Additional interventions in the factorial design of the study will compare the effect of ( 1 ) aspirin versus placebo on CV events ( and cancer ) , ( 2 ) vitamin D versus placebo on the risk of fractures , and ( 3 ) the combined effect of aspirin and the Polycap on CV events . Results The study has r and omized 5713 participants across 9 countries . Mean age of the study population is 63.9 years , and 53 % are female . Mean INTERHEART risk score is 16.8 , which is consistent with a study population at intermediate CVD risk . Conclusion Results of the TIP‐3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD", "IMPORTANCE While vitamin D supplementation and exercise are recommended for prevention of falls for older people , results regarding these 2 factors are contradictory . OBJECTIVE To determine the effectiveness of targeted exercise training and vitamin D supplementation in reducing falls and injurious falls among older women . DESIGN , SETTING , AND PARTICIPANTS A 2-year r and omized , double-blind , placebo-controlled vitamin D and open exercise trial conducted between April 2010 and March 2013 in Tampere , Finl and . Participants were 409 home-dwelling women 70 to 80 years old . The main inclusion criteria were at least 1 fall during the previous year , no use of vitamin D supplements , and no contraindication to exercise . INTERVENTIONS Four study groups , including placebo without exercise , vitamin D ( 800 IU/d ) without exercise , placebo and exercise , and vitamin D ( 800 IU/d ) and exercise . MAIN OUTCOMES AND MEASURES The primary outcome was monthly reported falls . Injurious falls and the number of fallers and injured fallers were reported as secondary outcomes . In addition , bone density , physical functioning ( muscle strength , balance , and mobility ) , and vitamin D metabolism were assessed . RESULTS Intent-to-treat analyses showed that neither vitamin D nor exercise reduced falls . Fall rates per 100 person-years were 118.2 , 132.1 , 120.7 , and 113.1 in the placebo without exercise , vitamin D without exercise , placebo and exercise , and vitamin D and exercise study groups , respectively ; however , injurious fall rates were 13.2 , 12.9 , 6.5 , and 5.0 , respectively . Hazard ratios for injured fallers were significantly lower among exercisers with vitamin D ( 0.38 ; 95 % CI , 0.17 - 0.83 ) and without vitamin D ( 0.47 ; 95 % CI , 0.23 - 0.99 ) . Vitamin D maintained femoral neck bone mineral density and increased tibial trabecular density slightly . However , only exercise improved muscle strength and balance . Vitamin D did not enhance exercise effects on physical functioning . CONCLUSIONS AND RELEVANCE The rate of injurious falls and injured fallers more than halved with strength and balance training in home-dwelling older women , while neither exercise nor vitamin D affected the rate of falls . Exercise improved physical functioning . Future research is needed to determine the role of vitamin D in the enhancement of strength , balance , and mobility . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00986466", "Few year-long vitamin D supplementation trials exist that match seasonal changes . The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density ( BMD ) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotl and . White women aged 60 to 70 years ( n = 305 ) were r and omized to one of two doses of vitamin D or placebo . All participants started simultaneously in January/February 2009 , attending visits at bimonthly intervals with 265 ( 87 % ) women attending the final visit and an additional visit 1 month after treatment cessation . BMD ( Lunar iDXA ) and 1,25-dihydroxyvitamin D[1,25(OH)2 D ] , N-terminal propeptide of type 1 collagen [ P1NP ] , C-terminal telopeptide of type I collagen [ CTX ] , and fibroblast growth factor-23 [ FGF23 ] were measured by immunoassay at the start and end of treatment . Circulating PTH , serum Ca , and total 25-hydroxyvitamin D [ 25(OH)D ] ( latter by t and em mass spectrometry ) were measured at each visit . Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group ( 0.05 % ± 1.46 % ) compared with the 400 IU vitamin D or placebo groups ( 0.57 % ± 1.33 % and 0.60 % ± 1.67 % , respectively ) ( p 0.05 ) . Mean ( ± SD ) baseline 25(OH)D was 33.8 ± 14.6 nmol/L ; comparative 25(OH)D change for the placebo , 400 IU , and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L , + 31.6 ± 19.8 nmol/L , and + 42.6 ± 18.9 nmol/L , respectively . Treatment did not change markers of bone metabolism , except for a small reduction in PTH and an increase in serum calcium ( latter with 1000 IU dose only ) . The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome , nor how much vitamin D is being stored", "BACKGROUND Adults with low concentrations of 25-hydroxyvitamin D ( 25[OH]D ) in blood have an increased risk of falls and fractures , but r and omised trials of vitamin D supplementation have had inconsistent results . We aim ed to assess the effect of high-dose vitamin D supplementation on fractures and falls . METHODS The Vitamin D Assessment ( ViDA ) Study was a r and omised , double-blind , placebo-controlled trial of healthy volunteers aged 50 - 84 years conducted at one centre in Auckl and , New Zeal and . Participants were r and omly assigned to receive either an initial oral dose of 200 000 IU ( 5·0 mg ) colecalciferol ( vitamin D3 ) followed by monthly 100 000 IU ( 2·5 mg ) colecalciferol or equivalent placebo dosing . The prespecified primary outcome was cardiovascular disease and secondary outcomes were respiratory illness and fractures . Here , we report secondary outcome data for fractures and post-hoc outcome data for falls . Cox proportional hazards models were used to estimate hazard ratios ( HRs ) for time to first fracture or time to first fall in individuals allocated vitamin D compared with placebo . The analysis of fractures included all participants who gave consent and was by intention-to-treat ; the analysis of falls included all individuals who returned one or more question naires . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12611000402943 . FINDINGS Between April 5 , 2011 , and Nov 6 , 2012 , 5110 participants were recruited and r and omly assigned either colecalciferol ( n=2558 ) or placebo ( n=2552 ) . Two participants allocated placebo withdrew consent after r and omisation ; thus , a total of 5108 individuals were included in the analysis of fractures . The mean age of participants was 65·9 years ( SD 8·3 ) and 2971 ( 58 % ) were men . The mean concentration of 25(OH)D in blood was 63 nmol/L ( SD 24 ) at baseline , with 1534 ( 30 % ) having 25(OH)D concentrations lower than 50 nmol/L. Follow-up was until July 31 , 2015 , with a mean treatment duration of 3·4 years ( SD 0·4 , range 2·5 - 4·2 ) . During follow-up , 2638 participants reported having a fall , 1312 ( 52 % ) of 2539 in the vitamin D group compared with 1326 ( 53 % ) of 2517 in the placebo group . The HR for falls-adjusted for age , sex , ethnic origin , history of recent fall , physical activity , and baseline 25(OH)D-was 0·99 ( 95 % CI 0·92 - 1·07 ; p=0·82 ) for vitamin D compared with placebo . Non-vertebral fractures were reported in 292 individuals , 156 ( 6 % ) of 2558 in the vitamin D group and 136 ( 5 % ) of 2550 in the placebo group . The adjusted HR for fractures was 1·19 ( 95 % CI 0·94 - 1·50 ; p=0·15 ) for vitamin D compared with placebo . 123 ( 2 % ) people died during the trial , 65 assigned vitamin D and 58 allocated placebo ; the difference between treatment groups was not significant . INTERPRETATION High-dose bolus vitamin D supplementation of 100 000 IU colecalciferol monthly over 2·5 - 4·2 years did not prevent falls or fractures in this healthy , ambulatory , adult population . Further research is needed to ascertain the effects of daily vitamin D dosing , with or without calcium . FUNDING Health Research Council of New Zeal and and Accident Compensation Corporation of New Zeal and" ]

[ "Background / Objectives : Zinc is an essential micronutrient and deficiency can lead to an increased risk for infectious diseases and growth retardation among children under 5 years of age . We aim ed to estimate disease-specific and all-cause mortality attributable to zinc deficiency . Subject/ Methods : We estimated the prevalence of zinc deficiency in Latin America , Africa and Asia , where based on zinc availability in the diet and childhood stunting rates , zinc deficiency is widespread . The relative risks of death among zinc-deficient children for diarrhea , malaria and pneumonia were estimated from r and omized controlled trials . We used the comparative risk assessment methods to calculate deaths and burden of disease ( measured in disability-adjusted life years , DALYs ) from each of these three diseases attributable to zinc deficiency in these regions . Results : Zinc deficiency was responsible for 453 207 deaths ( 4.4 % of childhood deaths ) , and 1.2 % of the burden of disease ( 3.8 % among children between 6 months and 5 years ) in these three regions in 2004 . Of these deaths , 260 502 were in Africa , 182 546 in Asia and 10 159 in Latin America . Zinc deficiency accounted for 14.4 % of diarrhea deaths , 10.4 % of malaria deaths and 6.7 % of pneumonia deaths among children between 6 months and 5 years of age . Conclusions : Zinc deficiency contributes to substantial morbidity and mortality , especially from diarrhea . Zinc supplementation provided as an adjunct treatment for diarrhea may be the best way to target children most at risk of deficiency", "Apparently healthy preschool children ( 46 boys , 52 girls ) aged 27 - 50 mo from low socioeconomic conditions who attended daycare centers in Santiago participated in a 14-mo long double-blind zinc supplementation trial . Unlike most previous studies , no additional inclusion criteria such as short stature or slow growth rate were considered . Subjects were pair matched according to sex and age and r and omly assigned to two experimental groups : the supplemented group , which received 10 mg Zn/d , and the placebo group . Selected anthropometric , clinical , dietary , biochemical , and functional indexes were determined at the beginning of the study and after 6 and 14 mo of intervention . Actual dietary zinc intake was 66 % of the recommended dietary allowance . Height gain after 14 mo was on average 0.5 cm higher in the supplemented group ( P = 0.10 ) . The response , however , was different between sexes . Boys from the supplemented group gained 0.9 cm more than those in the placebo group ( P = 0.045 ) . No effect was seen in girls . Although no significant differences were observed in the rest of the variables studied , trends ( 0.05 midarm muscle area in boys , improved response to tuberculin , and reduced rates of parasite reinfestation were noted . We conclude that in preschool children of low socioeconomic status , zinc is a limiting factor in the expression of growth potential", "The effects of supplementation of the diets of 6- to 12-year-old children in a village near Shiraz in Iran with zinc plus iron or iron alone , together with the indispensable amino acids in the form of egg white protein , vitamins , minerals , and corn oil have been evaluated . Initially 48 of 59 children had zinc concentrations below the minimum found in well-nourished persons . Eight months of supplementation with zinc plus iron ( 20 mg daily of elemental zinc as carbonate and 20 mg ferrous iron as fumarate ) failed to stimulate growth or bone development or to bring about an increase in plasma zinc concentrations . However , supplementation with iron in the above amount was associated with an acceleration of growth in height and weight . The persistence of low concentrations of zinc in plasma and the failure of supplemental zinc to stimulate growth are attributed to the poor availability of both dietary and supplemental zinc result ing from sequestering action of fiber and phytate present in large amounts in the unleavened whole meal bread consumed by villagers . In addition , the results suggest that simultaneous administration of iron and zinc supplements may impair utilization of the metals", "BACKGROUND The Third National Health and Nutrition Examination Survey suggested some Mexican American children are at risk of zinc deficiency . OBJECTIVE We measured the effects of zinc and micronutrients or of micronutrients alone on indexes of cell-mediated immunity and antiinflammatory plasma proteins . DESIGN Subjects ( n = 54 ) aged 6 - 7 y were r and omly assigned and treated in double-blind fashion in equal numbers with 20 mg Zn ( as sulfate ) and micronutrients or with micronutrients alone 5 d/wk for 10 wk . RESULTS Before treatment the mean + /- SD plasma zinc was 14.9 + /- 1.7 micromol/dL and the range was within the reference ; hair zinc was 1.78 + /- 0.52 micromol/g and 41.6 % were serum ferritin was 25.7 + /- 18.6 microg/L and 50.0 % were zinc and micronutrients treatment increased the lymphocyte ratios of CD4(+ ) to CD8(+ ) and of CD4(+)CD45RA(+ ) to CD4(+)CD45RO(+ ) , increased the ex vivo generation of interleukin-2 ( IL-2 ) and interferon-gamma ( IFN-gamma ) , decreased the generation of interleukin-10 ( IL-10 ) , and increased plasma interleukin-1 receptor antagonist ( sIL-1ra ) and soluble tumor necrosis factor receptor 1 ( sTNF-R1 ) . Micronutrients alone increased the ratio of CD4(+ ) to CD8(+ ) but not of CD4(+)CD45RA(+ ) to CD4(+)CD45RO(+ ) , increased IFN-gamma but had no effect on IL-2 or IL-10 , and increased sIL-1ra but not sTNF-R1 . Efficacy of zinc and micronutrients was greater than micronutrients alone for all indexes except the ratio of CD4(+ ) to CD8(+ ) , which was affected similarly . CONCLUSIONS Before treatment , concentrations of hair zinc in 41.6 % of subjects and serum ferritin in 50 % were consistent with the presence of zinc deficiency . The greater efficacy of the zinc and micronutrients treatment compared with micronutrients alone supports this interpretation", "BACKGROUND Multiple studies have shown the benefits of zinc supplementation among young children in high-risk population s. However , the optimal dose and safe upper level of zinc have not been determined . OBJECTIVES The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration , morbidity , and growth of young children ; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status ; and to determine whether any adverse effects are alleviated by providing copper with zinc . DESIGN This r and omized , double-masked , community-based intervention trial was conducted in 631 Ecuadorian children who were 12 - 30 mo old at baseline and who had initial length-for-age z scores Children received 1 of 5 daily supplements for 6 mo : 3 , 7 , or 10 mg Zn as zinc sulfate , 10 mg Zn + 0.5 mg Cu as copper sulfate , or placebo . RESULTS The change in plasma zinc concentration from baseline was positively related to the zinc dose ( P Zinc supplementation , including doses as low as 3 mg/d , reduced the incidence of diarrhea by 21 - 42 % ( P CONCLUSIONS Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population . There were no observed adverse effects of 10 mg Zn/d on indicators of copper or iron status . The current tolerable upper level of zinc recommended by the Institute of Medicine should be reassessed for young children", "BACKGROUND The coexistence of multiple micronutrient deficiencies is a widespread public health problem in many regions of the world . Interactions between zinc deficiency and vitamin A metabolism have been reported but no longitudinal studies have evaluated the effect of iron deficiency on vitamin A. OBJECTIVE The objective of this study was to investigate the effect of supplementation with iron , zinc , or both on vitamin A and its metabolically related proteins retinol binding protein ( RBP ) and transthyretin . DESIGN The study was a longitudinal , double-blind , placebo-controlled trial in which 219 rural Mexican children aged 18 - 36 mo were r and omly assigned to receive 20 mg Zn/d , 20 mg Fe/d , 20 mg Zn/d plus 20 mg Fe/d , or placebo . RESULTS Six months after supplementation , plasma retinol increased in all supplemented groups . Compared with placebo , zinc supplementation was associated with significantly higher plasma retinol and transthyretin but the increase in RBP was not significant . Iron supplementation significantly increased plasma retinol , RBP , and transthyretin . Supplementation with zinc plus iron significantly increased plasma retinol but not RBP or transthyretin . Children deficient in zinc , iron , or vitamin A ( as indicated by nutrient plasma concentration ) at the beginning of the study had a significantly greater increase in retinol than did children with adequate nutrient status . CONCLUSIONS Supplementation with zinc , iron , or both improved indicators of vitamin A status . The results of this study agree with previous observations of a metabolic interaction between zinc and vitamin A and suggest an interaction between iron and vitamin A metabolism", "The effects of a zinc supplement on growth velocity were assessed in a double-blind , pair-matched controlled study in 40 children with low growth percentiles . Participants were low-income Spanish-American children , 2 to 6 yr of age with heights below the 10th percentile and nutritional or biochemical evidence of zinc deficiency . After 1 yr , the mean height velocity of the zinc-supplemented children was slightly , but significantly ( p less than 0.005 ) , greater than that of control children . This effect was primarily due to a greater height achievement of the zinc-supplemented boys . Increases in height-for-age z-scores were also significant for the supplemented males ( p less than 0.001 ) and for the combined sexes ( p less than 0.05 ) . This study indicates the existence of a growth-limiting syndrome of mild zinc deficiency in children", "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", "The effects of consuming zinc-fortified ready-to-eat breakfast cereals were determined in a double-blind controlled study . The 96 healthy young children who participated ( mean age 58 months ) consumed either zinc-fortified cereal , providing 25 % United States Recommended Dietary Allowance per 1 ounce serving ( test children ) or nonzinc-fortified cereals ( controls ) for a 9-month period . The test children were calculated on average to receive an additional 2.57 mg of zinc per day from this fortification program . This increment increased their mean daily zinc intake to a level that approached the Recommended Dietary Allowance ( 10 mg ) of the National Academy of Sciences for children less than 10 years of age . By the end of the period , the test children ( combined sexes ) had a mean increment of plasma zinc that was 6.5 micrograms/dl greater than that of the control children ( P less than 0.02 ) . The test girls had a greater increment ( 28.5 micrograms/g ) in hair zinc content than controls girls ( P less than 0.05 ) . There were no significant differences in other biochemical parameters including plasma copper and serum cholesterol . No significant differences in food intake or growth velocity were associated with the consumption of the zinc-fortified cereal . Multiple sex and time related differences occurred in plasma , hair , urine , and parotid saliva zinc concentrations that were unrelated to the type of cereal consumed", "BACKGROUND Information is needed on the fractional absorption of zinc ( FAZ ) and absorbed zinc ( AZ ) during prolonged exposure to zinc-fortified foods . OBJECTIVE The objective was to measure FAZ and AZ from diets fortified with different amounts of zinc and to determine whether zinc absorption changes over approximately 7 wk . DESIGN Forty-one stunted , moderately anemic children received daily , at breakfast and lunch , 100 g wheat products fortified with 3 mg Fe ( ferrous sulfate ) and 0 ( group Zn-0 ) , 3 ( group Zn-3 ) , or 9 ( group Zn-9 ) mg Zn ( zinc sulfate ) per 100 g flour . FAZ was measured on days 2 - 3 and 51 - 52 ; meal-specific AZs were calculated as the product of FAZ and zinc intake . RESULTS For the breakfast and lunch meals combined , mean total zinc intakes were 2.14 , 4.72 , and 10.04 mg/d in groups Zn-0 , Zn-3 , and Zn-9 , respectively , during the initial absorption studies ; mean ( + /-SD ) FAZ values were 0.341 + /- 0.111 , 0.237 + /- 0.052 , and 0.133 + /- 0.041 , respectively , on days 2 - 3 ( P Mean initial AZ was positively related to zinc intake ( 0.71 + /- 0.18 , 1.11 + /- 0.21 , and 1.34 + /- 0.47 mg/d , respectively ; P AZ from meals containing zinc-fortified wheat products increases in young children relative to the level of fortification and changes only slightly during approximately 7-wk periods of consumption . Although consumption of zinc-fortified foods may reduce FAZ , zinc fortification at the levels studied positively affects total daily zinc absorption , even after nearly 2 mo of exposure to zinc-fortified diets", "OBJECTIVES : To assess the effect of zinc supplementation on growth and body composition among schoolchildren . DESIGN : R and omized , double-blind , placebo-controlled trial . SETTING AND SUBJECTS : 313 rural Zimbabwean schoolchildren ( 144 boys and 169 girls ) , 11–17 y ) . INTERVENTIONS : Supplementation with zinc ( 30 or 50 mg ) or placebo on schooldays for 12 months . Due to drought , a food programme was in operation during the last eight months of the study .VARIABLES : Weight , height , upper arm circumference , triceps skinfold thickness , and weight-for-age , height-for-age , weight-for-height , arm muscle-area-for-age and arm fat-area-for-age Z-scores . RESULTS : Significant effects on weight gain ( 0.51 vs 0.14 kg , P=0.01 ) , weight-for-age Z ( −0.08 vs −0.14 , P=0.01 ) and arm muscle area-for-age Z-score ( 0.10 vs 0.01 , P=0.03 ) were seen over the first three months , whereas no effects were seen over the full 12 months . CONCLUSIONS : Zinc deficiency impairing lean body mass and weight gain was documented . However , the effect of zinc seen over the first three months vanished during the last nine months when the food programme was in operation . Zinc deficiency may have persisted , but another nutrient may have become growth limiting during the last nine months . SPONSORSHIP : Danish International Development Assistance", "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", "In rural Mexico and in many developing countries micronutrient deficiencies , growth stunting , and morbidity from infectious diseases are highly prevalent in young children . We assessed the extent to which growth stunting could be reversed and the number of infectious disease episodes reduced by zinc and /or iron supplementation . In a double-blind , r and omized community trial 219 Mexican preschoolers were supplemented with either 20 mg Zn as zinc methionine , 20 mg Fe as ferrous sulfate , 20 mg Zn + 20 mg Fe , or a placebo . After 12 mo , plasma zinc increased significantly in the two zinc-treated groups , and plasma ferritin was significantly higher in the two iron-treated groups . There was no effect of treatments on growth velocity or body composition . Children in both zinc-supplemented groups had fewer episodes of disease ( zinc alone , 3.9 + /- 0.3 ; zinc+iron , 3.7 + /- 0.4 ; placebo , 4.6 + /- 0.5 ; P diarrhea ( zinc alone , 0.7 + /- 0.1 ; zinc+iron , 0.8 + /- 0.1 ; placebo , 1.1 + /- 0.2 ; P Zinc and zinc+iron supplements reduced morbidity but had no effect on growth or body composition", "OBJECTIVE To assess the impact of zinc supplementation on nutritional and biochemical parameters among children aged 12 to 59 months . METHODS A blinded r and omized clinical trial was carried out with 58 children aged 12 to 59 months included in the Programa Governamental de Combate a Carências Nutricionais ( National Child Nutritional Program ) , which provided them with 2 kg of iron-fortified milk . The supplementation group ( n = 28 ) received 10 mg/day of zinc sulfate for four months , and the control group ( n = 30 ) received placebo . The following parameters were used to assess the nutritional status : weight-for-height and height-for-age expressed as z scores , according to National Center for Health Statistics ( NCHS ) st and ards , biochemical measurements of serum iron and serum zinc , and hemoglobin and hematocrit levels . RESULTS Zinc supplementation did not have a remarkable influence on anthropometric parameters . Baseline serum zinc levels were low in both groups . After supplementation , variations in mean hemoglobin ( p = 0.002 ) , hematocrit ( p = 0.001 ) , serum zinc ( p = 0.023 ) , and serum iron ( p = 0.013 ) levels significantly increased in the zinc supplementation group . CONCLUSION Zinc supplementation improved hemoglobin response and normalized serum zinc concentration . The results show the importance of establishing policies for nutritional care that can tackle zinc deficiency as well", "OBJECTIVE To establish rates of skeletal mineralization in children and adolescents , and to identify factors that influence these rates . DESIGN Three-year observational study . SETTING University hospital . SUBJECTS Ninety white children , aged 6 to 14 years . MEASUREMENTS Bone mineral density of the radius , spine , and hip was measured at baseline and 3 years later . Physical activity was assessed by question naires at 6-month intervals and dietary calcium intake by diet diary 1 day per month for 36 months . Sexual maturation ( Tanner stage ) was determined by an endocrinologist at 6-month intervals , as necessary to classify children as prepubertal , peripubertal , or postpubertal . RESULTS Skeletal mineralization accelerated markedly at puberty in the spine ( 0.077 vs 0.027 gm/cm2 per year , peripubertal vs prepubertal ) and greater trochanter ( 0.050 vs 0.027 gm/cm2 per year ) , less markedly in the femoral neck ( 0.047 vs 0.030 gm/cm2 per year ) , and only slightly in the radius . Nearly one third ( 15 gm ) of the total skeletal mineral in the lumbar spine of adult women ( approximately 52 gm ) was accumulated in the 3 years around the onset of puberty . Increases in height and weight were the strongest correlates of skeletal mineralization : weight changes were more strongly correlated with trabecular bone sites and changes in height with cortical bone sites . Increases in calf muscle area were strongly associated with mineralization , particularly in peripubertal children , and physical activity was associated with more rapid mineralization in prepubertal children . CONCLUSIONS Puberty has varying effects on skeletal mineralization depending on skeletal site ; trabecular bone is apparently more sensitive to changing hormone concentrations . Physical activity and normal growth are also positively associated with skeletal mineralization , also depending on skeletal site and sexual maturation", "OBJECTIVE The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different population s. STUDY DESIGN In a r and omized , placebo-controlled , masked clinical trial , we assigned term Swedish ( n = 101 ) and Honduran ( n = 131 ) infants to 3 groups at 4 months of age : ( 1 ) iron supplements , 1 mg/kg/d , from 4 to 9 months , ( 2 ) placebo , 4 to 6 months and iron , 6 to 9 months , and ( 3 ) placebo , 4 to 9 months . All infants were breast-fed exclusively to 6 months and partially to 9 months . RESULTS From 4 to 6 months , the effect of iron ( group 1 vs 2 + 3 ) was significant and similar in both population s for hemoglobin , ferritin , and zinc protoporphyrin . From 6 to 9 months , the effect ( group 2 vs group 3 ) was significant and similar at both sites for all iron status variables except hemoglobin , for which there was a significant effect only in Honduras . In Honduras , the prevalence of iron deficiency anemia at 9 months was 29 % in the placebo group and 9 % in the supplemented groups . In Sweden , iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months ( Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants . The unexpected hemoglobin response at 4 to 6 months in both population s suggests that regulation of hemoglobin synthesis is immature at this age", "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" ]

[ "A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity", "The effects of two different prevention programmes on : ( 1 ) reported neck , shoulder and back pain , ( 2 ) perceived physical exertion at work and perceived work-related psychosocial factors , were evaluated by question naires after 12 and 18 months . Female nursing aides and assistant nurses ( n = 282 ) working in the home-care services , were r and omly assigned to one of three groups for : ( 1 ) individually design ed physical training programme , ( 2 ) work-place stress management , ( 3 ) control group . Results revealed no significant differences between the three groups . However , improvements in low back pain were registered within both intervention groups for up to 18 months . Perceived physical exertion at work was reduced in the physical training group . Improvements in neck and shoulder pain did not differ within the three groups . Dissatisfaction with work-related , psychosocial factors was generally increased in all groups . As the aetiology of neck , shoulder and back disorders is multifactorial , a combination of the two intervention programmes might be preferable and should be further studied", "CONTEXT Low back pain is a frequent and costly health problem . Prevention of low back pain is important both for the individual patient and from an economic perspective . OBJECTIVE To assess the efficacy of lumbar supports and education in the prevention of low back pain in industry . DESIGN A r and omized controlled trial with a factorial design . SETTING The cargo department of an airline company in the Netherl and s. PARTICIPANTS A total of 312 workers were r and omized , of whom 282 were available for the 6-month follow-up . INTERVENTIONS Subjects were r and omly assigned to 4 groups : ( 1 ) education ( lifting instructions ) and lumbar support , ( 2 ) education , ( 3 ) lumbar support , and ( 4 ) no intervention . Education consisted of 3 group sessions on lifting techniques with a total duration of 5 hours . Lumbar supports were recommended to be used during working hours for 6 months . MAIN OUTCOME MEASURES Low back pain incidence and sick leave because of back pain during the 6-month intervention period . RESULTS Compliance with wearing the lumbar support at least half the time was 43 % . In the 282 subjects for whom data were available , no statistically significant differences in back pain incidence ( 48 [ 36 % ] of 134 with lumbar support vs 51 [ 34 % ] of 148 without , P=.81 ) or in sick leave because of low back pain ( mean , 0.4 days per month with lumbar support vs 0.4 days without , P=.52 ) were found among the intervention groups . In a subgroup of subjects with low back pain at baseline , lumbar supports reduced the number of days with low back pain per month ( median , 1.2 vs 6.5 days per month ; P=.03 ) . CONCLUSIONS Overall , lumbar supports or education did not lead to a reduction in low back pain incidence or sick leave . The results of the subgroup analysis need to be confirmed by future research . Based on our results , the use of education or lumbar supports can not be recommended in the prevention of low back pain in industry", "STUDY DESIGN A systematic review of r and omized and nonr and omized controlled trials . SUMMARY OF BACKGROUND DATA Lumbar supports are used in the treatment of low back pain , but also to prevent the onset ( primary prevention ) or recurrences of a low back pain episode ( secondary prevention ) . OBJECTIVES To assess the effects of lumbar sup-ports for prevention and treatment of nonspecific low back pain . METHODS The Medline , Cinahl , and Current Contents data bases ; the Cochrane Controlled Trials Register up to September 1999 ; and the Embase data base up to September 1998 were all search ed . References of identified trials and systematic review s were review ed and the Science Citation Index used to identify additional trials . Method ologic quality assessment and data extraction were performed by two review ers independently . A quantitative analysis was performed in which the strength of evidence was classified as strong , moderate , limited or conflicting , and no evidence . RESULTS Five r and omized and two nonr and omized preventive trials and six r and omized therapeutic trials were included in the review . Only 4 of the 13 studies were of high quality . There was moderate evidence that lumbar supports are not effective for primary prevention . No evidence was found on the effectiveness of lumbar supports for secondary prevention . The systematic review of therapeutic trials showed that there is limited evidence that lumbar supports are more effective than no treatment , whereas it is still unclear whether lumbar supports are more effective than other interventions for treatment of low back pain . CONCLUSIONS There continues to be a need for high quality r and omized trials on the effectiveness of lumbar supports . One of the most essential issues to tackle in these future trials seems to be the realization of adequate compliance", "This study was funded in part by NIH grant AR36308 The authors thank the employees of the United States Postal Service and the American Postal Workers Union ( APWU ) , Boston Metro Area Local , and Maith and lers Local 301 for their help and cooperation ; therapists from the Department of Rehabilitation Services , Bngham and Women 's Hospital for help in training workers ; and Ms Nancy Tanner for", "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", "This study was design ed to determine the effect of multimodal intervention and the prevention of back injury , and to evaluate the adverse side effects of using a lumbosacral corset in the workplace . Subjects were 90 male warehouse workers r and omly selected from over 800 employees at a grocery distribution center . Subjects were assigned to three groups : true controls , no back school , no brace orthoses ; back school only ; and back school plus wearing a custom molded lumbosacral orthosis . Comparisons of pre-testing and 6-month follow-up posttesting for abdominal strength , cognitive data , work injury incidence and productivity and use of health care services were evaluated . Controls and training-only group showed no changes in strength productivity or lost time . Orthoses and training-group showed no changes in strength productivity or accident rate ; however , they showed substantially less lost time . This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss . It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries", "The personnel at a geriatric hospital were r and omized into two groups . One group was allowed to exercise during working hours to improve back muscle strength , endurance , and coordination . The other group did not participate in the exercise program and received no further advice or information . After 13 months , the training group had increased back muscle strength . One subject had been absent from work 28 days in the training group whereas 12 subjects had been absent 155 days from work because of low back pain in the control group ( P back pain complaints and intensity of back pain in the training group also decreased in a statistically significant way . Every hour spent by the physiotherapist on the training group reduced the work absence among the participants by 1.3 days , result ing in a cost/benefit ratio greater than 10", "To define the cost-effectiveness of a back school program in industry , a controlled longitudinal field study was carried out in a Dutch bus company . The experimental group received a program consisting of information on back care , physical fitness , nutrition , stress , and relaxation . Objective data on absenteeism were collected and compared during a 6-year period for the control and experimental groups . Results showed that a tailor-made back school program reduced absenteeism by at least 5 days per year per employee , therefore being cost-effective to industry . A reduction was not observed in incidence , but in mean length of absenteeism . This effect turned out to be persistent during a 2-year period following the program", "The purpose s of this study were to evaluate the effect of a weekly exercise program on short-term sick leave ( less than 50 days ) attributable to back pain and to determine whether changes in absenteeism were related to changes in cardiovascular fitness . Subjects were r and omly assigned to an exercise group ( n = 58 ) and a control group ( n = 53 ) . Sick leave attributable to back pain was determined in the intervention period of 1 1/2 years and a comparable 1 1/2-year period prior to the study . In the exercise group , the number of episodes of back pain and the number of sick-leave days attributable to back pain in the intervention period decreased by over 50 % . Absenteeism attributable to back pain increased in the control group . The decrease in sick leave in the exercise group was not accompanied by any change in cardiovascular fitness . Suggestions for establishing exercise programs are given", "CONTEXT Despite scientific uncertainties about effectiveness , wearing back belts in the hopes of preventing costly and disabling low back injury in employees is becoming common in the workplace . OBJECTIVE To evaluate the effectiveness of using back belts in reducing back injury cl aims and low back pain . DESIGN AND SETTING Prospect i ve cohort study . From April 1996 through April 1998 , we identified material -h and ling employees in 160 new retail merch and ise stores ( 89 required back belt use ; 71 had voluntary back belt use ) in 30 states ( from New Hampshire to Michigan in the north and from Florida to Texas in the south ) ; data collection ended December 1998 , median follow-up was 6(1/2 ) months . PARTICIPANTS A referred sample of 13,873 material h and ling employees provided 9377 baseline interviews and 6311 ( 67 % ) follow-up interviews ; 206 ( 1.4 % ) refused baseline interview . MAIN OUTCOME MEASURES Incidence rate of material -h and ling back injury workers ' compensation cl aims and 6-month incidence rate of self-reported low back pain . RESULTS Neither frequent back belt use nor a belt-requirement store policy was significantly associated with back injury cl aim rates or self-reported back pain . Rate ratios comparing back injury cl aims of those who reported wearing back belts usually every day and once or twice a week vs those who reported wearing belts never or once or twice a month were 1.22 ( 95 % confidence interval [ CI ] , 0.87 - 1.70 ) and 0.95 ( 95 % CI , 0.56 - 1.59 ) , respectively . The respective odds ratios for low back pain incidence were 0.97 ( 95 % CI , 0.83 - 1.13 ) and 0.92 ( 95 % CI , 0.73 - 1.16 ) . CONCLUSIONS In the largest prospect i ve cohort study of back belt use , adjusted for multiple individual risk factors , neither frequent back belt use nor a store policy that required belt use was associated with reduced incidence of back injury cl aims or low back pain . JAMA . 2000;284:2727 - 2732", "This study evaluated the efficacy of a commercially available weightlifting belt in relation to reduction of lumbar injury incident rate and severity of injuries over an 8-month period . The study used 642 baggage h and lers working for a major airline company as participants . Four treatment groups were r and omly selected : a group receiving the belt only , a group receiving a 1 h training class only , a group receiving both a belt and a 1 h training class , and a control group receiving nothing . Two treatment groups were added which contained participants who discontinued use of the belt prior to the end of an 8-month study period . Results indicated that there were no significant differences for total lumbar injury incident rate , restricted workday case injury incident rate , lost workdays and restricted workdays rate , and worker 's compensation rates . There was , however , a marginal significant difference for lost workday case injury incident rate . Groups with participants who wore the belt for a while then discontinued its use had a higher lost day case injury incident rate than did either the group receiving training only or the control group . Compliance was an overriding factor as the belt question naire response indicated that 58 % of participants in the belt groups discontinued use of the belt before the end of 8 months . Comments made on the survey forms indicated that the belt was too hot . Similarly , comments suggested that the belt rubbed , pinched , and bruised ribs . Based on these results , the weightlifting belt used for this study can not be recommended for use in aid of lifting during daily work activities of baggage h and lers . Results indicate that use of the belts may , in fact , increase the risk of injury when not wearing a belt following a period of wearing a belt . As industries are experimenting with the use of belts , it is recommended that great care be taken in any further evaluation and close attention directed towards injuries which occur when not wearing the belt following a period of wearing the belt ( ie , off-the-job injuries )" ]

[ "OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year", "BACKGROUND Our objective was to test the effect of physicians providing brief health lifestyle counseling to patients with type 2 diabetes mellitus during usual care visits . METHODS We conducted a r and omized controlled trial of a 12-month intervention at 2 large community health centers , enrolling 310 patients with a body mass index ( calculated as weight in kilograms divided by height in meters squared ) of 25 or greater . In the intervention group , self-management goals for nutrition and physical activity were set using a tailored computer program . Goals were then review ed at each clinic visit by physicians . The control group received only printed health education material s. The main outcome measures included change in physical activity and body weight . RESULTS In the intervention group , recommended levels of physical activity increased from 26 % at baseline to 53 % at 12 months ( P < .001 ) compared with controls ( 30 % to 37 % ; P= .27 ) , and 32 % of patients in the intervention group lost 6 or more pounds at 12 months compared with 18.9 % of controls ( odds ratio , 2.2 ; P= .006 ) . CONCLUSION A brief intervention to increase the dialogue between patients and health care providers about behavioral goals can lead to increased physical activity and weight loss", "OBJECTIVE To improve quality and efficiency of care for elderly patients with type 2 diabetes , we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare ( u-healthcare ) service , which is an individualized health management system using advanced medical information technology . RESEARCH DESIGN AND METHODS We conducted a 6-month r and omized , controlled clinical trial involving 144 patients aged > 60 years . Participants were r and omly assigned to receive routine care ( control , n = 48 ) , to the self-monitored blood glucose ( SMBG , n = 47 ) group , or to the u-healthcare group ( n = 49 ) . The primary end point was the proportion of patients achieving A1C without hypoglycemia at 6 months . U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient ’s mobile phone . Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server . Once the data are transferred to the server , an automated system , the CDSS rule engine , generates and sends patient-specific messages by mobile phone . RESULTS After 6 months of follow-up , the mean A1C level was significantly decreased from 7.8 ± 1.3 % to 7.4 ± 1.0 % ( P proportion of patients with A1C was 30.6 % in the u-healthcare group , 23.4 % in the SMBG group ( 23.4 % ) , and 14.0 % in the control group ( P u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients", "PURPOSE The Women to Women Diabetes Project tested the use of telecommunication technology to deliver diabetes education and social support to rural women with diabetes . The aims were to ( 1 ) test the effects of the computer intervention in providing support , information , and education on selected outcomes , and ( 2 ) evaluate the women 's attitudes toward and satisfaction with the intervention and the support provided . METHODS Thirty women were r and omized into computer and noncomputer groups and participated for 10 months . For 5 months , one group participated in a self-help support and educational group via the computer ; the other group continued to use their usual modes of support and communication . Psychosocial well-being scales were administered and attitudes were surveyed . RESULTS Improving health and higher educational levels positively influenced measures of social support and quality of life . Women who were married or who reported greater support had higher scores on the Personal Re source Question naire . The women expressed positive effects of the computer-based support group on their lives . CONCLUSIONS The intervention was enthusiastically accepted , and could be conducted effectively in isolated rural areas", "OBJECTIVE We hypothesized that people with type 2 diabetes in an online diabetes self-management program , compared with usual-care control subjects , would 1 ) demonstrate reduced A1C at 6 and 18 months , 2 ) have fewer symptoms , 3 ) demonstrate increased exercise , and 4 ) have improved self-efficacy and patient activation . In addition , participants r and omized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement . RESEARCH DESIGN AND METHODS A total of 761 participants were r and omized to 1 ) the program , 2 ) the program with e-mail reinforcement , or 3 ) were usual-care control subjects ( no treatment ) . This sample included 110 American Indians/Alaska Natives ( AI/ANs ) . Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups . RESULTS At 6 months , A1C , patient activation , and self-efficacy were improved for program participants compared with usual care control subjects ( P health or behavioral indicators . The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects . The subgroup with initial A1C > 7 % demonstrated stronger improvement in A1C ( P = 0.01 ) . At 18 months , self-efficacy and patient activation were improved for program participants . A1C was not measured . Reinforcement showed no improvement . CONCLUSIONS An online diabetes self-management program is acceptable for people with type 2 diabetes . Although the results were mixed they suggest 1 ) that the program may have beneficial effects in reducing A1C , 2 ) AI/AN population s can be engaged in and benefit from online interventions , and 3 ) our follow-up reinforcement appeared to have no value", "This paper describes the development and evaluation of a computer-aided learning ( CAL ) program . The program was tested in a trial that involved 36 people with diabetes ; 20 received CAL lessons in diabetes management and 16 attended conventional diabetes classes conducted by diabetes educators . When measurements taken before and three months after the education were compared , both groups showed significant improvement in their knowledge ; the blood glucose levels of the CAL group were significantly lower but those of the conventional education group were higher . This means that the CAL program was as effective as conventional education in imparting knowledge but it was more likely to motivate people to control their glucose levels . The CAL program allows diabetes educators to spend less time on education in basic knowledge and to concentrate more on motivational and social factors that are important determinants of patient compliance . It can also benefit people with diabetes whose access to health professionals and /or conventional diabetes education is restricted", "BACKGROUND A prerequisite to translating research findings into practice is information on consistency of implementation , maintenance of results , and generalization of effects . This follow-up report is one of the few experimental studies to provide such information on Internet-based health education . METHODS We present follow-up data 10 months following r and omization on the \" Diabetes Network ( D-Net ) \" Internet-based self-management project , a r and omized trial evaluating the incremental effects of adding ( 1 ) tailored self-management training or ( 2 ) peer support components to a basic Internet-based , information-focused comparison intervention . Participants were 320 adult type 2 diabetes patients from participating primary care offices , mean age 59 ( SD = 9.2 ) , who were relatively novice Internet users . RESULTS All intervention components were consistently implemented by staff , but participant website usage decreased over time . All conditions were significantly improved from baseline on behavioral , psychosocial , and some biological outcomes ; and there were few differences between conditions . Results were robust across on-line coaches , patient characteristics , and participating clinics . CONCLUSIONS The basic D-Net intervention was implemented well and improvements were observed across a variety of patients , interventionists , and clinics . There were , however , difficulties in maintaining usage over time and additions of tailored self-management and peer support components generally did not significantly improve results", "This study evaluated the 12-month follow-up results and costs of a personalized , medical office-based intervention focused on behavioral issues related to dietary self-management . Two hundred and six adults having diabetes attending an internal medicine outpatient clinic visit were r and omized to either Usual Care or to Brief Intervention . The single session intervention involved touchscreen computer-assisted assessment that provided immediate feedback on key barriers to dietary self-management , goal setting and problem-solving counselling . Follow-up components included phone calls and videotape intervention relevant to each participant . Brief Intervention produced significantly greater improvement than Usual Care on multiple measures of change in dietary behaviour ( e.g. , covariate adjusted difference of 2.2 % of calories from fat ; p = 0.023 ) and on serum cholesterol levels ( covariate adjusted difference of 15 mg/dl ; p = 0.002 ) at 12-month follow-up . There were also significant differences favouring intervention on patient satisfaction ( p HbA1c levels . The costs of intervention ( $ 137 per patient ) were modest relative to many commonly used practice", "OBJECTIVE Internet and other interactive technology-based programs offer great potential for practical , effective , and cost-efficient diabetes self-management ( DSM ) programs capable of reaching large numbers of patients . This study evaluated minimal and moderate support versions of an Internet-based diabetes self-management program , compared to an enhanced usual care condition . RESEARCH DESIGN AND METHODS A three-arm practical r and omized trial was conducted to evaluate minimal contact and moderate contact versions of an Internet-based diabetes self-management program , offered in English and Spanish , compared to enhanced usual care . A heterogeneous sample of 463 type 2 patients was r and omized and 82.5 % completed a 4-month follow-up . Primary outcomes were behavior changes in healthy eating , physical activity , and medication taking . Secondary outcomes included hemoglobin A1c , body mass index , lipids , and blood pressure . RESULTS The Internet-based intervention produced significantly greater improvements than the enhanced usual care condition on three of four behavioral outcomes ( effect sizes [ d ] for healthy eating = 0.32 ; fat intake = 0.28 ; physical activity= 0.19 ) in both intent-to-treat and complete-cases analyses . These changes did not translate into differential improvements in biological outcomes during the 4-month study period . Added contact did not further enhance outcomes beyond the minimal contact intervention . CONCLUSIONS The Internet intervention meets several of the RE- AIM criteria for potential public health impact , including reaching a large number of persons , and being practical , feasible , and engaging for participants , but with mixed effectiveness in improving outcomes , and consistent results across different subgroups . Additional research is needed to evaluate longer-term outcomes , enhance effectiveness and cost-effectiveness , and underst and the linkages between intervention processes and outcomes", "Objective : There is a need for practical , efficient and broad-reaching diabetes self-management interventions that can produce changes in lifestyle behaviours such as healthy eating and weight loss . The objective of this study was to evaluate such a computer-assisted intervention . Methods : Type 2 diabetes primary care patients ( n=335 ) from fee-for-service and health maintenance organization setting s were r and omized to social cognitive theory-based tailored self-management ( TSM ) or computer-aided enhanced usual care ( UC ) . Intervention consisted of computer-assisted self-management assessment and feedback , tailored goal - setting , barrier identification , and problem-solving , followed by health counsellor interaction and follow-up calls . Outcomes were changes in dietary behaviours ( fat and fruit/vegetable intake ) , haemoglobin A1c ( HbA1c ) , lipids , weight , quality of life , and depression . Results : TSM patients reduced dietary fat intake and weight significantly more than UC patients at the 2-month follow-up . Among patients having elevated levels of HbA1c , lipids or depression at baseline , there were consistent directional trends favouring intervention , but these differences did not reach significance . The intervention proved feasible and was implemented successfully by a variety of staff . Conclusions : This relatively low-intensity intervention appealed to a large , generally representative sample of patients , was well implemented , and produced improvement in targeted behaviours . Implication s of this practical clinical trial for dissemination are discussed", "AIMS The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide . To improve the quality and efficiency of chronic disease care , we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care ( UCDC ) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension . METHODS We conducted a r and omized , controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre . RESULTS After 12 weeks , there were significant improvements in HbA(1c ) in the intervention group ( 7.6 + /- 0.9 % to 7.1 + /- 0.8 % , P systolic and diastolic blood pressure , as well as improvements in total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels in the intervention group . Furthermore , there was a significant increase in adiponectin levels in the intervention group compared with the control group , although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group . CONCLUSIONS The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension", "OBJECTIVE To evaluate the efficacy of the \" Diabetes Diet Advisor\"(PC-DR vision 1.0 ) \" for type 2 diabetes . METHODS One hundred and fifty type 2 diabetic patients were divided in the 2 groups . The study group included 88 type 2 diabetic patients managed by \" Diabetes Diet Advisor(PC-DR vision 1.0 ) \" ; the control group included 62 cases with a fixed carbohydrate content . All patients were followed up for 8 weeks . RESULTS After 8 weeks dietary therapy , the fasting blood glucose ( FBG ) , cholesterol ( TC ) , triglycerides ( TG ) , HDL-cholesterol ( HDL- C ) and body mass index ( BMI ) in study group were all significantly less than those in the control group ( P FBG and 2hPBG decreased persistently . Twenty-five patients ( 28.41 % ) in study group and 6 patients ( 9.68 % ) in control group reduced their dosage of hypoglycemic agents or stopped drug therapy ( P=0.007 ) . CONCLUSION The software \" Diabetes Diet Advisor ( PC-DR vision 1.0 ) \" is a useful tool of dietary management for patients with type 2 diabetes", "OBJECTIVE There is a well-documented gap between diabetes care guidelines and the services received by patients in most health care setting s. This report presents 12-month follow-up results from a computer-assisted , patient-centered intervention to improve the level of recommended services patients received from a variety of primary care setting s. RESEARCH DESIGN AND METHODS A total of 886 patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program . Physicians were stratified and r and omized to intervention or control conditions and evaluated on two primary outcomes : number of recommended laboratory screenings and recommended patient-centered care activities completed from the National Committee on Quality Assurance/American Diabetes Association Provider Recognition Program ( PRP ) . Secondary outcomes were evaluated using the Problem Areas in Diabetes 2 quality of life scale , lipid and HbA1c levels , and the Patient Health Question naire-9 depression scale . RESULTS The program was well implemented and significantly improved both the number of laboratory assays and patient-centered aspects of diabetes care patients received compared with those in the control condition . There was overall improvement on secondary outcomes of lipids , HbA1c , quality of life , and depression scores ; between-condition differences were not significant . CONCLUSIONS Staff in small , mixed-payer primary care offices can consistently implement a patient-centered intervention to improve PRP measures of quality of diabetes care . Alternative explanations for why these process improvements did not lead to improved outcomes , and suggested directions for future research are discussed", "BACKGROUND Aggressive management of blood glucose reduces future diabetes-related complications , but this is difficult to achieve . METHODS This r and omized , controlled study tested the effect of using a wireless two-way pager-based automated messaging system to improve diabetes control through facilitated self-management . The system sent health-related messages to patients , with automatic forwarding of urgent patient responses to the health care team . RESULTS Participants in both the experimental ( pager ) and the control groups experienced an average hemoglobin A1c decrease of 0.1 - 0.3 % . More patients in the pager group were normotensive , and more felt that their health care was better by the end of the study . A total of 79 % of participants enjoyed using the pager , and 68 % wanted to continue using the system . CONCLUSIONS Utilizing a wireless , automated messaging system in clinical practice is a feasible , low-cost , interactive way to facilitate diabetes self-management , which is acceptable to patients . While providing a convenient way for patients and providers to communicate , this system can support automated recording and ready retrieval of these real-time interactions", "BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant" ]

[ "Objective In this study , the injury incidence and association with type and volume of training in international rowers were described . Design A prospect i ve cohort design was used over a 12-month period . Patients 20 international rowers who were competing as part of the Irish Amateur Rowing Union squad system . Methods The rowers were interviewed monthly , and data were collected regarding their training and competition exposure as well as their injury experience . Results A mean injury rate of 3.67 per 1000 exposure hours was reported with a total of 44 injuries reported in a 12-month period . The mean number of injuries sustained per athlete was 2.2 ( 1.24 ) over the 12-month period . The area where the greatest number of injuries were reported was the lumbar spine ( 31.82 % of total injuries , 95 % CI 20 to 50 ) ( fig 2 ) followed by the knee ( 15.91 % of total injuries , 95 % CI 10 to 30 ) and the cervical spine ( 11.36 % of total injuries , 95 % CI 5 to 24 ) . Half of the injuries ( 22 injuries , 50 % of total reported injuries ) were to the spine ( χ2 = 30.8 , df = 9 , p = 0.0003 ) . Ergometer training load was the most significantly associated with injury risk ( r = 0.68 , p = 0.01 ) . Conclusion International rowers are at higher risk of injury than most non-contact sports and some contact sports . The high risk of lumbar spine injury and the significant association of high volume of ergometer training merit further research to reduce time and competition lost to injury", "OBJECTIVES This study aim ed to identify modifiable mechanisms associated with low back injury in adolescent cricket fast bowlers . DESIGN A prospect i ve study design examined the association between intrinsic risk factors , workload , bowling kinematics , lumbar load and low back injury incidence . METHODS Twenty-five injury free fast bowlers , aged 14 - 19 years , were assessed prior to the start of a cricket season and observed during the season for low back injuries . RESULTS The twelve bowlers who suffered a low back injury displayed ; decreased hip flexion at front foot contact ( 46±6 ° vs 51±6 ° ) , increased pelvis rotation ( 287±11 ° vs 277±11 ° ) increased thorax lateral flexion ( 50±6 ° vs 40±8 ° ) at ball release , and larger peak lumbar flexion ( 10.5±4.9Nmkg(-1)m(-1 ) vs 6.9±2.5Nmkg(-1)m(-1 ) ) and lateral flexion moments ( 12.5±2.6Nmkg(-1)m(-1 ) vs 10.6±1.9Nmkg(-1)m(-1 ) ) . They also exhibited reduced muscular endurance of the back extensors ( 103±33s vs 132±33s ) and increased knee valgus angle during a single leg decline squat on the dominant ( 9±3 ° vs 5±4 ° ) and non-dominant leg ( 9±4 ° vs 6±3 ° ) in comparison to uninjured bowlers . CONCLUSIONS Bowlers who experience greater lumbar loads during bowling , have reduced back extensor muscle endurance , and demonstrate impaired control of the lumbo-pelvic-hip complex , are at increased risk of low back injury . This combination of strength , control and biomechanical factors may be key mechanical elements of low back injury causation in adolescent fast bowlers", "OBJECTIVES This study compared sports injury incidence in young high-level athletes from various team and individual sports and investigated if sport participation patterns are linked to injuries . DESIGN Prospect i ve cohort follow-up . METHODS Pupils from a public sports school ( 12 - 19 years ) were recruited over two separate school years ( 2008 - 2009 : 42 weeks , n=199 athletes ; 2009 - 2010 : 40 weeks , n=89 athletes ) . Training and competition volume and intensity were recorded via a personal sports diary . Sports injuries ( time-loss definition ) were registered by medical staff members using a st and ardized question naire . RESULTS Injury incidence was significantly higher in team compared with individual sports ( 6.16 versus 2.88 injuries/1000h , respectively ) , as a result of a higher incidence of both traumatic ( RR=2.17 ; CI95%=1.75 - 2.70 ; p ratio of 2.00 ( CI95%=1.49 - 2.68 ; p number of competitions per 100 days was significantly higher in team sports , whereas the number of intense training sessions per 100 days was significantly lower . In team sports , the number of competitions per 100 days was positively associated with injuries ( HR=1.072 ; CI95 % [ 1.033 ; 1.113 ] ; p number of competitions per 100 days had a protective effect ( HR=0.940 ; CI95 % [ 0.893 ; 0.989 ] ; p=0.017 ) . CONCLUSIONS Team sports participation entailed a higher injury risk , whatever the injury category . Further research should eluci date the role of characteristics related to sport participation in injury causation", "AIM The aim of this study was to examine injury incidence in professional football players according to the playing positions and with a special reference to training periodization . METHODS A Spanish professional team was followed prospect ively for the 2007 - 08 and 2008 - 09 seasons and exposure times and time-loss injuries were individually recorded during all training sessions and matches . Heart rate was monitored in all training sessions . RESULTS total of 114 injuries were registered during the study period ( mean injury incidence : 6.6 injuries per 1000 hours ) . The frequency of injuries was not uniformly distributed by playing positions ( P Ligament sprains and muscle strains accounted for 50 % of all injuries and 62 % of all match absences . The highest incidence of sprains was achieved during pre-season and the beginning of the competition period . The risk to sustain a muscular strain peaked at the beginning and in the final weeks of the competition period and was related ( r=0.72 ; P mean heart rate during the training stage . CONCLUSION The results suggest that there exists a difference of injury risk according to the period of the season and therefore , injury prevention strategies should be introduced from pre-season . Moreover , training workloads should be controlled to avoid increasing the risk of muscle strains", "Introduction Numerous studies have documented the incidence and nature of injuries in professional rugby union , but few have identified specific risk factors for injury in this population using appropriate statistical methods . In particular , little is known about the role of previous short-term or longer-term match exposures in current injury risk in this setting . Objectives Our objective was to investigate the influence that match exposure has upon injury risk in rugby union . Method We conducted a seven-season ( 2006/7–2012/13 ) prospect i ve cohort study of time-loss injuries in 1253 English premiership professional players . Players ’ 12-month match exposure ( number of matches a player was involved in for ≥20 min in the preceding 12 months ) and 1-month match exposure ( number of full-game equivalent [ FGE ] matches in preceding 30 days ) were assessed as risk factors for injury using a nested frailty model and magnitude-based inferences . Results The 12-month match exposure was associated with injury risk in a non-linear fashion ; players who had been involved in fewer than ≈15 or more than ≈35 matches over the preceding 12-month period were more susceptible to injury . Monthly match exposure was linearly associated with injury risk ( hazard ratio [ HR ] : 1.14 per 2 st and ard deviation [ 3.2 FGE ] increase , 90 % confidence interval [ CI ] 1.08–1.20 ; likely harmful ) , although this effect was substantially attenuated for players in the upper quartile for 12-month match exposures ( > 28 matches ) . Conclusion A player ’s accumulated ( 12-month ) and recent ( 1-month ) match exposure substantially influences their current injury risk . Careful attention should be paid to planning the workloads and monitoring the responses of players involved in : ( 1 ) a high ( > ≈35 ) number of matches in the previous year , ( 2 ) a low ( < ≈15 ) number of matches in the previous year , and ( 3 ) a low-moderate number of matches in previous year but who have played intensively in the recent past . These findings make a major contribution to evidence -based policy decisions regarding match workload limits in professional rugby union", "Background Data from scientific literature show that about 63 % of abstract s presented at biomedical conferences will be published in full . Some studies have indicated that full publication is associated with the direction of results ( publication bias ) . No study has looked into the occurrence of publication bias in the field of addiction . Objectives To investigate whether the significance or direction of results of abstract s presented at the major international scientific conference on addiction is associated with full publication Methods The conference proceedings of the US Annual Meeting of the College on Problems of Drug Dependence ( CPDD ) , were h and search ed for abstract s of r and omized controlled trials and controlled clinical trials that evaluated interventions for prevention , rehabilitation and treatment of drug addiction in humans ( years search ed 1993–2002 ) . Data regarding the study design s and outcomes reported were extracted . Subsequent publication in peer review ed journals was search ed in MEDLINE and EMBASE data bases , as of March 2006 . Results Out of 5919 abstract s presented , 581 met the inclusion criteria ; 359 ( 62 % ) conference abstract s had been published in a broad variety of peer review ed journals ( average time of publication 2.6 years , SD + /- 1.78 ) . The proportion of published studies was almost the same for r and omized controlled trials ( 62.4 % ) and controlled clinical trials ( 59.5 % ) while studies that reported positive results were significantly more likely to be published ( 74.5 % ) than those that did not report statistical results ( 60.9 % . ) , negative or None results ( 47.1 % ) and no results ( 38.6 % ) , Abstract s reporting positive results had a significantly higher probability of being published in full , while abstract s reporting None or negative results were half as likely to be published compared with positive ones ( HR = 0.48 ; 95%CI 0.30–0.74 ) Conclusion Clinical trials were the minority of abstract s presented at the CPDD ; we found evidence of possible publication bias in the field of addiction , with negative or None results having half the likelihood of being published than positive ones", "OBJECTIVES This study examined whether high match fast bowling workloads in the short to medium term were associated with increased bowling injury rates . DESIGN Prospect i ve cohort study . METHODS Over a 15 year period , workload patterns for 235 individual fast bowlers during time periods from 5 to 26 days were examined to consider whether there was an increased injury rate during the month ( 28 days ) subsequent to the workload . RESULTS Fast bowlers who bowled more than 50 match overs in a 5 day period had a significant increase in injury over the next month compared to bowlers who bowled 50 overs or less RR 1.54 ( 95 % CI 1.04 - 2.29 ) . For periods ranging from 12 to 26 days , there was no statistically-significant increase in injury over the next month from exceeding thresholds of certain amounts of overs , although bowlers who bowled more than 100 overs in 17 days had a non-significant increase in injury over the next month RR 1.78 ( 95 % CI 0.90 - 3.50 ) . CONCLUSION There were no statistically-significant increases in subsequent injury risk for high workloads for periods of 12 - 26 days , although exceeding 100 overs in 17 days ( or less ) was associated with higher injury rates . Compression of cricket fixtures is likely to have only a minimal contribution to increased fast bowling injury rates being seen in the T20 era ( along with sudden workload increases due to transferring between forms of the game , which has been previously established as a major contributor )", "Background / aims There is a paucity of prospect i ve cohort studies investigating the incidence of low back pain ( LBP ) in rowing . We investigated ( 1 ) the prevalence and incidence of LBP among international-level rowers in New Zeal and , ( 2 ) the relationship between training volume and LBP and ( 3 ) the effect of LBP on rowers ’ ability to train and compete . Methods This was a prospect i ve cohort study of 76 New Zeal and representative rowers , including 46 men ( mean age 22 , SD=4 ) and 30 women ( mean age 21 , SD=4 ) . Data were collected using an online question naire repeated monthly for 12 months . Results The prevalence of LBP ranged from 6 % to 25 % throughout the year . The incidence of episodes of LBP was 1.67 per 1000 exposure-hours . A total of 72 episodes of LBP were reported by 40 rowers ( 53 % ) during 12 months . Of these , 45 % had an incidental effect on training . 29 % minor , 18 % moderate and 9 % had a major effect as determined by the length of time the training was interrupted . There was a high correlation between new LBP and total training hours per month ( r=0.83 , p new LBP ( OR 2.06 , 95 % CI 1.22 to 3.48 , p=0.01 ) . Age was also a risk factor , with the likelihood of developing LBP increasing for every year ( OR 1.08 , 95 % CI 1.01 to 1.15 , p=0.02 ) . Conclusions LBP is common among New Zeal and representative rowers . There is a high correlation between training load and the development of LBP", "Participation in organised , competitive physical activity by young athletes is increasing rapidly . This is concurrent with an increase in sporting injuries in the young population . This pilot study aim ed to compare the weekly volume and types of physical activity in young basketball players injured and not injured during the season . Detailed physical activity and injury data were prospect ively collected in 46 school-level basketball players aged 14 to 18 years . Participants completed physical activity logs which documented the type of physical activity undertaken , what the activity consisted of ( i.e. training , competition ) and the level at which it was played on a daily basis . Allied health staff completed a weekly injury form . Results showed that injured and uninjured athletes participated in a similar volume of total weekly physical activity over the season . However , injured athletes ( p = 0.04 ) and athletes who specifically sustained overuse injuries ( p = 0.01 ) participated in a greater amount of basketball refereeing than uninjured athletes . Based on these findings it was concluded that greater participation in running-type physical activity such as refereeing , as an addition to training and competition , may predispose the young basketball player to increased injury risk . Future research using larger sample sizes are required to further investigate the role of participation volume and type on injury occurrence in adolescent athletes . Key pointsBasketball players participating in larger amounts of running-type physical activity , in addition to regular training and competition , may be predisposed to overuse injuryFuture studies using larger sample sizes are required to investigate the precise volumes of physical activity that increase injury riskThis would assist in the development of participation guidelines to decrease the current injury rates observed in the young athletic population", "Abstract A prospect i ve cohort study was used to assess the influence of training volume on injuries sustained by 502 professional rugby union players in Engl and . Training volumes ( excluding warm-ups , cool-downs , and recovery sessions ) , player injuries , and player match exposure times were reported weekly . Higher training volumes ( > 9.1 hours per week ) did not increase the incidence of match or training injuries . However , higher training volumes did increase the severity of match injuries , particularly during the second half , and consequently result ed in a significant increase in the number of days ' absence due to match injuries . Although lower-limb injuries were the most common match and training injuries , shoulder dislocations/instabilities result ed in more days ' absence during weeks of higher training volumes , but the differences were not significant . The least number of days lost due to injuries occurred during weeks of intermediate training volumes ( 6.2–9.1 h per week ) . Training volume was not correlated with final league position . Fitness testing , defence , and rucking and mauling components were identified as being very high- or high-risk training activities . Our results provide evidence of the benefits of modifying the volume and content of rugby union training to reduce the risk associated with injuries to professional players", "Study Design Prospect i ve cohort . Background The popularity of running events is still growing , particularly among women ; however , little is known about the risk factors for running-related injuries in female runners . Objectives The aims of this study were to determine the incidence and characteristics ( site and recurrence ) of running-related injuries and to identify specific risk factors for running-related injuries among female runners training for a 5- or 10-km race . Methods Four hundred thirty-five women registered for the Marikenloop run of 5 or 10 km were recruited . Follow-up data were collected over 12 weeks using question naires , starting 8 weeks before the event and ending 4 weeks after the event . Two orthopaedic tests ( navicular drop test and extension of the first metatarsophalangeal joint ) were performed in the 8 weeks before the event . Running-related injuries , defined as running-related pain of the lower back and /or the lower extremity that restricted running for at least 1 day , were assessed at 1- , 2- , and 3-month follow-ups . Results Of 417 female runners with follow-up data ( 96 % ) , 93 runners ( 22.3 % ) reported 109 running-related injuries , mainly of the hip/groin , knee , and lower leg . Multivariable Cox regression analysis showed that a weekly training distance of more than 30 km ( hazard ratio = 3.28 ; 95 % confidence interval [ CI ] : 1.23 , 8.75 ) and a previous running injury longer than 12 months prior ( hazard ratio = 1.88 ; 95 % CI : 1.03 , 3.45 ) were associated with the occurrence of running-related injuries . Conclusion Hip/groin , knee , and lower-leg injuries were common among female runners . Only weekly training distance ( greater than 30 km ) and previous running injury ( greater than 12 months prior ) were associated with running-related injuries in female runners training for a 5- or 10-km event . Level of Evidence Etiology , 2b . J Orthop Sports Phys Ther 2016;46(6):462 - 470 . Epub 26 Apr 2016 . doi:10.2519/jospt.2016.6402", "Objectives : To determine if athletes with a self reported history of previous injury have a higher incident injury rate than athletes without a self reported injury history . Methods : A prospect i ve cohort study of Classic League soccer players playing at the level under 12 through under 18 . Injury history forms were mailed to all registering Classic League soccer players in the North Carolina Youth Soccer Association during 1997–2000 ( n = 7000 ) ; 1483 ( 19 % ) returned the baseline question naire and were followed up for injuries . Results : There were 5139 player-seasons of follow up and an estimated 171 957 athlete-exposures . More than half self reported an injury history ( 59.7 % ) . Overall , the unadjusted incidence rate was 4.6 ( 95 % confidence interval ( CI ) 4.3 to 4.9 ) incident injuries per 1000 athlete-exposures . Multivariate generalised Poisson regression modelling indicated that players with one previous injury had a twofold greater risk of incident injury ( IRR = 2.6 ; 95 % CI 2.0 to 3.3 ) , and those with two or more previous injuries had a threefold greater risk of incident injury ( IRR = 3.0 ; 95 % CI 2.3 to 3.8 ) compared with athletes with no previous injuries . Conclusions : Injury history was associated with an increased injury rate . This suggests that , even in these youth soccer players , those with an injury history may be at higher risk", "Background : Previous injury is often proposed to be a risk factor for football injury , but most studies rely on players reporting their own medical history and are thus potentially subject to recall bias . Little is known about the natural variation in injury pattern between seasons . Objectives : To study whether prospect ively recorded injuries during one season are associated with injuries sustained during the following season , and to compare injury risk and injury pattern between consecutive seasons . Methods : The medical staffs of 12 elite Swedish male football teams prospect ively recorded individual exposure and time loss injuries over two full consecutive seasons ( 2001 and 2002 ) . A multivariate model was used to determine the relation between previous injury , anthropometric data , and the risk of injury . Results : The training and match injury incidences were similar between seasons ( 5.1 v 5.3 injuries/1000 training hours and 25.9 v 22.7/1000 match hours ) , but analysis of injury severity and injury patterns showed variations between seasons . Players who were injured in the 2001 season were at greater risk of any injury in the following season compared with non-injured players ( hazard ratio 2.7 ; 95 % confidence interval 1.7 to 4.3 , p Players with a previous hamstring injury , groin injury , and knee joint trauma were two to three times more likely to suffer an identical injury in the following season , whereas no such relation was found for ankle sprain . Age was not associated with an increased injury risk . Conclusions : This study confirmed previous results showing that previous injury is an important risk factor for football injury . Overall injury incidences were similar between consecutive seasons , indicating that an injury surveillance study covering one full season can provide a reasonable overview of the injury problem among elite football players in a specific environment . However , a prolonged study period is recommended for analyses of specific injury patterns", "CONTEXT Rugby union is a physically dem and ing collision sport with high injury rates . There is a common perception that higher training loads result in greater injury risk in field-based sports . OBJECTIVES To determine injury , anthropometric , and physical-performance characteristics in junior rugby union players and investigate the interaction between training load and injury across a competitive season . DESIGN Prospect i ve cohort study . METHODS Fifty-one players ( age 19.2 ± 0.7 y ) from an under-20 university rugby union team ( forwards , n = 27 ; backs , n = 24 ) participated in a study conducted over a competition season . Training load , injury characteristics , anthropometry , physiological performance , and match time-loss injury incidence were observed . RESULTS Backs had significantly lower body mass ( ES [ 95 % CI ] = 1.6 [ 0.9 , 2.2 ] ) , skinfold thickness ( ES = 1.1 [ 0.5 , 1.7 ] ) , strength ( squat ES = 0.6 [ 0.0 , 1.2 ] , deadlift ES = 0.6 [ 0.0 , 1.1 ] , bench press ES = 0.9 [ 0.4 , 1.5 ] ) , lower-body power ( ES = 0.4 [ -0.2 , 1.0 ] ) , and higher maximal aerobic capacity ( ES = -0.3 [ -0.8 , 0.3 ] ) than forwards . Match injury incidence was 107.3 injuries/1000 player hours ( forwards 91.4/1000 , backs 125.5/1000 ) during preseason and 110.7 injuries/1000 player hours ( forwards 124.1/1000 , backs 95.2/1000 ) during in-season . Forwards showed higher incidence of joint and ligament ( P = .049 ) and upper-limb ( P = .011 ) injuries than backs . No significant relationship between overall training load and match injury incidence was found . However , lower match injury incidence was associated with higher weekly training volume in backs ( P = .007 ) . CONCLUSIONS Positional differences in body composition , performance , injury characteristics , and match injury patterns were identified in junior university rugby union players , indicating the need for position-specific training programs to reduce risk of injury", "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", "Abstract Purpose In the season 2008–2009 , a third professional football league was established in Germany . This study analysed the influence of increased training and playing intensity on severe knee injuries in football players . Methods In a prospect i ve controlled one-season trial , injury incidence and injury patterns of players of the newly established professional football league were analysed , particularly with regard to ruptures of the anterior ( ACL ) and posterior ( PCL ) cruciate ligaments . Players of the highest amateur level served as a control group . Results Four hundred and eight players of 24 teams were allocated to two groups . The overall training exposure was significantly ( p overall injury rates and injury patterns . However , players in the professional league had a significantly higher ( p = 0.04 ) incidence of ACL and PCL injuries , than players at the amateur level . More than 90 % of all ACL and PCL ruptures in both groups were sustained by players , who had played at least one level lower in the previous season . In addition , injuries of players who had sustained repeat injuries over the season were more severe . Conclusion The introduction of a new professional football league increased the training and playing intensity of players as well as the number of ACL and PCL ruptures . A specific injury prevention concept , particularly for players facing rapidly increasing training and playing intensity , seems to be m and atory . Level of evidence Prospect i ve controlled cohort study , Level II", "Objectives : To investigate if reductions in pre-season training loads reduced the incidence of training injuries in rugby league players , and to determine if the reductions in training loads compromised the improvements in physical fitness obtained during the pre-season preparation period . Methods : A total of 220 sub-elite rugby league players participated in this 3 year prospect i ve study . Players underwent measurements of speed , muscular power , and maximal aerobic power before and after three 4 month ( December to March ) pre-season preparation periods ( 2001–2003 ) . A periodised skills and conditioning program was implemented , with training loads progressively increased in the general preparatory phase of the season ( December to February ) and reduced slightly in March in preparation for the competitive phase of the season . Training loads were calculated by multiplying the training session intensity by the duration of the training session . Following the initial season ( 2001 ) , training loads were reduced through reductions in training duration ( 2002 ) and training intensity ( 2003 ) . The incidence of injury was prospect ively recorded over the three pre-season periods . Results : The training loads for the 2002 and 2003 pre-season periods were significantly lower ( p The incidence of injury was significantly higher in the 2001 pre-season than the 2002 and 2003 pre-season periods . The increases in maximal aerobic power progressively improved across the three seasons with a 62–88 % probability that the 2002 and 2003 pre-season improvements in maximal aerobic power were of greater physiological significance than the 2001 pre-season improvements in maximal aerobic power . Conclusions : These findings demonstrate that reductions in pre-season training loads reduce training injury rates in rugby league players and result in greater improvements in maximal aerobic power ", "OBJECTIVES To examine the relationship between chronic training loads , number of exposures to maximal velocity , the distance covered at maximal velocity , percentage of maximal velocity in training and match-play and subsequent injury risk in elite Gaelic footballers . DESIGN Prospect i ve cohort design . METHODS Thirty-seven elite Gaelic footballers from one elite squad were involved in a one-season study . Training and game loads ( session-RPE multiplied by duration in min ) were recorded in conjunction with external match and training loads ( using global positioning system technology ) to measure the distance covered at maximal velocity , relative maximal velocity and the number of player exposures to maximal velocity across weekly periods during the season . Lower limb injuries were also recorded . Training load and GPS data were modelled against injury data using logistic regression . Odds ratios ( OR ) were calculated based on chronic training load status , relative maximal velocity and number of exposures to maximal velocity with these reported against the lowest reference group for these variables . RESULTS Players who produced over 95 % maximal velocity on at least one occasion within training environments had lower risk of injury compared to the reference group of 85 % maximal velocity on at least one occasion ( OR : 0.12 , p=0.001 ) . Higher chronic training loads ( ≥4750AU ) allowed players to tolerate increased distances ( between 90 to 120 m ) and exposures to maximal velocity ( between 10 to 15 exposures ) , with these exposures having a protective effect compared to lower exposures ( OR : 0.22 p=0.026 ) and distance ( OR=0.23 , p=0.055 ) . CONCLUSIONS Players who had higher chronic training loads ( ≥4750AU ) tolerated increased distances and exposures to maximal velocity when compared to players exposed to low chronic training loads ( ≤4750AU ) . Under- and over-exposure of players to maximal velocity events ( represented by a U-shaped curve ) increased the risk of injury", "Objective To estimate the incidence , type and severity of musculoskeletal injuries in youth and adult elite athletics athletes and to explore risk factors for sustaining injuries . Design Prospect i ve cohort study conducted during a 52-week period . Setting Male and female youth and adult athletics athletes ranked in the top 10 in Sweden ( n=292 ) . Results 199 ( 68 % ) athletes reported an injury during the study season . Ninety-six per cent of the reported injuries were non-traumatic ( associated with overuse ) . Most injuries ( 51 % ) were severe , causing a period of absence from normal training exceeding 3 weeks . Log-rank tests revealed risk differences with regard to athlete category ( p=0.046 ) , recent previous injury ( > 3 weeks time-loss ; p=0.039 ) and training load rank index ( TLRI ; p=0.019 ) . Cox proportional hazards regression analyses showed that athletes in the third ( HR 1.79 ; 95 % CI 1.54 to 2.78 ) and fourth TLRI quartiles ( HR 1.79 ; 95 % CI 1.16 to 2.74 ) had almost a twofold increased risk of injury compared with their peers in the first quartile and interaction effects between athlete category and previous injury ; youth male athletes with a previous serious injury had more than a fourfold increased risk of injury ( HR=4.39 ; 95 % CI 2.20 to 8.77 ) compared with youth females with no previous injury . Conclusions The injury incidence among both youth and adult elite athletics athletes is high . A training load index combing hours and intensity and a history of severe injury the previous year were predictors for injury . Further studies on measures to quantify training content and protocol s for safe return to athletics are warranted", "OBJECTIVES To investigate the association between training-related characteristics and running-related injury using a new conceptual model for running-related injury generation , focusing on the synergy between training load and previous injuries , short-term running experience or body mass index ( > or Recreational runners ( n = 517 ) reported information about running training characteristics ( weekly distance , frequency , speed ) , other sport participation and injuries on a dedicated internet platform . Weekly volume ( dichotomized into session frequency ( dichotomized into One hundred sixty-seven runners reported a running-related injury . Crude analyses revealed that weekly volume weekly session frequency increased injury rate . Previous injury was identified as an effect-measure modifier on weekly volume ( relative excess risk due to interaction = 4.69 ; 95 % confidence intervals = 1.42 ; 7.95 ; p = 0.005 ) and session frequency ( relative excess risk due to interaction = 2.44 ; 95 % confidence intervals = 0.48 ; 4.39 ; p = 0.015 ) . A negative synergy was found between body mass index and weekly volume ( relative excess risk due to interaction = -2.88 ; 95 % confidence intervals = -5.10 ; -0.66 ; p = 0.018 ) . CONCLUSIONS The effect of a runner 's training load on running-related injury is influenced by body mass index and previous injury . These results show the importance to distinguish between confounding and effect-measure modification in running-related injury research", "OBJECTIVES The incidence of running-related injuries is high . Some risk factors for injury were identified in novice runners , however , not much is known about the effect of training factors on injury risk . Therefore , the purpose of this study was to examine the associations between training factors and running-related injuries in novice runners , taking the time varying nature of these training-related factors into account . DESIGN Prospect i ve cohort study . METHODS 1696 participants completed weekly diaries on running exposure and injuries during a 6-week running program for novice runners . Total running volume ( min ) , frequency and mean intensity ( Rate of Perceived Exertion ) were calculated for the seven days prior to each training session . The association of these time-varying variables with injury was determined in an extended Cox regression analysis . RESULTS The results of the multivariable analysis showed that running with a higher intensity in the previous week was associated with a higher injury risk . Running frequency was not significantly associated with injury , however a trend towards running three times per week being more hazardous than two times could be observed . Finally , lower running volume was associated with a higher risk of sustaining an injury . CONCLUSIONS These results suggest that running more than 60min at a lower intensity is least injurious . This finding is contrary to our expectations and is presumably the result of other factors . Therefore , the findings should not be used plainly as a guideline for novices . More research is needed to establish the person-specific training patterns that are associated with injury", "One hundred-eighty players in a male soccer senior division of 12 teams were observed prospect ively for 1 year to study the risk of soccer injuries in relation to exposure and to establish the connection between training , injuries , and team success . Totally , more than 100 hours of practice were analyzed . All injuries were examined by the same orthopaedic surgeon . On the average , each team played 36 games and had 95 practice sessions with 66 % attendance of selected players . A direct correlation was noted be tween team success and the amount of training . Teams with more than average training showed a diminishing number of injuries . A high practice -to- game ratio seems to be advantageous . One injury every third game and every ninth practice session was documented . For the individual player the incidence of injury was 7.6/1000 practice hours and 16.9/1000 game hours . The incidence of injury was higher at training camps . Correlation was noted between the design of the train ing and the incidence of injuries . The duration of warming up seemed adequate , but its content did not appear to be satisfactory from a clinical point of view . Re design of the warm-up with more emphasis on flexibility and the addition of a cool-down is suggested to reduce injuries", "OBJECTIVES To investigate the relationship between training load and injury in professional rugby league players ; DESIGN Prospect i ve cohort study ; METHODS Seventy-nine professional rugby league players ( mean±SD age , 23.3±3.8 years ) participated in this four-year study . A periodized field , strength , and power training program was implemented , with training loads progressively increased in the general preparatory phase of the season and reduced during the competitive phase of the season . Training loads and injuries were recorded for each training session . RESULTS Training load was significantly related ( P overall injury ( r=0.82 ) , non-contact field injury ( r=0.82 ) , and contact field injury ( r=0.80 ) rates . Significant relationships were also observed between the field training load and overall field injury ( r=0.68 ) , non-contact field injury ( r=0.65 ) , and contact field injury ( r=0.63 ) rates . Strength and power training loads were significantly related to the incidence of strength and power injuries ( r=0.63 ) . There was no significant relationship between field training loads and the incidence of strength and power injuries . However , strength and power training loads were significantly ( P with the incidence of contact ( r=0.75 ) and non-contact ( r=0.82 ) field training injuries . CONCLUSIONS These findings suggest that the harder rugby league players train , the more injuries they will sustain , and that high strength and power training loads may contribute indirectly to field injuries . Monitoring of training loads and careful scheduling of field and gymnasium sessions to avoid residual fatigue is warranted to minimize the effect of training-related injuries on professional rugby league players", "PURPOSE This study aim ed to determine the association between injury history at enrollment and incident lower extremity ( LE ) injury during cadet basic training among first-year military cadets . METHODS Medically treated LE injuries during cadet basic training documented in the Defense Medical Surveillance System were ascertained in a prospect i ve cohort study of three large US military academies from 2005 to 2008 . Both acute injuries ( International Classification of Disease , Ninth Revision , codes in the 800 - 900s , including fracture , dislocations , and sprains/strains ) and injury-related musculoskeletal injuries ( International Classification of Disease , Ninth Revision , codes in the 700s , including inflammation and pain , joint derangement , stress fracture , sprain/strain/rupture , and dislocation ) were included . Risk ratio ( RR ) and 95 % confidence interval ( CI ) were computed using multivariate log-binomial models stratified by gender . RESULTS During basic training , there were 1438 medically treated acute and 1719 musculoskeletal-related LE injuries in the 9811 cadets . The most frequent LE injuries were sprains/strains ( 73.6 % of acute injuries ) and inflammation and pain ( 89.6 % of musculoskeletal-related injuries ) . The overall risk of incident LE injury was 23.2 % ( 95 % CI = 22.3%-24.0 % ) . Cadets with a history of LE injury were at increased risk for incident LE injury . This association was identical in males ( RR = 1.74 , 95 % CI = 1.55 - 1.94 ) and females ( RR = 1.74 , 95 % CI = 1.52 - 1.99 ) . In site-specific analyses , strong associations between injury history and incident injury were observed for hip , knee ligament , stress fracture , and ankle sprain . Injury risk was greater ( P injury risk in females ( RR = 2.19 , 95 % CI = 2.04 - 2.36 ) was independent of injury history ( adjusted RR = 2.09 , 95 % CI = 1.95 - 2.24 ) . CONCLUSION Injury history upon entry to the military is associated with the incidence of LE injuries sustained during cadet basic training . Prevention programs targeted at modifiable factors in cadets with a history of LE injury should be considered", "Background Although player fatigue and playing intensity have been suggested to contribute to injuries in rugby league players , no study has confirmed if the level of physical fitness is a risk factor for injury in rugby league players . The aim of this study was to identify risk factors for injury in subelite rugby league players . Hypothesis Low physical fitness levels are risk factors for injury in subelite rugby league players . Study Design Cohort study ; Level of evidence , 2 . Methods One hundred fifty-three players from a subelite rugby league club underwent preseason measurements of muscular power ( vertical jump ) , speed ( 10- and 40-m sprint ) , and maximal aerobic power ( multistage fitness test ) over 4 competitive seasons . All injuries sustained by players were prospect ively recorded over the 4 competitive seasons . Results The risk of injury was greater in players with low 10- and 40-m speed . Players with a low maximal aerobic power had a greater risk of sustaining a contact injury . In addition , players who completed less than 18 weeks of training before sustaining their initial injuries were at greater risk of sustaining a subsequent injury . Conclusions Subelite rugby league players with low speed and maximal aerobic power are at an increased risk of injury . In addition , players who complete less than 18 weeks of training before sustaining an initial injury are at greater risk of sustaining a subsequent injury . These findings highlight the importance of speed and endurance training to reduce the incidence of injury in subelite rugby league players", "OBJECTIVES Rugby league ( RL ) is a physically dem and ing collision sport , yet few studies describe injuries at the junior level despite their potential impact on career pathways and long-term health . With the absence of an injury surveillance paradigm in junior competition , this study aim ed to investigate injury incidence in an Australian setting . DESIGN Prospect i ve cohort study . METHODS A set of injury surveillance forms were developed and used to record injury characteristics , mechanism , severity and follow-up throughout one season . RESULTS Junior RL players ( n=368 , age : 15.8±1.0 years ) from 15 clubs provided baseline information . Of these , approximately six clubs ( n=122 ) provided longitudinal injury data . A total of 109 injuries ( 90 % match-related ) were recorded , with the tackle accounting for 61 % . Injury incidence ( 37.1 injuries per 1000 match hours ) was consistent with previous literature . Most injuries did not result in missed matches . The ankle and head/face were most frequently injured ( both 13 % ) , with ankle injuries leading to the highest losses of match-play . Contusions were common ( 38 % ) , although ligament injuries caused the greatest match-play losses . Injury site significantly differed between forwards and backs ( p=0.003 ) , with forwards sustaining more head/face and sternum injuries , and backs more ankle injuries . Injury type ( p=0.25 ) and severity ( p=0.09 ) were similar between positions . CONCLUSIONS Given the ongoing biological maturation in adolescent players and the injury risks related to RL , playing intensity , training regimes and injury incidence warrant rigorous documentation and monitoring . This study argues for functional but low-burden injury surveillance systems ( e.g. electronic platforms ) to be developed and implemented in junior RL", "PURPOSE To investigate the ability of various internal and external training-load ( TL ) monitoring measures to predict injury incidence among positional groups in professional rugby league athletes . METHODS TL and injury data were collected across 3 seasons ( 2013 - 2015 ) from 25 players competing in National Rugby League competition . Daily TL data were included in the analysis , including session rating of perceived exertion ( sRPE-TL ) , total distance ( TD ) , high-speed-running distance ( > 5 m/s ) , and high-metabolic-power distance ( HPD ; > 20 W/kg ) . Rolling sums were calculated , nontraining days were removed , and athletes ' corresponding injury status was marked as \" available \" or \" unavailable . \" Linear ( generalized estimating equations ) and nonlinear ( r and om forest ; RF ) statistical methods were adopted . RESULTS Injury risk factors varied according to positional group . For adjustables , the TL variables associated most highly with injury were 7-d TD and 7-d HPD , whereas for hit-up forwards they were sRPE-TL ratio and 14-d TD . For outside backs , 21- and 28-d sRPE-TL were identified , and for wide-running forwards , sRPE-TL ratio . The individual RF models showed that the importance of the TL variables in injury incidence varied between athletes . CONCLUSIONS Differences in risk factors were recognized between positional groups and individual athletes , likely due to varied physiological capacities and physical dem and s. Furthermore , these results suggest that robust machine-learning techniques can appropriately monitor injury risk in professional team-sport athletes", "OBJECTIVES To assess the association between workload , subjective wellness , musculoskeletal screening measures and non-contact injury risk in elite Australian footballers . DESIGN Prospect i ve cohort study . METHODS Across 4 seasons in 70 players from one club , cumulative weekly workloads ( acute ; 1 week , chronic ; 2- , 3- , 4-week ) and acute : chronic workload ratio 's ( ACWR : 1-week load/average 4-weekly load ) for session-Rating of Perceived Exertion ( sRPE ) and GPS-derived distance and sprint distance were calculated . Wellness , screening and non-contact injury data were also documented . Univariate and multivariate regression models determined injury incidence rate ratios ( IRR ) while accounting for interaction/moderating effects . Receiver operating characteristics determined model predictive accuracy ( area under curve : AUC ) . RESULTS Very low cumulative chronic ( 2- , 3- , 4- week ) workloads were associated with the greatest injury risk ( univariate IRR=1.71 - 2.16 , 95 % CI=1.10 - 4.52 ) in the subsequent week . In multivariate analysis , the interaction between a low chronic load and a very high distance ( adj-IRR=2.60 , 95 % CI=1.07 - 6.34 ) or low sRPE ACWR ( adj-IRR=2.52 , 95 % CI=1.01 - 6.29 ) was associated with increased injury risk . Subjectively reporting \" yes \" ( vs. \" no \" ) for old lower limb pain and heavy non-football activity in the previous 7 days ( multivariate adj-IRR=2.01 - 2.25 , 95 % CI=1.02 - 4.95 ) and playing experience ( > 9 years ) ( multivariate adj-IRR=2.05 , 95 % CI=1.03 - 4.06 ) was also associated with increased injury risk , but screening data were not . Predictive capacity of multivariate models was significantly better than univariate ( AUCmultivariate=0.70 , 95 % CI 0.64 - 0.75 ; AUCunivariate range=0.51 - 0.60 ) . CONCLUSIONS Chronic load is an important moderating factor in the workload-injury relationship . Low chronic loads coupled with low or very high ACWR are associated with increased injury risk", "OBJECTIVES To examine different timeframes for calculating acute to chronic workload ratio ( ACWR ) and whether this variable is associated with intrinsic injury risk in elite Australian football players . DESIGN Prospect i ve cohort study . METHODS Internal ( session rating of perceived exertion : sRPE ) and external ( GPS distance and sprint distance ) workload and injury data were collected from 70 players from one AFL club over 4 seasons . Various acute ( 1 - 2 weeks ) and chronic ( 3 - 8 weeks ) timeframes were used to calculate ACWRs : these and chronic load categories were then analysed to determine the injury risk in the subsequent month . Poisson regression with robust errors within a generalised estimating equation were utilised to determine incidence rate ratios ( IRR ) . RESULTS Altering acute and /or chronic timeframes did not improve the ability to detect high injury risk conditions above the commonly used 1:4 week ACWR . Twenty-seven ACWR/chronic load combinations were found to be \" high risk conditions \" ( IRR>1 , p chronic load was low or very low and ACWR was either low ( 1.5 ) . Once a high injury risk condition was entered , the elevated risk persisted for up to 28 days . CONCLUSIONS Injury risk was greatest when chronic load was low and ACWR was either low or high . This heightened risk remained for up to 4 weeks . There was no improvement in the ability to identify high injury risk situations by altering acute or chronic time periods from 1:4 weeks" ]

[ "Abstract Although medical hypnosis has a long history of myriad functional applications ( pain reduction , procedural preparation etc . ) , it has been little tested for site-specific effects on physical healing per se . In this r and omized controlled trial , we compared the relative efficacy of an adjunctive hypnotic intervention , supportive attention , and usual care only on early post-surgical wound healing . Eighteen healthy women presenting consecutively for medically recommended reduction mammaplasty at an ambulatory surgery practice underwent the same surgical protocol and postoperative care following preoperative r and omization ( n = 6 each ) to one of the three treatment conditions : usual care , 8 adjunctive supportive attention sessions , or 8 adjunctive hypnosis sessions targeting accelerated wound healing . The primary outcome data of interest were objective , observational measures of incision healing made at 1,7 weeks postoperatively by medical staff blind to the participants ' group assignments . Data included clinical exams and digitized photographs that were scored using a wound assessment inventory ( WAI ) . Secondary outcome measures included the participants ' subjectively rated pain , perceived incision healing ( VAS Scales ) , and baseline and post-surgical functional health status ( SF-36 ) . Analysis of variance showed the hypnosis group 's objective ly observed wound healing to be significantly greater than the other two groups ' , p of healing . In addition , at both the 1 and 7 week post-surgical observation intervals , one-way analyses showed the hypnosis group to be significantly more healed than the usual care controls , p assessment s of postoperative pain , incision healing and functional recovery trended similarly . Results of this preliminary trial indicate that use of a targeted hypnotic intervention can accelerate postoperative wound healing and suggest that further tests of using hypnosis to augment physical healing are warranted", "This study aim ed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g ascorbic acid ( AA ) and 0.2 g pantothenic acid ( PA ) . 49 patients undergoing surgery for tattoos , by the successive resections procedure , entered a double-blind , prospect i ve and r and omized study . Tests performed on both skin and scars determined : hydroxyproline concentrations , number of fibroblasts , trace element contents and mechanical properties . In the 18 supplemented patients , it was shown that in skin ( day 8) Fe increased ( p Mn decreased ( p scars ( day 21 ) , Cu ( p = 0.07 ) and Mn ( p Mg ( p mechanical properties of scars in group A were significantly correlated to their contents in Fe , Cu and Zn , whereas no correlation was shown in group B. In blood , AA increased after surgery with supplementation , whereas it decreased in controls . Although no major improvement of the would healing process could be documented in this study , our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements , as they are correlated to mechanical properties of the scars", "OBJECTIVES Psychological stress is believed to impair wound healing via a down-regulation of the immune system . Since previous research suggests that disclosure of tra-umatic experiences can result in an up-regulation of immune function , the present study aim ed to investigate the impact of a disclosure intervention on the progress of wound healing . DESIGN The study used a prospect i ve , longitudinal design with r and om assignment to the control ( writing about time management ) and experimental group ( writing about a traumatic event ) . METHODS Participants ( N=36 ) completed question naires measuring perceived and emotional distress , loneliness , self-esteem , social support , dispositional optimism , and health-related behaviours . Accurate indication of the healing of a small punch biopsy wound was determined by using a high-resolution ultrasound scanner . RESULTS Repeated measures ANOVA indicated that the disclosure intervention impacted wound healing . Participants who wrote about traumatic events had significantly smaller wounds 14 and 21 days after the biopsy compared with those who wrote about time management . CONCLUSIONS It is concluded that a relatively brief and easy to administer intervention can have beneficial effects on wound healing . The potential for use in patient sample s is indicated", "Objective : To examine the effect of a brief laboratory stressor and social support before the stressor on cardiovascular and cortisol responses , and skin barrier recovery after skin disruption . Methods : Eighty-five healthy participants ( mean age 22.9 ± 4.4 years ) underwent a “ tape-stripping ” procedure that disrupts normal skin barrier function , and were r and omly assigned to a No Stress ( reading task ) , Stress ( Trier Social Stress Test ) , or Stress + Social Support condition ( support from a confederate before the stressor ) . Skin barrier recovery was assessed by measuring transepidermal water loss from up to 2 hours after skin disruption . Results : Compared with the No Stress condition , the stressor delayed skin barrier recovery by 10 % at 2 hours after skin disruption ( effect size , r = .29 ) , and increased anxiety ( r = .24 ) , negative affect ( r = .22 ) , cardiovascular activity ( r values from .4–.6 ) , and among male participants , cortisol levels ( r = .40 ) . Social support did not influence psychological or physiological responses or skin barrier recovery . Larger physiological responses to the tasks did not predict slower skin barrier recovery . Instead , larger systolic blood pressure responses predicted faster skin barrier recovery ( r = .26 ) . Conclusions : This study replicated the effects of short-term laboratory stressors on skin barrier recovery , further establishing the relevance of skin barrier recovery for future research . The support manipulation did not influence physiological responses or skin barrier recovery , suggesting that future research on social support , physiology , and objective health outcomes should focus on naturalistic social interactions , relationships , and stressors . AUCI = area under the curve with respect to increase ; BMI = body mass index ; DBP = diastolic blood pressure ; GCRC = General Clinical Research Center ; HR = heart rate ; MAP = mean arterial pressure ; SBP = systolic blood pressure ; TSST = Trier Social Stress Test ; TEWL = transepidermal water loss", "Following traumatic or surgical injury to the skin , wounds do not heal by tissue regeneration but rather by scar formation . Though healing is definitely a welcomed event , the result ant scar , very often , is not aesthetically pleasing , and not infrequently , may be pathologic causing serious deformities and contractures . Management of problematic scars continues to be a frustrating endeavor with less than optimal results . Prophylactic methods of wound management to minimize serious scarring are being developed . In a previously published study , we have demonstrated improved healing of split thickness skin graft donor sites following treatment with Moist Exposed Burn Ointment ( MEBO , Julphar Gulf Pharmaceutical Industries , Ras Al-Kh aim ah , UAE ) . At present , we are reporting the results of a comparative clinical prospect i ve study evaluating scar quality following primary healing of elective surgical and traumatic facial wounds with prophylactic MEBO application , topical antibiotic ointment application , and no topical therapy at all . Scars were evaluated according to the Visual Analogue Scale for scar assessment . Statistical analysis of scar assessment scores demonstrated marked prevention of unfavorable scars with improved cosmetic results following MEBO prophylactic therapy", "OBJECTIVE This study aims to evaluate the influence of an empathic patient-centered approach on preoperative anxiety and surgical outcomes in ambulatory surgery patients . METHODS A sample of 104 patients undergoing general ambulatory surgery was r and omly assigned to the intervention ( IG ) and the control ( CG ) groups . Before surgery , the IG received personalized information through an empathic patient-centered interview . The CG received st and ardized information on surgical procedures . Anxiety was assessed before and after the preoperative interview and after the surgery . Wound healing , post-surgical recovery and satisfaction with the quality of preoperative information were assessed after the surgery . RESULTS The two groups were identical at baseline regarding anxiety , socio-demographic and clinical characteristics . After the patient-centered intervention , the IG showed lower levels of preoperative anxiety ( p pain ( p better surgery recovery ( p higher levels of daily activity ( p satisfaction with the information received ( p better wound healing ( tissue type , p empathic patient-centered intervention can reduce preoperative anxiety and increase surgical recovery , wound healing and patient satisfaction . PRACTICE IMPLICATION S This approach is applicable in pre-surgical interviews and can potentially be used in the routine care of various surgical context", "BACKGROUND Bacterial destruction caused by free radicals , which are synthesized by neutrophils in the presence of oxygen , depends on adequate tissue perfusion . Mild perioperative hypothermia causes vasoconstriction , reducing nutrient and oxygen supply to wounds and increasing frequency of surgical wound infection . However , the causal role of hypothermia in surgical wound infection is the subject of controversy . The present work proposes the hypothesis that mild perioperative hypothermia is associated with infection of the surgical wound . METHODS A prospect i ve cohort of 290 surgical patients was studied in a second-level hospital ; 261 ( 90 % ) of the patients concluded the follow-up . The relationship of hypothermia and of other confounding factors , such as diabetes mellitus , antibiotic treatment , and wound drains with infection outcome was evaluated . One physician , blinded to patient hypothermia , gathered the data . Surgical wound infection was defined as the surgeon 's diagnosis with positive culture . RESULTS Twenty subjects ( 7.6 % ) showed infection of surgical wound ; 18 ( 11.5 % ) of 156 hypothermics and two ( 2 % ) 105 normothermics ( p = 0.004 ) . Hypothermia proved to be a significant independent risk of infection with relative risk of 6.3 ( p = 0.01 ) . CONCLUSIONS Mild perioperative hypothermia is associated with infection of the surgical wound and its prevention is therefore justified", "Psychological stress has been shown to impair wound healing , but experimental research in surgical patients is lacking . This study investigated whether a brief psychological intervention could reduce stress and improve wound healing in surgical patients . This r and omised controlled trial was conducted at a surgical centre . Inclusion criteria were English-speaking patients over 18 years booked to undergo elective laparoscopic cholecystectomy ; exclusion criteria were cancellation of surgery , medical complications , and refusal of consent . Seventy five patients were r and omised and 15 patients were excluded ; 60 patients completed the study ( 15 male , 45 female ) . Participants were r and omised to receive st and ard care or st and ard care plus a 45-min psychological intervention that included relaxation and guided imagery with take-home relaxation CDs for listening to for 3 days before and 7 days after surgery . In both groups ePTFE tubes were inserted during surgery and removed at 7 days after surgery and analysed for hydroxyproline as a measure of collagen deposition and wound healing . Change in perceived stress from before surgery to 7-day follow-up was assessed using question naires . Intervention group patients showed a reduction in perceived stress compared with the control group , controlling for age . Patients in the intervention group had higher hydroxyproline deposition in the wound than did control group patients ( difference in means 0.35 , 95 % CI 0.66 - 0.03 ; t(43)=2.23 , p=0.03 ) . Changes in perceived stress were not associated with hydroxyproline deposition . A brief relaxation intervention prior to surgery can reduce stress and improve the wound healing response in surgical patients . The intervention may have particular clinical application for those at risk of poor healing following surgery", "BACKGROUND One of the main problems of elective surgery is the cosmetic result . OBJECTIVE This prospect i ve controlled study aims to determine the effects of topical vitamin E on cosmetic results in children . METHODS A single-blind study was carried out . Topical vitamin E was used on the intended incision site for at least 15 days , thrice daily , before surgery and for at least 30 days , twice daily , after surgery ( group A ) . The control group received topical petrolatum-based ointment ( group B ) . RESULTS No patients in group A developed keloids . A total of 96 % of patients ( or parents ) considered the cosmetic results very good . No patients had wound infection . In the control group , only 78 % of patients ( or parents ) considered the cosmetic results very good and 13 ( 6.5 % ) patients developed keloids after 6 months . There were no cases of wound infection . CONCLUSION Topical vitamin E before and after surgery improved surgical wound healing and improved cosmetic results", "BACKGROUND Wound infection after clean surgery is an expensive and often underestimated cause of patient morbidity , and the benefits of using prophylactic antibiotics have not been proven . Warming patients during colorectal surgery has been shown to reduce infection rates . We aim ed to assess whether warming patients before short duration , clean surgery would have the same effect . METHODS 421 patients having clean ( breast , varicose vein , or hernia ) surgery were r and omly assigned to either a non-warmed ( st and ard ) group or one of two warmed groups ( local and systemic ) . We applied warming for at least 30 min before surgery . Patients were followed up and masked outcome assessment s made at 2 and 6 weeks . FINDINGS Analysis was done on an intention-to-treat basis . We identified 19 wound infections in 139 non-warmed patients ( 14 % ) but only 13 in 277 who received warming ( 5 % ; p=0.001 ) . Wound scores were also significantly lower ( p=0.007 ) in warmed patients . There was no significant difference in the development of haematomas or seromas after surgery but the non-warmed group were prescribed significantly more postoperative antibiotics ( p=0.002 ) . INTERPRETATION Warming patients before clean surgery seems to aid the prevention of postoperative wound infection . If applied according to the manufacturers guidelines these therapies have no known side-effects and might , with the support of further studies , provide an alternative to prophylactic antibiotics in this type of surgery", "Objective : In addition to a preoperative antibiotic single-shot prophylaxis , we tested the impact of a one-time preoperative water-filtered infrared A irradiation ( wIRA ) on postoperative wound healing of patients . Background : wIRA improves wound healing in postoperative setting s. Methods : A total of 400 consecutive patients undergoing gastrointestinal surgery were r and omly assigned to the treatment group ( A ) or placebo group ( B ) . We applied wIRA for 20 minutes while patients were prepared for surgery . Patients and observer were blinded to group assignment . Primary endpoints were surgical site infections ( SSIs ) , wound healing , and rate and level of pain within 30 days after surgery . Primary efficacy analysis was carried out on the basis of an intention-to-treat ( ITT ) population and a full- analysis set ( FAS ) . Missing values of primary outcome variables were considered as SSIs and maximum pain levels in the ITT analysis , respectively . Results : FAS : The incidence of SSI was 9 of 178 patients ( 5.1 % ) within group A compared with 22 of 182 ( 12.1 % ) within group B [ P = 0.018 ; relative risk ( RR ) = 0.42 ; 95 % CI : 0.18–0.93 ] . ITT : 32 of 200 ( 16 % ) SSIs occurred within group A and 39 of 200 ( 20 % ) within group B ( P = 0.248 ) with an RR of 0.74 ( 95 % CI : 0.43–1.28 ) . The wIRA group showed lower postoperative pain at both the ITT ( P = 0.092 ) and the FAS analysis ( P = 0.045 ) . Conclusions : This trial indicates a clinical ly relevant benefit of one-time application of preoperative wIRA as a supportive addition to prophylactic antibiotics . wIRA contributes to both reduced SSI rates and postoperative pain but also effectively decreases morbidity and related expenses in the health care system", "Objective To investigate whether expressive writing could speed wound reepithelialization in healthy , older adults . Methods In this r and omized controlled trial , 49 healthy older adults aged 64 to 97 years were assigned to write for 20 minutes a day either about up setting life events ( Expressive Writing ) or about daily activities ( Time Management ) for 3 consecutive days . Two weeks postwriting , 4-mm punch biopsy wounds were created on the inner , upper arm . Wounds were photographed routinely for 21 days to monitor wound reepithelialization . Perceived stress , depressive symptoms , health-related behaviors , number of doctor visits , and lipopolysaccharide-stimulated proinflammatory cytokine production were also measured throughout the study . Results Participants in the Expressive Writing group had a greater proportion of fully reepithelialized wounds at Day 11 postbiopsy compared with the Time Management group , with 76.2 % versus 42.1 % healed , & khgr;2(1 , n = 40 ) = 4.83 , p = .028 . Ordinal logistic regression showed more sleep in the week before wounding also predicted faster healing wounds . There were no significant group differences in changes to perceived stress , depressive symptoms , health-related behaviors , lipopolysaccharide-induced proinflammatory cytokine production , or number of doctor visits over the study period . Conclusions This study extends previous research by showing that expressive writing can improve wound healing in older adults and women . Future research is needed to better underst and the underlying cognitive , psychosocial , and biological mechanisms contributing to improved wound healing from these simple , yet effective , writing exercises . Trial Registration : Australian New Zeal and Clinical Trials Registry ( trial number 343095", "Context : Pre- and postoperative distress in breast cancer patients can cause complications and delay recovery from surgery . Objective : The aim of our study was to evaluate the effects of yoga intervention on postoperative outcomes and wound healing in early operable breast cancer patients undergoing surgery . Methods : Ninety-eight recently diagnosed stage II and III breast cancer patients were recruited in a r and omized controlled trial comparing the effects of a yoga program with supportive therapy and exercise rehabilitation on postoperative outcomes and wound healing following surgery . Subjects were assessed at the baseline prior to surgery and four weeks later . Sociodemographic , clinical and investigative notes were ascertained in the beginning of the study . Blood sample s were collected for estimation of plasma cytokines — soluble Interleukin (IL)-2 receptor ( IL-2R ) , tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma . Postoperative outcomes such as the duration of hospital stay and drain retention , time of suture removal and postoperative complications were ascertained . We used independent sample s t test and nonparametric Mann Whitney U tests to compare groups for postoperative outcomes and plasma cytokines . Regression analysis was done to determine predictors for postoperative outcomes . Results : Sixty-nine patients contributed data to the current analysis ( yoga : n = 33 , control : n = 36 ) . The results suggest a significant decrease in the duration of hospital stay ( P = 0.003 ) , days of drain retention ( P = 0.001 ) and days for suture removal ( P = 0.03 ) in the yoga group as compared to the controls . There was also a significant decrease in plasma TNF alpha levels following surgery in the yoga group ( P yoga intervention affected the duration of drain retention and hospital stay as well as TNF alpha levels . Conclusion : The results suggest possible benefits of yoga in reducing postoperative complications in breast cancer patients", "Postoperative surgical site infections contribute significantly to increased patient morbidity and mortality rates and unnecessary hospital costs . Effective and efficient preoperative patient skin preparation is an important perioperative nursing intervention that decreases the number of wound contaminants and reduces the risks for postoperative surgical site infections . This study examined the effectiveness and time and material costs of two preoperative patient skin prep methods ( ie , isopropyl alcohol prep/iodophor-impregnated adhesive drape method , iodophor scrub and paint prep/plain adhesive drape method ) . The isopropyl alcohol prep/iodophor-impregnated adhesive drape method clinical ly was as effective as the iodophor scrub and paint prep/plain adhesive drape method , more cost-effective when time and material s were compared , and less cost-effective when material s alone were compared . To make appropriate decisions about the use of preoperative patient skin prep methods , perioperative nurse managers and staff members need to examine and determine whether costs in time or material s have the greater impact on their surgical setting", "BACKGROUND An increased anxiety may be associated with a higher risk of surgical site infection ( SSI ) , but there is little objective data on the effect of preoperative anxiolytic interventions on SSI . To address this issue , we evaluated the effects of preoperative diazepam on postoperative SSI following abdominal hysterectomy . METHODS This r and omized , double-blinded , placebo-controlled study included 130 patients , American Society of Anesthesiologist physical status 1 or 2 . Patients were r and omly assigned to receive either oral diazepam 10 mg ( n = 65 ) or placebo ( n = 65 ) the night before and 1 hour prior to surgery . The assessment instruments were the Visual Analogue Scale and the State-Trait Anxiety Inventory . SSI was diagnosed according to the criteria of the Centers for Disease Control and Prevention with st and ard follow-up of 30 days . RESULTS The relative risk ( RR ) was 1.79 ( 95 % confidence interval [ CI ] : 1.31 - 2.43 ) , and the number of patients that needed to be treated was 5.2 ( 95 % CI : 2.74 - 50.76 ) to prevent 1 additional SSI . The RR for SSI in placebo-treated patients with high postoperative anxiety was 1.65 ( 95 % CI : 1.07 - 2.56 ) . CONCLUSION Diazepam-treated patients showed lower postoperative anxiety and lower incidence of SSI up to 30 days after surgery compared with placebo in patients undergoing abdominal hysterectomy" ]

[ "BACKGROUND Excessive energy intake tends to increase circulating levels of insulin and free insulin-like growth factor-1 ( IGF-I ) , which may increase risk of some cancers that are common in Western countries . However , the relative importance of these hormonal factors during pre-adulthood and adulthood is unknown . METHODS We prospect ively examined height , as a marker of pre-adult IGF-I bioactivity , and modifiable adult determinants of insulin secretion , in relation to risk of cancer , particularly Western-related cancers ( colon , pancreas , kidney , and aggressive prostate cancers ) in 47,690 male health professionals . Information about dietary and lifestyle factors for these men was collected at baseline ( 1986 ) and was up date d periodically . A C-peptide score , representing insulin secretion , was created by using body mass , physical activity , and diet in a stepwise linear regression to predict C-peptide level , in a sample of 263 cohort members . RESULTS From 1986 to 1998 , we documented 3270 incident cancers ( excluding the less aggressive prostate cancers ) . Greater body mass index , lower physical activity , and a Western dietary pattern were independent predictors of higher plasma C-peptide levels in the sample . A C-peptide score , based on these variables , was positively related to risk of Western-related cancers , but not to other cancer types in the entire cohort . Height was also only related to Western-related cancers . For Western-related cancers , 29 % ( 95 % CI : 16 % , 48 % ) were attributed to C-peptide scores above the first decile , 30 % ( 95 % CI : 11 % , 58 % ) to heights > or=66 inches , and 49 % ( 95 % CI : 30 % , 69 % ) to both factors combined . For total cancers , 29 % ( 95 % CI : 16 % , 46 % ) were attributable to both factors . CONCLUSIONS Maximal growth in the pre-adult period and hyperinsulinaemia during adulthood may largely underlie the excess risk of some cancers that are common in Western population s. A substantial proportion of these cancers may be modifiable in adulthood , through alterations in body weight , sedentary behaviour , and dietary patterns that stimulate hyperinsulinaemia", "The effect of dietary fructose ( 20 % of carbohydrate calories , 45 - 65 g day-1 for 4 weeks ) on glycaemic control , serum lipid , lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients . The study was done in a r and omized , double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day . The patients were hospitalized throughout the study periods . The fasting plasma glucose concentration decreased during the fructose ( from 10.7 + /- 1.4 mmol l-1 to 8.0 + /- 0.8 mmol l-1 , P control diet ( from 10.1 + /- 0.9 mmol l-1 to 8.0 + /- 0.7 mmol l-1 , P mean diurnal blood glucose concentration also fell both during the fructose ( from 10.8 + /- 0.5 mmol l-1 to 8.4 + /- 0.3 mmol l-1 , P HbA1 concentration improved ( P Insulin sensitivity increased by 34 % ( P Serum insulin , triglyceride , apoprotein A-I and A-II concentrations , body weight , blood pressure and blood lactate remained unchanged during both diets . In conclusion , substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes" ]

[ "Dietary data from a prospect i ve study were used to relate factors influencing calcium balance ( estimates of dietary calcium intake , protein intake from nondairy animal sources ( meat , fish , and eggs ) , and coffee consumption ) to the incidence of hip fracture . During the years 1977 - 1983 , women and men born between 1925 and 1940 and living in one of three Norwegian counties were invited to a cardiovascular screening that included a dietary survey . The attendance rate at screening was 91.1 % , and 90.7 % of these persons ( 19,752 women and 20,035 men ) filled in and returned a semiquantitative dietary question naire . This cohort was followed for an average of 11.4 years ( range , 0.01 - 13.8 years ) with respect to hip fracture , defined as cervical or trochanteric fracture . During follow-up , 213 hip fractures were identified , excluding fractures associated with high-energy trauma and metastatic bone disease . There was no clear association between calcium intake or nondairy animal protein intake and hip fracture in this cohort . However , an elevated risk of fracture was found in women with a high intake of protein from nondairy animal sources in the presence of low calcium intake ( relative risk = 1.96 ( 95 % confidence interval 1.09 - 3.56 ) for the highest quarter of nondairy protein intake and the lowest quarter of calcium intake vs. the three lower quarters of protein intake and the three higher quarters of calcium intake ) . Women who drank nine or more cups of coffee per day also had an increased risk of fracture , while there was no association between coffee consumption and hip fracture in men . Although these findings do not necessarily imply causal relations , they suggest the presence of risk factors for hip fracture that act through a negative calcium balance in this population", "Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people . Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the calcium – vitamin D3 fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women", "Summary The relationship between osteoporosis risk factors , bone quantitative ultrasound ( QUS ) and non-spinal fracture risk was estimated in a cohort of 5,201 postmenopausal women from Spain who were prospect ively evaluated during three years . Several clinical risk factors and low heel QUS values were independently associated with non-spinal fracture risk . Introduction Low-trauma , non-spinal fractures are a growing source of morbidity and mortality in the elderly . The aim of the present study was to examine the association of heel quantitative ultrasound ( QUS ) and a series of osteoporosis and fracture risk factors , with incident low energy non-spinal fractures in a population of elderly women , and to incorporate them into fracture prediction models . Methods 5,201 women aged 65 or older were enrolled in a three-year cohort study . Participants completed an osteoporosis and fracture risk factors question naire . QUS was measured at the heel with a gel-coupled device . Cox-proportional hazard analyses were performed to evaluate the association with the first incident low-trauma non-spinal fracture . Results Three hundred and eleven women ( 6.0 % ) sustained a total of 363 low-trauma fractures , including 133 forearm/wrist , 54 hip , 50 humerus , 37 leg and 17 pelvic fractures . For every st and ard deviation decrease in the quantitative ultrasound index , the adjusted hazard ratios ( 95 % CI ) for any non-vertebral , hip , forearm/wrist , and humerus fractures were 1.31 ( 1.15–1.49 ) , 1.40 ( 1.01–1.95 ) , 1.50 ( 1.19–1.89 ) and 1.35 ( 0.97–1.87 ) , respectively . Similar results were observed with other QUS variables . The best predictive models indicated that age , a history of falls , a previous low-trauma fracture , a family history of fracture , a calcium intake from dairy products of less than 250 mg/day , and lower values of QUS parameters were independently associated with the risk of non-spinal fractures . Conclusions Both clinical risk factors and QUS are independent predictors of risk of fragility non-spinal fractures . A prediction algorithm using these variables was developed to estimate the absolute risk of non-spinal fractures in elderly women in Spain", "Fractures of the proximal humerus , forearm , and wrist account for approximately one third of total osteoporotic fractures in the elderly . Several risk factors for these fractures were evaluated in this prospect i ve study of 739 men and 1,105 women aged > or = 60 years in Dubbo , Australia . During follow-up ( 1989 - 1996 ) , the respective incidences of humerus and of forearm and wrist fractures , per 10,000 person-years , were 22.6 and 33.8 for men and 54.8 and 124.6 for women . Independent predictors of humerus fracture were femoral neck bone mineral density ( FNBMD ) ( relative risk ( RR ) = 2.3 , 95 % confidence interval ( CI ) : 1.2 , 4.5 ) in men and FNBMD ( RR = 2.4 , 95 % CI : 1.7 , 3.5 ) and height loss ( RR = 1.1 , 95 % CI : 1.0 , 1.2 ) in women . For forearm and wrist fractures , risk factors were FNBMD ( men : RR = 1.5 , 95 % CI : 1.0 , 2.3 ; women : RR = 1.5 , 95 % CI : 1.2 , 1.9 ) and height loss ( men : RR = 1.2 , 95 % CI : 1.0 , 1.3 ; women : RR = 1.1 , 95 % CI : 1.0 , 1.2 ) . In addition , dietary calcium ( men : RR = 2.0 , 95 % CI : 1.0 , 3.6 ) and a history of falls ( women : RR = 1.9 , 95 % CI : 1.4 , 2.6 ) were also significant . These data suggest that elderly men and women largely share common risk factors for upper limb fractures and that FNBMD is the primary risk factor", "BACKGROUND The effect of supplementation with calcium alone on risk fractures in a healthy population is not clear . OBJECTIVE The objective was to determine whether 4 y of calcium supplementation would reduce the fracture risk during treatment and subsequent follow-up in a r and omized placebo-controlled trial . DESIGN The participants were aged were r and omly assigned to receive 4 y of treatment with 3 g CaCO(3 ) ( 1200 mg elemental Ca ) daily or placebo and were followed for a mean of 10.8 y. The primary outcomes of this analysis were all fractures and minimal trauma fractures ( caused by a fall from st and ing height or lower while sitting , st and ing , or walking ) . RESULTS There were 46 fractures ( 15 from minimal trauma ) in 464 participants in the calcium group and 54 ( 29 from minimal trauma ) in 466 participants in the placebo group . The overall risk of fracture differed significantly between groups during the treatment phase [ hazard ratio ( HR ) : 0.28 ; 95 % CI : 0.09 , 0.85 ] , but not during the subsequent posttreatment follow-up ( HR : 1.10 ; 95 % CI : 0.71 , 1.69 ) . Minimal trauma fractures were also less frequent in the calcium group during treatment ( HR : 0 ; 95 % CI : 0 , 0.50 ) . CONCLUSION Calcium supplementation reduced the risk of all fractures and of minimal trauma fractures among healthy individuals . The benefit appeared to dissipate after treatment was stopped . This trial was registered at clinical trials.gov as NCT00153816", "BACKGROUND Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women ; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets . Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures . OBJECTIVE We assessed relations between postmenopausal hip fracture risk and calcium , vitamin D , and milk consumption . DESIGN In an 18-y prospect i ve analysis in 72 337 postmenopausal women , dietary intake and nutritional supplement use were assessed at baseline in 1980 and up date d several times during follow-up . We identified 603 incident hip fractures result ing from low or moderate trauma . Relative risks ( RRs ) from proportional hazards models were controlled for other dietary and nondietary factors . RESULTS Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37 % lower risk of hip fracture ( RR = 0.63 ; 95 % CI : 0.42 , 0.94 ) than did women consuming Total calcium intake was not associated with hip fracture risk ( RR = 0.96 ; 95 % CI : 0.68 , 1.34 for > or = 1200 compared with lower risk of hip fracture ( P for trend = 0.21 ) . CONCLUSIONS An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women . Neither milk nor a high-calcium diet appears to reduce risk . Because women commonly consume less than the recommended intake of vitamin D , supplement use or dark fish consumption may be prudent", "UNLABELLED This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D , especially during winter periods . INTRODUCTION We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents . MATERIAL S AND METHODS This was a factorial , cluster-r and omized , pragmatic , intervention study . We included 9605 community-dwelling residents aged 66 + years . We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU ( 10 microg ) of vitamin D3 to a total of 4957 participants . Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants . Both programs included revision of the resident 's current pharmaceutical treatment . We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Data base . We defined osteoporotic fractures as low energy fractures of the proximal humerus , distal forearm , vertebral column , pelvis , cervical femur , and intertrochanteric femur . RESULTS Active participation was 50.3 % in the Calcium and Vitamin D Program and 46.4 % in the Environmental and Health Program . We observed a 16 % reduction in fracture incidence rate ( relative risk [ RR ] , 0.84 ; CI , 0.72 - 0.98 ; p female residents offered the Calcium and Vitamin D Program ( intention-to-prevent analysis ) . CONCLUSIONS This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D , especially during winter periods", "Objective To investigate associations between long term dietary intake of calcium and risk of fracture of any type , hip fractures , and osteoporosis . Design A longitudinal and prospect i ve cohort study , based on the Swedish Mammography Cohort , including a subcohort , the Swedish Mammography Cohort Clinical . Setting A population based cohort in Sweden established in 1987 . Participants 61 433 women ( born between 1914 and 1948 ) were followed up for 19 years . 5022 of these women participated in the subcohort . Main outcome measures Primary outcome measures were incident fractures of any type and hip fractures , which were identified from registry data . Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort . Diet was assessed by repeated food frequency question naires . Results During follow-up , 14 738 women ( 24 % ) experienced a first fracture of any type and among them 3871 ( 6 % ) a first hip fracture . Of the 5022 women in the subcohort , 1012 ( 20 % ) were measured as osteoporotic . The risk patterns with dietary calcium were non-linear . The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake , and 14.0/1000 person years at risk in the third quintile , corresponding to a multivariable adjusted hazard ratio of 1.18 ( 95 % confidence interval 1.12 to 1.25 ) . The hazard ratio for a first hip fracture was 1.29 ( 1.17 to 1.43 ) and the odds ratio for osteoporosis was 1.47 ( 1.09 to 2.00 ) . With a low vitamin D intake , the rate of fracture in the first calcium quintile was more pronounced . The highest quintile of calcium intake did not further reduce the risk of fractures of any type , or of osteoporosis , but was associated with a higher rate of hip fracture , hazard ratio 1.19 ( 1.06 to 1.32 ) . Conclusion Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis", "To assess the effect of dietary calcium intake on risk of hip fracture , a geographically defined caucasian population in southern California was studied prospect ively . Between 1973 and 1975 , a quantified 24 hour diet recall was obtained by a dietician from 957 men and women aged 50 to 79 years at baseline . Follow-up to 1987 with mortality records and interviews showed 15 men and 18 women with hip fractures . The age-adjusted risk of hip fracture was inversely associated with dietary calcium whether considered as mg per day or as nutrient density ( mg per 1000 kcal ) . No other nutrient was consistently associated with hip fracture in any Cox proportional hazards model that included calcium . The association between calcium and fracture persisted after adjustment for cigarette smoking , alcohol intake , exercise , and obesity . The significant independent inverse association of dietary calcium with subsequent risk of hip fracture ( relative risk = 0.6 per 198 mg/1000 kcal ) strongly supports the hypothesis that increased dietary calcium intake protects against hip fracture", "Several epidemiological studies have identified clinical factors that predict the risk of hip fractures in elderly women independently of the level of bone mineral density ( BMD ) , such as low body weight , history of fractures , and clinical risk factors for falls . Their relevance in predicting all fragility fractures in all postmenopausal women , including younger ones , is unknown . The objective of this study was to identify independent predictors of all osteoporosis-related fractures in healthy postmenopausal women . We prospect ively followed for 5.3 + /- 1.1 years a cohort of 672 healthy postmenopausal women ( mean age 59.1 + /- 9.8 years ) . Information on social and professional conditions , demographic data , current and past medical history , fracture history , medication use , alcohol consumption , caffeine consumption , daily calcium intake , cigarette smoking , family history of fracture , and past and recent physical activity was obtained . Anthropometric and total hip bone mineral density measurements were made . Incident falls and fractures were ascertained every year . We observed 81 osteoporotic fractures ( annual incidence , 21 per 1000 women/year ) . The final model consisted of seven independent predictors of incident osteoporotic fractures : age > or = 65 years , odds ratio estimate ( OR ) , 1.90 [ 95 % confidence interval ( CI ) 1.04 - 3.46 ] , past falls , OR , 1.76 ( CI 1.00 - 3.09 ) , total hip bone mineral density ( BMD ) left grip strength maternal history of fracture , OR , 1.77 ( CI 1.01 - 3.09 ) , low physical activity , OR , 2.08 ( CI 1.17 - 3.69 ) , and personal history of fragility fracture , OR , 3.33 ( CI 1.75 - 5.66 ) . In contrast , body weight , weight loss , height loss , smoking , neuromuscular coordination assessed by three tests , and hormone replacement therapy were not independent predictors of all fragility fractures after adjustment for all variables . We found that some -- but not all -- previously reported clinical risk factors for skeletal fragility predicted all fragility fractures independently of BMD in healthy postmenopausal women , although they differed somewhat from those predicting specifically hip fractures in elderly women . These risk factors appear to reflect quality of bone structure ( previous fragility fracture ) , lifestyle habits ( physical activity ) , muscle function and health status ( grip strength ) , heredity ( maternal history of fracture ) , falls , and aging . Measurements of these variables should be included in the clinical assessment of the risk of osteoporotic fractures in postmenopausal women", "This placebo-controlled r and omized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women , 57 of whom were early postmenopausal ( five years after menopause ) and six of whom were mid-postmenopausal ( five to ten years after menopause ) . Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years . The two groups were similar in baseline age , years postmenopause ( 3.3 in the calcium citrate group vs 2.7 in the placebo group ) , height , weight , calcium intake , and L2-L4 bone density . L2-L4 bone density did not change during calcium citrate treatment ( + 1.03 % after two years ) , whereas it declined significantly by -2.38 % after two years on placebo ( P Femoral neck bone density did not change in either group . Radial shaft bone density did not change in the calcium citrate group ( -0.02 % after two years ) , but it declined significantly in the placebo group ( -1.79 % after one year and -3.03 % after two years , P in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups . An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause , but a protective effect after three years . Although serum PTH did not change , serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group , indicative of parathyroid suppression . Serum bone-specific alkaline phosphatase and osteocalcin , and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods , indicative of a reduction in bone turnover . Thus , calcium citrate supplementation ( 400 mg of calcium twice daily ) averted bone loss and stabilized bone density in the spine , femoral neck , and radial shaft in women relatively soon after menopause . This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression", "BACKGROUND AND METHODS Laboratory , clinical , and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas . We conducted a r and omized , double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas . We r and omly assigned 930 subjects ( mean age , 61 years ; 72 percent men ) with a recent history of colorectal adenomas to receive either calcium carbonate ( 3 g [ 1200 mg of elemental calcium ] daily ) or placebo , with follow-up colonoscopies one and four years after the qualifying examination . The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to ( and including ) the second follow-up examination . Risk ratios for the recurrence of adenomas were adjusted for age , sex , lifetime number of adenomas before the study , clinical center , and length of the surveillance period . RESULTS The subjects in the calcium group had a lower risk of recurrent adenomas . Among the 913 subjects who underwent at least one study colonoscopy , the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 ( 95 percent confidence interval , 0.74 to 0.98 ; P=0.03 ) . The main analysis was based on the 832 subjects ( 409 in the calcium group and 423 in the placebo group ) who completed both follow-up examinations . At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group ( 31 percent ) and 159 subjects in the placebo group ( 38 percent ) ; the adjusted risk ratio was 0.81 ( 95 percent confidence interval , 0.67 to 0.99 ; P=0.04 ) . The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 ( 95 percent confidence interval , 0.60 to 0.96 ; P=0.02 ) . The effect of calcium was independent of initial dietary fat and calcium intake . CONCLUSIONS Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas", "CONTEXT AND OBJECTIVE It is not known which factors are associated with fracture in nonosteoporotic elderly . The aim of this study was to assess the association between fall-related risk factors and fracture risk in men and women without osteoporosis . DESIGN This study was part of the ongoing Dubbo Osteoporosis Epidemiology Study , which was design ed as a prospect i ve population -based cohort investigation . PARTICIPANTS At baseline , 924 women and 723 men aged 60 + yr did not have osteoporosis [ bone mineral density ( BMD ) T-scores > -2.5 ] . The individuals have been followed for up to 15 yr . MAIN OUTCOME MEASURES Atraumatic fractures were prospect ively identified through radiologists ' reports . RISK FACTORS At baseline , femoral neck BMD ( FNBMD ) was measured by dual energy x-ray absorptiometry ( DXA ) ; history of fall , postural stability , and quadriceps strength was obtained . RESULTS During the follow-up period , among the nonosteoporotic group , 221 women and 105 men had sustained a fracture , accounting for 55 and 74 % of total fractures in the entire Dubbo Osteoporosis Epidemiology Study sample , respectively . The following factors were independent risk factors for any fracture : in women , age per sd ( hazard ratio , 1.2 ; 95 % CI , 1.0 - 1.3 ) , postural sway per sd ( 1.1 , 1.0 - 1.2 ) , FNBMD per sd ( 1.6 , 1.3 - 1.9 ) , fall in the previous 12 months ( 2.1 , 1.6 - 2.7 ) , and prior fracture ( 1.8 , 1.2 - 2.7 ) ; in men , age ( 1.4 , 1.1 - 1.6 ) , postural sway ( 1.2 , 1.0 - 1.3 ) , FNBMD ( 1.2 , 1.0 - 1.5 ) , and fall in the previous 12 months ( 1.9 , 1.2 - 3.0 ) . Exposure to at least one of the risk factors could account for 49 % ( women ) and 39 % ( men ) of any fractures in this population . CONCLUSION In nonosteoporotic elderly , the combination of low BMD , advancing age , fall during the last 12 months , and prior fracture could identify a subgroup of individuals with high risk of fracture", "The effect of dietary calcium on hip fracture risk was examined prospect ively using the NHANES I Epidemiologic Follow-Up Study cohort , which is derived from a nationally representative sample of the United States population . A cohort of 4342 white men and postmenopausal women ages 50–74 years at baseline ( 1971–1975 ) were observed through 1987 for up to 16 years of follow-up . Quantitative estimates of calcium intake were obtained at baseline from a 24-h recall , while weekly frequency of dairy food consumption was obtained from a qualitative food frequency . By 1987 , 44 men and 122 women had experienced a hip fracture according to hospital records or death certificates . In the total sample of women the risk of hip fracture was only slightly lower for the highest quartile compared with the lowest . However , although not statistically significant , the age-adjusted risk of hip fracture was approximately 50 % lower in the highest quartile of calcium intake compared with the lowest quartile in the subgroup of women who were at least 6 years postmenopausal and not taking postmenopausal hormone . The low relative risk observed among men , although interesting , must be interpreted cautiously due to small sample size . Adjusting for other risk factors did not appreciably change the results for either sex . The pattern of relative risks for calcium quartiles and by selected cutpoints was not consistent with a dose-response effect of calcium . Our results suggest that calcium may lower hip fracture risk in late menopausal women", "Summary The Women 's Health Initiative ( WHI ) double-blind , placebo-controlled clinical trial r and omly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D3 daily or placebo , with average intervention period of 7.0 years . The trial was design ed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture , and secondarily , total fracture and colorectal cancer . Introduction This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data , with emphasis on fractures , cardiovascular disease , cancer , and total mortality . Methods WHI calcium and vitamin D r and omized clinical trial ( CT ) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation , and these data were contrasted and combined with corresponding data from the WHI prospect i ve observational study ( OS ) . Results Among women not taking personal calcium or vitamin D supplements at baseline , the hazard ratio [ HR ] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 ( 95 % confidence interval ( CI ) , 0.38–1.00 ) . In combined analyses of CT and OS data , the corresponding HR was 0.65 ( 95 % CI , 0.44–0.98 ) . Supplementation effects were not apparent on the risks of myocardial infa rct ion , coronary heart disease , total heart disease , stroke , overall cardiovascular disease , colorectal cancer , or total mortality , while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive . Conclusion Though based primarily on a subset analysis , long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women . Other health benefits and risks of supplementation at doses considered , including an elevation in urinary tract stone formation , appear to be modest and approximately balanced", "In a double-blind trial , 327 patients ( 57 men ) over 65 ( mean age 79.5 ) years received all possible combinations of calcium carbonate 3 g , vitamin D3 1000 iu , meth and ienone 2.5 mg and /or placebos daily for 9 months . The higher incidence of bone fractures in the placebo group was not significant . Serum calcium , phosphorus , creatinine , aspartate aminotransferase and alkaline phosphatase were followed : the greatest changes occurred with meth and ienone , which thus reduced osteoporotic activity and increased the muscular mass most effectively ; calcium carbonate had the poorest effect . Surprisingly , coronary mortality was higher among those taking all three active substances . With two treatments the increase was not significant , but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments , a significant increase in coronary deaths was seen , most significant ( P less than 0.001 ) in those receiving vitamin D3 and meth and ienone", "Summary We ascertained the incidence and predictors of radiographic vertebral fracture in a Brazilian elderly cohort , since no data in this field have been reported in low-income countries . This is the first population -based study to demonstrate the high frequency of vertebral fracture in elderly Latin Americans . Age , prior fracture , BMD , and bone turnover were predictors of fracture . Introduction Vertebral fractures are associated with increased future fracture risk and mortality . No data on incidence of osteoporotic vertebral fracture have been reported in low-income countries where the population ’s aging has been faster . Thus , we sought to describe the incidence and risk factors for radiographic vertebral fracture in a longitudinal prospect i ve Brazilian population -based elderly cohort . Methods 707 older adults ( 449 women and 258 men ) were evaluated with spinal radiographs obtained at baseline and after a mean follow-up of 4.3 ± 0.8 years . New vertebral fracture was defined as distinct alteration in the morphology of vertebrae result ing in higher grade of deformity on the second radiograph when compared to the baseline radiograph . Clinical question naire , bone mineral density ( BMD ) , and laboratory tests were performed at baseline . Multivariate Poisson regression models were used to identify independent predictors of fracture . Results The age-st and ardized incidence of vertebral fracture was 40.3/1,000 person-years in women and 30.6/1,000 in men . In women , three models of risk factors for fracture were fitted : ( 1 ) age ( relative risks ( RR ) 2.46 , 95 % confidence interval ( CI ) 1.66–3.65 ) , previous osteoporotic fracture ( RR 1.65 , 95 % CI 1.00–2.71 ) , and lumbar spine BMD ( RR 1.21 , 95 % CI 1.03–1.41 ) ; ( 2 ) age ( RR 2.25 , 95 % CI 1.52–3.34 ) and femoral neck BMD ( RR 1.42 , 95 % CI 1.11–1.81 ) ; ( 3 ) age ( RR 2.11 , 95 % CI 1.41–3.15 ) and total hip BMD ( RR 1.56 , 95 % CI 1.21–2.0 ) . In men , the highest quartile of cross-linked C-telopeptide ( CTx ) ( RR 1.96 , 95 % CI 0.98–3.91 ) and prior fracture ( RR 2.10 , 95 % CI 1.00–4.39 ) were predictors of new vertebral fracture . Conclusions This is the first population -based study to ascertain the incidence of vertebral fracture in elderly Latin Americans , confirming the high frequency of the disorder . Age , prior fracture , BMD , and bone turnover were predictors of the short-term incidence of vertebral fracture", "Background / Objectives : Evidence on the role of diet during adulthood and beyond on fracture occurrence is limited . We investigated diet and hip fracture incidence in a population of elderly Europeans , participants in the European Prospect i ve Investigation into Cancer and nutrition study .Subjects/ Methods : 29 122 volunteers ( 10 538 men , 18 584 women ) aged 60 years and above ( mean age : 64.3 ) from five countries were followed up for a median of 8 years and 275 incident hip fractures ( 222 women and 53 men ) were recorded . Diet was assessed at baseline through vali date d dietary question naires . Data were analyzed through Cox proportional-hazards regression with adjustment for potential confounders . Results : No food group or nutrient was significantly associated with hip fracture occurrence . There were suggestive inverse associations , however , with vegetable consumption ( hazard ratio ( HR ) per increasing sex-specific quintile : 0.93 , 95 % confidence interval ( CI ) : 0.85–1.01 ) , fish consumption ( HR per increasing sex-specific quintile : 0.93 , 95 % CI : 0.85–1.02 ) and polyunsaturated lipid intake ( HR per increasing sex-specific quintile : 0.92 , 95 % CI : 0.82–1.02 ) , whereas saturated lipid intake was positively associated with hip fracture risk ( HR per increasing sex-specific quintile : 1.13 , 95 % CI : 0.99–1.29 ) . Consumption of dairy products did not appear to influence the risk ( HR per increasing sex-specific quintile : 1.02 , 95 % CI : 0.93–1.12 ) . Conclusions : In a prospect i ve study of the elderly , diet , including consumption of dairy products , alcohol and vitamin D , did not appear to play a major role in hip fracture incidence . There is however , weak and statistically non-significant evidence that vegetable and fish consumption and intake of polyunsaturated lipids may have a beneficial , whereas saturated lipid intake a detrimental effect", "Although there is some epidemiologic evidence that soy may reduce risk of osteoporotic fracture in women , it is not known whether this risk reduction also occurs for men . The authors examined gender-specific associations between soy intake and hip fracture risk in the Singapore Chinese Health Study , a prospect i ve cohort of 63,257 Chinese living in Singapore . At recruitment between 1993 and 1998 , each subject was administered a food frequency question naire and questions on medical history and lifestyle factors . As of December 31 , 2006 , 276 incident cases of hip fracture in men and 692 cases in women were identified via linkage with hospital discharge data bases . For both genders , hip fracture risk was positively associated with cigarette smoking and was inversely associated with body mass index . There was a statistically significant association of tofu equivalents , soy protein , and isoflavones with hip fracture risk among women but not among men . Compared with women in the lowest quartile of intakes for tofu equivalents ( Risk levels were comparable across the second , third , and fourth quartiles of soy intake categories", "OBJECTIVE --To determine whether low dietary calcium intake and physical inactivity are risk factors for hip fracture among subjects aged 65 and over . DESIGN --Fifteen year follow up study of a large cohort of r and omly selected elderly people living in the community , who had taken part in the 1973 - 4 survey of the Department of Health and Social Security , and for whom dietary and other data were recorded at initial interview and medical assessment . SETTING --Eight areas in Britain ( Engl and ( five ) , Wales ( one ) , and Scotl and ( two ] . SUBJECTS--1688 Subjects living in the community , of whom 1419 subjects ( 720 men and 699 women ) agreed to participate . 1356 Subjects completed a seven day dietary record and 983 ( 542 men and 441 women ) agreed to be assessed by a geriatrician . RESULTS --Incidence of hip fracture increased with age and was higher in women than men . Comparison with matched controls showed no evidence that the risk of hip fracture was related to calcium intake : the odds ratio for the lowest third of dietary calcium compared with the highest was 0.7 ( 95 % confidence interval 0.1 to 3.9 ) after adjustment for smoking and body mass index . The adjusted odds ratio for the lowest third of outdoor activity compared with the highest was 4.3 ( 0.7 to 26.8 ) , and that for grip strength was 3.9 ( 0.7 to 23.0 ) . CONCLUSIONS --Reduced intake of dietary calcium does not seem to be a risk factor for hip fracture . Further evidence is provided that physical activity in the elderly protects against hip fracture", "IMPORTANCE Calcium intake has been promoted because of its proposed benefit on bone health , particularly among the older population . However , concerns have been raised about the potential adverse effect of high calcium intake on cardiovascular health . OBJECTIVE To investigate whether intake of dietary and supplemental calcium is associated with mortality from total cardiovascular disease ( CVD ) , heart disease , and cerebrovascular diseases . DESIGN AND SETTING Prospect i ve study from 1995 through 1996 in California , Florida , Louisiana , New Jersey , North Carolina , and Pennsylvania and the 2 metropolitan areas of Atlanta , Georgia , and Detroit , Michigan . PARTICIPANTS A total of 388 229 men and women aged 50 to 71 years from the National Institutes of Health-AARP Diet and Health Study . MAIN OUTCOME MEASURES Dietary and supplemental calcium intake was assessed at baseline ( 1995 - 1996 ) . Supplemental calcium intake included calcium from multivitamins and individual calcium supplements . Cardiovascular disease deaths were ascertained using the National Death Index . Multivariate Cox proportional hazards regression models adjusted for demographic , lifestyle , and dietary variables were used to estimate relative risks ( RRs ) and 95 % CIs . RESULTS During a mean of 12 years of follow-up , 7904 and 3874 CVD deaths in men and women , respectively , were identified . Supplements containing calcium were used by 51 % of men and 70 % of women . In men , supplemental calcium intake was associated with an elevated risk of CVD death ( RR>1000 vs 0 mg/d , 1.20 ; 95 % CI , 1.05 - 1.36 ) , more specifically with heart disease death ( RR , 1.19 ; 95 % CI , 1.03 - 1.37 ) but not significantly with cerebrovascular disease death ( RR , 1.14 ; 95 % CI , 0.81 - 1.61 ) . In women , supplemental calcium intake was not associated with CVD death ( RR , 1.06 ; 95 % CI , 0.96 - 1.18 ) , heart disease death ( 1.05 ; 0.93 - 1.18 ) , or cerebrovascular disease death ( 1.08 ; 0.87 - 1.33 ) . Dietary calcium intake was unrelated to CVD death in either men or women . CONCLUSIONS AND RELEVANCE Our findings suggest that high intake of supplemental calcium is associated with an excess risk of CVD death in men but not in women . Additional studies are needed to investigate the effect of supplemental calcium use beyond bone health", "Excess dietary proteins and \" acid ash \" diets have been suspected to increase the risk of osteoporosis , but experimental and epidemiological evidence is mixed . We aim ed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet ( as renal net acid excretion [ RNAE ] estimate ) and fracture risk vary according to calcium intake . During an average of 8.37 + /- 1.73 yr of follow-up , 2408 women reported a fracture ( excluding high-impact trauma ) among 36,217 postmenopausal women from the E3N prospect i ve study . We used Cox regression models to study the interaction between calcium and , respectively , proteins and RNAE , from the 1993 dietary question naire for fracture risk determination , adjusting for potential confounders . There was no overall association between fracture risk and total protein or RNAE . However , in the lowest quartile of calcium ( fracture risk ( RR = 1.51 for highest versus lowest quartile ; 95 % CI , 1.17 - 1.94 ) . An increasing fracture risk with increasing animal protein intake was also observed ( trend , p interaction for fracture risk was observed between RNAE and calcium . In this Western population of postmenopausal women with normal to high protein intake and fairly high calcium intake , there was no overall association between total protein or RNAE and fracture risk . However , there was some evidence that high protein-high acid ash diets were associated with an increased risk of fracture when calcium intake was low ( < 400 mg/1000 kcal )", "Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry", "Dairy foods are rich in bone-beneficial nutrients , yet the role of dairy foods in hip fracture prevention remains controversial . Our objective was to evaluate the association of milk , yogurt , cheese , cream , and milk + yogurt intakes with incident hip fracture in the Framingham Original Cohort . A total of 830 men and women from the Framingham Original Cohort , a prospect i ve cohort study , completed a food-frequency question naire ( 1988 to 1989 ) and were followed for hip fracture until 2008 . In this population -based study , Cox-proportional hazards regression was used to estimate hazard ratios ( HR ) by categories of energy-adjusted dairy intake ( servings/wk ) , adjusting for st and ard confounders and covariates . The exposure was energy-adjusted intakes of milk , yogurt , cheese , cream , and milk + yogurt ( servings/wk ) . Risk of hip fracture over the follow-up was the primary outcome ; the hypothesis being tested was formulated after data collection . The mean age at baseline was 77 years ( SD 4.9 , range 68 to 96 ) . Ninety-seven hip fractures occurred over the mean follow-up time of 11.6 years ( range 0.04 to 21.9 years ) . The mean ± SD ( servings/wk ) of dairy intakes at baseline were : milk = 6.0 ± 6.4 ; yogurt = 0.4 ± 1.3 ; cheese = 2.6 ± 3.1 ; and cream = 3.4 ± 5.5 . Participants with medium ( > 1 and lower hip fracture risk than those with low ( ≤1 serving/wk ) intake ( high versus low intake HR 0.58 , 95 % confidence interval [ CI ] 0.31 - 1.06 , p = 0.078 ; medium versus low intake HR 0.61 , 95 % CI 0.36 - 1.08 , p = 0.071 ; p trend = 0.178 ] . There appeared to be a threshold for milk , with 40 % lower risk of hip fracture among those with medium/high milk intake compared with those with low intake ( p = 0.061 ) . A similar threshold was observed for milk + yogurt intake ( p = 0.104 ) . These associations were further attenuated after adjustment for femoral neck bone mineral density . No significant associations were seen for other dairy foods ( p range = 0.117 to 0.746 ) . These results suggest that greater intakes of milk and milk + yogurt may lower risk for hip fracture in older adults through mechanisms that are partially , but not entirely , attributable to effects on bone mineral density", "Summary Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people . In a r and omised controlled trial , adherence to sunlight exposure was low ( median adherence , 26 % ) and no effect of increased UV exposure on falls risk was observed ( incidence rate ratio ( IRR ) 1.06 , P = 0.73 ) . Introduction This study aim ed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly . Methods In a cluster r and omised controlled trial ( NCT00322166 at Clinical Trials.gov ) , 602 residents aged 70 or more ( mean age , 86.4 years ; 71 % female ) were recruited from 51 aged care facilities in Northern Sydney , Australia . Participants were r and omised by facility to receive either increased sunlight exposure ( additional 30–40 min/day in the early morning ) with ( UV+ ) or without ( UV ) calcium supplementation ( 600 mg/day ) or neither ( control ) for a year . The co- primary endpoints were change in serum 25 hydroxy vitamin D ( 25OHD ) and falls incidence after 12 months . Results Adherence to sunlight exposure was low ( median adherence , 26 % ; IQR , 7%–45 % ) . Serum 25OHD levels were low at baseline ( median , 32.9 nmol/L ) and increased only slightly depending on the number of sunlight sessions attended over 12 months ( P = 0.04 ) . During the study , 327 falls occurred in 111 ( 54 % ) subjects in the control group , 326 falls in 111 ( 58 % ) subjects in the UV only group and 335 falls in 108 ( 52 % ) subjects in the UV+ group . By intention-to-treat analysis , there was no significant effect of increased UV exposure on falls risk ( IRR , 1.06 ; 95 % CI , 0.76–1.48 ; P = 0.73 ) . However , in 66 participants who attended ≥130 sessions per year ( adherence , ≥50 % of 260 sessions – five per week ) , falls were significantly reduced ( IRR , 0.52 ; 95 % CI , 0.31–0.88 ; P = 0.01 ) compared with the control group . Conclusions Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people . This public health strategy was not effective most likely due to poor adherence to the intervention", "UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation", "OBJECTIVE Bone fractures are an important cause of morbidity and mortality among the elderly in the US . The present study assesses the possible role of a number of risk factors for postmenopausal bone fractures . METHODS We analysed the relationships of anthropometric , demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospect i ve cohort study , the New York University Women 's Health Study . RESULTS After an average of 7.6 years of follow-up , 1025 new incident bone fractures were reported , including 34 hip and 159 wrist fractures ( incidence rates ; 71.6 and 334.7 per 105 woman-years , respectively ) . The risk of fracture increased with increasing age , body height and total fat intake , while it was significantly lower among obese and African American women . The relative risk among African Americans was 0.45 ( 95 % CI : 0.32 - 0.63 ) compared with non-African Americans . Women taller than 170 cm had a 64 % increase in risk of fractures , as compared with those under 155 cm . These associations were generally more pronounced when fractures were limited to those at the hip and wrist . CONCLUSIONS The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity , short stature and African American ethnicity", "Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures . A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites , bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a r and omized , double-blind , placebo-controlled trial . Bone mineral density ( BMD ) was measured by dual x-ray absorptiometry and bone structure by radiographs . Calcium biochemistry and bone turnover markers were measured in blood and urine . The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr . Baseline median calcium intake was 546 mg/day , and median serum 25OH vitamin D3 was 59 nmol/L. On placebo , loss of BMD at total hip was 2 % and femoral medulla expansion was 3 % over 4 yr . Calcium reduced bone loss , secondary hyperparathyroidism , and bone turnover . 25OH vitamin D3 was intermediate between placebo and calcium . Fracture rates and drop-out rates were similar among groups , and there were no serious adverse events with either supplement . A calcium supplement of 750 mg/day prevents loss of BMD , reduces femoral medullary expansion , secondary hyperparathyroidism , and high bone turnover . A supplement of 15 microg/day 25OH vitamin D3 is less effective , and because its effects are seen only at low calcium intakes , suggests that its beneficial effect is to reverse calcium insufficiency", "OBJECTIVE The risk factors for fractures are incompletely understood . An outst and ing question concerns the optimal amount of dietary calcium needed to minimise the risk of fracture . DESIGN We examined the associations of dietary calcium and other nutrients with self-reported fracture risk in a prospect i ve cohort study . Nutrient intakes were estimated using a semi-quantitative food-frequency question naire administered at recruitment . SETTING The UK . PARTICIPANTS A total of 26 749 women and 7947 men aged 20 - 89 years . RESULTS Over an average of 5.2 years of follow-up , 1555 women and 343 men reported one or more fractures , 72 % of these result ing from a fall . Among women , fracture risk was higher at lower calcium intakes , with a relative risk of 1.75 ( 95 % confidence interval ( CI ) 1.33 - 2.29 ) among women with a calcium intake of dietary calcium with fracture risk was stronger among women aged under 50 years at recruitment than among women aged 50 and above . Dietary calcium intake was not associated with fracture risk in men . Fracture risk was not related to the dietary intake of any other nutrient examined . CONCLUSION In this population , women with a low dietary calcium intake had an increased risk of bone fracture , and this association was more marked among younger women than among older women", "Abstract : Elderly women with very low bone mineral density ( BMD ) ( T-score ≤−3.5 ) have a risk of hip fracture more than two times higher than the average risk of women of the same age . Using data from the EPIDOS prospect i ve study , we have shown that by measuring BMD on the 50 % of women who have the lowest weight , it is possible to identify the majority of these women at higher risk . In the present analysis , we assessed whether the use of clinical risk factors , in the subset of women selected for osteodensitometry and with moderately low BMD ( T-score between −3.5 and −2.5 ) , allows the identification of another subgroup of women with a risk 2 times higher than average and , thereby , increases the efficiency of selective BMD screening . We then assessed the discriminant value for hip fracture of the overall screening strategy ( i.e. , use of weight to select women for osteodensitometry , then use of clinical risk factors to enhance the predictive value of BMD ) , and compared it with the value of BMD used as a population screening tool . In total , 6933 EPIDOS participants , aged 75 years or above , were included in this analysis . Using Cox regression models , we first determined which baseline factors were most predictive of hip fracture among the 1588 women with weight below median ( selection criteria for osteodensitometry in the proposed strategy ) and T-score between −3.5 and −2.5 . Based on the relative risk ( RR ) estimates from the final risk function , we calculated an individual risk score for hip fracture . We assessed the incidence of hip fracture for each value of the score , and determined the cutoff to identify women with a risk about 2 times higher than the average risk in this elderly cohort . The overall screening strategy ( i.e. , selective BMD measurement based on weight , followed by clinical fracture risk assessment ) identifies two subgroups of higher risk women : a group with very low BMD ( T-score ≤–3.5 ) , and another group with moderately low BMD ( T-score between –3.5 and –2.5 ) but a high fracture risk score . We calculated the total number of women classified as being at high risk , and assessed the overall sensitivity and specificity of this strategy to identify elderly women who will suffer a hip fracture . Among women with weight below median and T-score between −3.5 and −2.5 , the factors most predictive of the risk of hip fracture were age , history of fall , ability to do the t and em walk ( test of dynamic balance ) , gait speed and visual acuity . A simple additive score based on these factors ( except visual acuity ) allows a high-risk group ( risk about 2 times higher than average ) to be clearly distinguished from a low-risk group ( risk below average ) . Overall , the proposed strategy identifies approximately 15 % of the women in the cohort as being at high risk , i.e. , 543 women with T-score ≤−3.5 and 503 women with −3.5 and a high fracture risk score . The sensitivity for hip fracture is equal to 37 % and the specificity to 85 % , which is equivalent to the discriminant value of BMD as a population screening tool . In elderly women , the use of a simple clinical risk score , in women with previous BMD values , allows the number of high-risk women identified to be increased . Overall , the proposed screening strategy ( use of weight to select women for osteodensitometry , and then use of clinical risk factors to enhance the predictive value of BMD ) has the same discriminant value for hip fracture as BMD used as a population screening tool", "Abstract : This prospect i ve population -based cohort study investigated factors predicting distal forearm fracture ( DFF ) in perimenopausal women . The study population consisted of 11 798 women from the Kuopio Osteoporosis Risk Factor and Prevention ( OSTPRE ) Study in Finl and . Mean baseline age of these women was 52.3 ( SD 2.9 ) years ( range 47–56 years ) and 68 % were postmenopausal . Three hundred and sixty-eight women ( 3.1 % ) had a vali date d DFF during the 5-year follow-up . Previous wrist fracture , postmenopausal state , age and Noneiparity were independent predictors of DFF , while hormone replacement therapy ( HRT ) , dairy calcium and overweight protected against it in multivariate Cox regression analysis : previous wrist fracture increased the DFF risk by 158 % ( p menopause by 69 % ( p= 0.002 ) and age by 6 % per year ( p= 0.010 ) , whereas the continuous use of HRT decreased the risk by 63 % ( p= 0.0001 ) , the use of dairy calcium at 1000–1499 mg/day ( vs 25 kg/m2 ) by 36 % ( p= 0.0002 ) and parity by 29 % ( p= 0.031 ) . Combining dichotomous low weight , low use of calcium , non-use of HRT and previous wrist fracture into a risk score gave a dose – response effect by score level : the presence ( vs absence ) of all four risk factors result ed in a 12-fold DFF risk . Nevertheless , the sensitivity and specificity of the score for detecting DFF remained low . It was concluded that HRT , high nutritional calcium intake and overweight protect against but a history of wrist fracture predisposes to perimenopausal distal forearm fracture . A simple risk factor inquiry would help to identify perimenopausal women at high risk of distal forearm fracture", "We tested the spine antifracture and bone sparing efficacy of 1.2 g/day of oral calcium as carbonate in two groups of elderly women , one with prevalent fractures ( PF , n = 94 ) on entry and the other without ( NPF , n = 103 ) . It was a prospect i ve r and omized , double-blind , placebo-controlled trial in mostly rural communities in women over age 60 who were living independently and were consuming calcium . We obtained annual lateral spine radiographs and semiannual forearm bone density over 4.3 + /- 1.1 years and determined vertebral fractures by radiographic morphometry augmented by physician assessment . In the PF group , 15 of 53 subjects on calcium had incident fractures , compared with 21 of 41 on placebo ( p = 0.023 , chi2 ) . Calcium did not reduce the rate of incident fractures in the NPF group . Those with a prevalent fracture on entry and not treated with calcium were 2.8 times more likely to experience an incident fracture than all others . Change in the forearm bone mass on placebo in the PF group was -1.24 + /- 2.41%/year compared with + 0.31 + /- 1.80%/year on calcium ( p elderly postmenopausal women with spine fractures and selfselected calcium intakes of , a calcium supplement of 1.2 g/day reduces the incidence of spine fractures and halts measurable bone loss", "This study was design ed to identify independent predictors of all osteoporosis-related fractures ( ORFs ) among healthy Saudi postmenopausal women . We prospect ively followed a cohort of 707 healthy postmenopausal women ( mean age , 61.3±7.2 years ) for 5.2±1.3 years . Data were collected on demographic characteristics , medical history , personal and family history of fractures , lifestyle factors , daily calcium intake , vitamin D supplementation , and physical activity score . Anthropometric parameters , total fractures ( 30.01 per 1000 women/year ) , special physical performance tests , bone turnover markers , hormone levels , and bone mineral density ( BMD ) measurements were performed . The final model consisted of seven independent predictors of ORFs : [ lowest quartile ( Q(1 ) ) vs highest quartile ( Q(4 ) ) ] physical activity score ( Q(1 ) vs Q(4 ) : ≤12.61 vs ≥15.38 ) ; relative risk estimate [ RR ] , 2.87 ; ( 95 % confidence interval [ CI ] : 1.88 - 4.38 ) ; age≥60 years vs age ) ; h and grip strength ( Q(1 ) vs Q(4 ) : ≤13.88 vs ≥17.28 kg ) ( RR=1.88 ; 95 % CI : 1.15 - 3.05 ) ; BMD total hip ( Q(1 ) vs Q(4 ) : ≤0.784 vs 0.973 g/cm(2 ) ) ( RR=1.86 ; 95 % CI : 1.26 - 2.75 ) ; dietary calcium intake ( Q(1 ) vs Q(4 ) : ≤391 vs ≥648 mg/day ) ( RR=1.66 ; 95 % CI : 1.08 - 2.53 ) ; serum 25(OH)D ( Q(1 ) vs Q(4 ) : ≤17.9 vs ≥45.1 nmol/L ) ( RR=1.63 ; 95 % CI : 1.06 - 2.51 ) ; and past year history of falls ( RR=1.61 ; 95 % CI : 1.06 - 2.48 ) . Compared with having none ( 41.9 % of women ) , having three or more clinical risk factors ( 4.8 % of women ) increased fracture risk by more than 4-fold , independent of BMD . Having three or more risk factors and being in the lowest tertile of T-score of [ total hip/lumbar spine ( L1-L4 ) ] was associated with a 14.2-fold greater risk than having no risk factors and being in the highest T-score tertile . Several clinical risk factors were independently associated with all ORFs in healthy Saudi postmenopausal women . The combination of multiple clinical risk factors and low BMD is a very powerful indicator of fracture risk", "As part of a prospect i ve study begun in 1981 , we evaluated 8,600 postmenopausal women and 5,049 men residing in a southern California retirement community for risk factors for hip fracture . Incidence rates were twice as high in women as in men , but in both sexes the rates nearly doubled every 5 years between 70 and 90 years . Active exercise was strongly and negatively associated with hip fracture risk in both sexes ; the age-adjusted relative risk was 0.6 and 0.5 for females and males , respectively , for 1 or more hours of exercise per day compared with less than 1/2 hour of exercise . A high body mass index ( upper tertile of weight divided by height squared ) was associated with a strong reduction in hip fracture risk for females ( RR = 0.5 ) . Current cigarette smokers had a significantly increased risk ( RR = 1.8 and RR = 2.2 for females and males , respectively ) compared with never-smokers , but the risk for past smokers was not different from that of lifetime nonsmokers . Other factors related to reduced hip fracture risk in women were high parity , late age at menarche , and long menstrual cycle length . These age-adjusted relative risk estimates did not change material ly in multivariate analysis when adjusted simultaneously for age , active exercise , body mass , smoking , and , for women , age at menarche and number of children . Among estrogen users , the lowest risk of hip fracture was observed for recent users ( RR = 0.8 ) , while users who had stopped estrogen use 15 or more years ago had a relative risk of 1.1 , suggesting that the protective effect of estrogen dissipates after many years since cessation of estrogen", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "This prospect i ve population -based study assessed predictors of hip fracture risk in white men . Participants were members of the Epidemiologic Follow-up Study cohort of the First National Health and Nutrition Examination Survey , a nationally representative sample of noninstitutionalized civilians who were followed for a maximum of 22 years . A cohort of 2879 white men ( 2249 in the nutrition and weight-loss sub sample , 1437 in the bone density sub sample ) aged 45 - 74 years at baseline ( 1971 - 1975 ) were observed through 1992 . Ninety-four percent of the original cohort were successfully traced . Hospital records and death certificates were used to identify a total of 71 hip fracture cases ( 61 in the nutrition and weight-loss sub sample , 26 in the bone-density sub sample ) . Among the factors evaluated were age at baseline , previous fractures other than hip , body mass index , smoking status , alcohol consumption , nonrecreational physical activity , weight loss from maximum , calcium intake , number of calories , protein consumption , chronic disease prevalence , and phalangeal bone density . The risk adjusted relative risk ( RR ) of hip fracture was significantly associated with presence of one or more chronic conditions ( RR = 1.91 , 95 % confidence interval [ CI ] = 1.19 - 3.06 ) , weight loss from maximum > or = 10 % ( RR = 2.27 , 95 % CI 1.13 - 4.59 ) , and 1 SD change in phalangeal bone density ( RR = 1.73 , 95 % CI 1.11 - 2.68 ) . No other variables were significantly related to hip fracture risk . Although based on a small number of cases , this is one of the first prospect i ve studies to relate weight loss and bone density to hip fracture risk in men", "Most reported associations in observational clinical research are false , and the minority of associations that are true are often exaggerated . This credibility problem has many causes , including the failure of authors , review ers , and editors to recognize the inherent limitations of these studies . This issue is especially problematic for weak associations , variably defined as relative risks ( RRs ) or odds ratios ( ORs ) less than 4 . Such associations , commonly reported in the medical literature , are more likely to be attributable to bias than to causal association . All observational research has bias ( which can include selection , information , and confounding bias ) . Hence , detection of small associations falls below the discriminatory ability of observational studies . In general , unless RRs in cohort studies exceed 2 to 3 or ORs in case-control studies exceed 3 or 4 , associations in observational research findings should not be considered credible . However , these guidelines are not foolproof : strong ( yet spurious ) associations can result when large amounts of bias are present . Only in a properly performed r and omized controlled trial , free of bias , should small associations merit attention . Better training and more circumspection on the part of investigators , tougher editorial st and ards on the part of journals , and hefty skepticism on the part of referees and readers are necessary to avoid the dangers of false alarms , pseudo-epidemics , and their unfortunate consequences", "UNLABELLED We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years . Six clinical risk factors predicted fracture risk independent of hip BMD : tricyclic antidepressant use , previous fracture , inability to complete a narrow walk trial , falls in previous year , age > or = 80 years , and depressed mood . INTRODUCTION There are few prospect i ve studies of fracture determinants in men . We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD . MATERIAL S AND METHODS A total of 5995 men > or = 65 years of age were recruited from six communities in the Unites States and followed prospect ively for an average of 4.1 years . Baseline assessment s of demographic , lifestyle , medical history , functional status , anthropometry , and cognitive , visual , and neuromuscular function were assessed by question naire or examination . Triannual mailed question naires ascertained incident fracture ; reported fractures were adjudicated by physicians using medical records and X-ray reports . Proportional hazards models were used to develop multivariable models , selecting variables and controlling for BMD . RESULTS Of 5876 men , 4.7 % ( N = 275 ) reported an incident nonspine fracture during follow-up ( 11.46/1000 person-years ) . Tricyclic antidepressant use ( hazard ratio [ HR ] , 2.36 ; 95 % CI , 1.25 - 4.46 ) , history of fracture at or after age 50 ( HR , 2.07 ; 95 % CI , 1.62 - 2.65 ) , inability to complete a narrow walk trial ( HR , 1.70 ; 95 % CI , 1.23 - 2.34 ) , falls in previous year ( HR , 1.59 ; 95 % CI , 1.23 - 2.05 ) , age > or = 80 years ( HR , 1.33 ; 95 % CI , 1.01 - 1.76 ) , depressed mood ( HR , 1.72 ; 95 % CI , 1.00 - 2.95 ) , and decreased total hip BMD ( HR , 1.53 ; 95 % CI , 1.34 - 1.74 ) were independently related to increased risk . Compared with having none ( 48.0 % of men ) , having three or more of the clinical risk factors ( 4.9 % of men ) increased fracture risk 5-fold , independent of BMD . Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile . CONCLUSIONS Several clinical risk factors were independently associated with nonspine fractures in elderly men . The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk", "BACKGROUND Data on the influence of gonadal hormones on incident fracture risk in elderly men are limited . We prospect ively examined the relationship between serum levels of testosterone and estradiol and future fracture risk in community-dwelling men . METHODS A total of 609 men older than 60 years had been observed between January 1989 and December 2005 , with the median duration being 5.8 years ( up to 13 years ) . Clinical risk factors , including bone mineral density and lifestyle factors , were assessed at baseline . Serum testosterone and estradiol levels were measured by t and em mass spectrometry . The incidence of a low-trauma fracture was ascertained during follow-up . RESULTS During follow-up , 113 men had at least 1 low-trauma fracture . The risk of fracture was significantly increased in men with reduced testosterone levels ( hazard ratio [ HR ] , 1.33 ; 95 % confidence interval [ CI ] , 1.09 - 1.62 ) . After adjustment for sex hormone-binding globulin , serum testosterone ( HR , 1.48 ; 95 % CI , 1.22 - 1.78 ) and serum estradiol ( HR , 1.21 ; 95 % CI , 1.00 - 1.47 ) levels were associated with overall fracture risk . After further adjustment for major risk factors of fractures ( age , weight or bone mineral density , fracture history , smoking status , calcium intake , and sex hormone-binding globulin ) , lower testosterone was still associated with increased risk of fracture , particularly with hip ( HR , 1.88 ; 95 % CI , 1.24 - 2.82 ) and nonvertebral ( HR , 1.32 ; 95 % CI , 1.03 - 1.68 ) fractures . CONCLUSION In community-dwelling men older than 60 years , serum testosterone is independently associated with the risk of osteoporotic fracture and its measurement may provide additional clinical information for the assessment of fracture risk in elderly men", "Objective To determine the effect of calcium supplementation on myocardial infa rct ion , stroke , and sudden death in healthy postmenopausal women . Design R and omised , placebo controlled trial . Setting Academic medical centre in an urban setting in New Zeal and . Participants 1471 postmenopausal women ( mean age 74 ) : 732 were r and omised to calcium supplementation and 739 to placebo . Main outcome measures Adverse cardiovascular events over five years : death , sudden death , myocardial infa rct ion , angina , other chest pain , stroke , transient ischaemic attack , and a composite end point of myocardial infa rct ion , stroke , or sudden death . Results Myocardial infa rct ion was more commonly reported in the calcium group than in the placebo group ( 45 events in 31 women v 19 events in 14 women , P=0.01 ) . The composite end point of myocardial infa rct ion , stroke , or sudden death was also more common in the calcium group ( 101 events in 69 women v 54 events in 42 women , P=0.008 ) . After adjudication myocardial infa rct ion remained more common in the calcium group ( 24 events in 21 women v 10 events in 10 women , relative risk 2.12 , 95 % confidence interval 1.01 to 4.47 ) . For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group ( relative risk 1.47 , 0.97 to 2.23 ) . When unreported events were added from the national data base of hospital admissions in New Zeal and the relative risk of myocardial infa rct ion was 1.49 ( 0.86 to 2.57 ) and that of the composite end point was 1.21 ( 0.84 to 1.74 ) . The respective rate ratios were 1.67 ( 95 % confidence intervals 0.98 to 2.87 ) and 1.43 ( 1.01 to 2.04 ) ; event rates : placebo 16.3/1000 person years , calcium 23.3/1000 person years . For stroke ( including unreported events ) the relative risk was 1.37 ( 0.83 to 2.28 ) and the rate ratio was 1.45 ( 0.88 to 2.49 ) . Conclusion Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates . This potentially detrimental effect should be balanced against the likely benefits of calcium on bone . Trial registration Australian Clinical Trials Registry ACTRN 012605000242628", "Background Despite the availability of effective preventive and curative medications for osteoporosis , and guidelines for its diagnosis and management , few individuals are treated for osteoporosis , even among those who have already had a fracture . Objectives Our objective was to describe the patterns of use of medication for osteoporosis , i.e. , calcium supplements , vitamin D supplements , and specific anti-osteoporotic drugs , such as bisphosphonates , in a large sample of French older women living at home , and to identify individual factors associated with use of these medications overall and in two specific clinical situations . Methods Cross-sectional analysis of data from 4,221 women aged 75–85 years who participated in a balance and mobility examination as part of the screening procedure for the Ossébo study , a r and omized controlled trial testing the effectiveness of exercise for the prevention of fall-related injuries . Electoral rolls were used to invite women in 16 towns to participate ( participation rate 10.3 % ) . Information collected through question naires included current medication use and , in particular , use of osteoporosis medications ( specific osteoporosis drugs , calcium and vitamin D supplementation ) in the past 6 months , and history of fracture since the age of 50 , including fracture locations . Fractures were categorized in three groups : no fracture , major osteoporotic fracture ( hip , humerus , wrist , pelvis , and vertebra ) , and other fracture . Results Nearly 48 % of the participants reported they did not take calcium or vitamin D supplements or any specific osteoporosis drugs . Of the 2,133 women who reported using osteoporosis medication , 85 % used vitamin D supplements ( 25 % as the sole medication against this disease ) , 59 % calcium supplements , and 42 % a specific anti-osteoporotic drug ( 75 % of them combining it with vitamin D supplementation ) . The use of any osteoporosis medication was significantly associated ( p major osteoporotic fracture , lower weight , dual-energy X-ray absorptiometry ( DXA ) bone-density measurement in the past 5 years , a cancer-screening examination in the past 5 years , and a positive attitude toward medication use in general . Living alone was associated with a lower likelihood of using a specific anti-osteoporotic drug , and a higher education level was associated with a higher likelihood of vitamin D supplementation . Of the 1,553 women who had already had a major osteoporotic fracture , one-third ( 34.8 % ) were not taking any osteoporosis medication . In this subgroup , use of this medication was associated with the same factors as in the overall study population . In particular , neither older age nor a history of falls in the previous 12 months was associated with a higher likelihood of using osteoporosis medication . Among the 909 women who reported using a specific osteoporosis drug , vitamin D use was associated with a higher educational level and a more frequent preventive attitude . Conclusion In France , as in other western countries , women aged 75 years and over are not managed according to guidelines . Further studies should address the barriers encountered in improving quality of care in osteoporosis management", "UNLABELLED Independent risk factors for osteoporotic fracture were identified for a Southern Chinese postmenopausal population . Clinical risk factor assessment with or without BMD measurement was shown to be an effective predictor of 10-yr risk of osteoporotic fracture and provides a more accessible tool for patient evaluation . INTRODUCTION Asian-specific data on risk factors for osteoporosis remain sparse . However , risk factor assessment , in addition to BMD measurement , is increasingly recognized as a reliable predictor of absolute osteoporotic fracture risk . The purpose of this prospect i ve study was to determine the specific independent risk factors for osteoporotic fracture and to predict the 10-yr risk of osteoporotic fracture in the postmenopausal Southern Chinese population . MATERIAL S AND METHODS A total of 1435 community-dwelling , postmenopausal , treatment-naive women were recruited . Baseline demographic characteristics and clinical risk factors were obtained , and BMD at the spine and hip was measured . Subjects were followed for outcomes of incident low trauma fracture . Ten-year risk of osteoporotic fracture was predicted from the risk factor assessment and BMD measurement by Cox proportional hazards models . RESULTS The mean age of subjects was 63.4 + /- 8.3 yr . After 5.0 + /- 2.3 yr ( range , 1.0 - 11.0 yr ) of follow-up , 80 nontraumatic new fractures were reported during follow-up . Eight independent clinical risk factors identified at baseline were found to be significant predictors of osteoporotic fracture , with the most important being use of walking aids ( RR , 4.2 ; 95 % CI , 2.7 - 6.7 ; p history of fall ( RR , 4.0 ; 95 % CI , 2.5 - 6.2 ; p 65 yr , history of fracture , and BMI predicted 10-year risk of osteoporotic fracture of 25 % , which increased to 30 % if they also had total hip BMD T-score Clinical risk factor assessment , with or without BMD measurement , is a reliable predictor of 10-year risk of osteoporotic fracture and may be particularly useful in regions or primary care clinics without access to bone densitometry equipment", "The efficacy of calcium ( Ca ) in reducing bone loss is debated . In a r and omized placebo-controlled double-masked study , we investigated the effects of oral Ca supplements on femoral shaft ( FS ) , femoral neck ( FN ) and lumbar spine ( LS ) bone mineral density ( BMD ) , and on the incidence of vertebral fracture in vitamin-D-replete elderly . Ninety-three healthy subjects ( 72.1±0.6 years ) were r and omly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months . Sixty-three patients ( 78.4±1.0 years ) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo . FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group ( + 0.6±0.5 % v −1.2±0.7%,p of Ca . The changes of + 0.7±0.8 % v −1.7±1.6 % in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance . In fractured patients , FS , FN and LS BMD changes were −1.3±0.8 , + 0.3±1.6 and + 3.1±1.2 % ( p . The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group , respectively , and 144.0 in Ca-supplemented fractured patients . Thus , oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly", "Abstract : This prospect i ve study was aim ed at determining the risk factors for the development of fractures in perimenopausal women . The study group ( n= 3068 ) was comprised of a stratified population sample of women aged between 47 and 56 years . During the follow-up period of 3.6 years , 257 ( 8.4 % ) of the women sustained a total of 295 fractures . After adjustment for covariates , the relative risk ( RR ) of sustaining a fracture was found to be 1.4 [ 95 % confidence interval ( CI ) 1.2–1.6 ] for a 1 st and ard deviation ( SD ) decrease in the spinal and femoral neck bone mineral density ( BMD ) . Women with a previous fracture history were found to have an increased risk of fracture [ RR 1.7 ( 95 % CI 1.3–2.2 ) ] and those reporting three or more chronic illnesses exhibited a RR of 1.4 ( 95 % CI 1.0–1.9 ) . Women not using hormone replacement therapy ( HRT ) had a RR of 1.5 ( 95 % CI 1.1–2.2 ) for all fracture types . When osteoporotic fractures ( vertebral , hip , proximal humerus and wrist fractures ; n= 98 ) were used as an endpoint , the independent risk factors were found to be a low BMD ( RR for a 1 SD decrease in both spinal and femoral neck BMD was 1.6 , 95 % CI 1.3–2.0 ) , a previous fracture history ( RR 1.9 , 95 % CI 1.3–2.9 ) and nonuse of HRT ( RR 2.2 , 95 % CI 1.3–4.0 ) . The independent risk factors for all other fractures ( n = 158 ) were a low BMD ( RR for a 1 SD decrease in the spinal BMD was 1.4 , 95 % CI 1.2–1.6 and in the femoral neck BMD was 1.3 , 95 % CI 1.1–1.5 ) , a previous fracture history ( RR 1.6 , 95 % CI 1.1–2.2 ) , smoking ( RR 1.8 , 95 % CI 1.1–2.7 ) and having had three or more chronic illnesses ( RR 1.6 , 95 % CI 1.1–2.2 ) . Weight , height , age , menopausal status , maternal hip fracture , use of alcohol , coffee consumption or dietary calcium intake were not independently associated with the development of any particular type of fracture . We conclude that the independent risk factors for perimenopausal fractures are a low bone density , previous fracture history , nonuse of HRT , having had three or more chronic illnesses and smoking , the gradient of risk being similar for spinal and femoral neck BMD measurements in the perimenopausal population . The risk factors are slightly different for perimenopausal osteoporotic than for other types of fractures", "BACKGROUND The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day . However , the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known . METHODS We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day . The women were r and omly assigned to treatment with either calcium ( 1000 mg per day ) or placebo for two years . The bone mineral density of the total body , lumbar spine , and proximal femur was measured every six months by dual-energy x-ray absorptiometry . Serum and urine indexes of calcium metabolism were measured at base line and after 3 , 12 , and 24 months . RESULTS The mean ( + /- SE ) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group ( -0.0055 + /- 0.0010 g per square centimeter per year ) as compared with the placebo group ( -0.0097 + /- 0.0010 g per square centimeter per year , P = 0.005 ) . The rate of loss of bone mineral density was reduced by 35 percent in the legs ( P = 0.02 ) , and loss was eliminated in the trunk ( P = 0.04 ) . Calcium use was of significant benefit in the lumbar spine ( P = 0.04 ) , and in Ward 's triangle the rate of loss was reduced by 67 percent ( P = 0.04 ) . Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group . Serum parathyroid hormone concentrations tended to be lower in the calcium group , as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations . CONCLUSIONS Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women", "BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons . Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women", "BACKGROUND Increased dietary calcium intake has been proposed as a population -based public health intervention to prevent osteoporotic fractures . We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action . METHODS Five-year , double-blind , placebo-controlled study of 1460 women recruited from the population and older than 70 years ( mean age , 75 years ) who were r and omized to receive calcium carbonate , 600 mg twice per day , or identical placebo . The primary end points included clinical incident osteoporotic fractures , vertebral deformity , and adverse events ascertained in 5 years . Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body , quantitative ultrasonography of the heel , and peripheral quantitative computed tomography of the distal radius . RESULTS Among our patients , 16.1 % sustained 1 or more clinical osteoporotic fractures . In the intention-to-treat analysis , calcium supplementation did not significantly reduce fracture risk ( hazard ratio , 0.87 ; 95 % confidence interval , 0.67 - 1.12 ) . However , 830 patients ( 56.8 % ) who took 80 % or more of their tablets ( calcium or placebo ) per year had reduced fracture incidence in the calcium compared with the placebo groups ( 10.2 % vs 15.4 % ; hazard ratio , 0.66 ; 95 % confidence interval , 0.45 - 0.97 ) . Calcium-treated patients had improved quantitative ultrasonography findings of the heel , femoral neck and whole-body dual x-ray absorptiometry data , and bone strength compared with placebo-treated patients . Of the 92 000 adverse events recorded , constipation was the only event increased by the treatment ( calcium group , 13.4 % ; placebo group , 9.1 % ) . CONCLUSION Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance , but it is effective in those patients who are compliant", "UNLABELLED To identify risk factors for fractures in multi-ethnic women , we studied 159,579 women enrolled in the Women 's Health Initiative . In general , risk factors for fractures were similar across ethnic groups . However , irrespective of their ethnicity , women with multiple risk factors have a high risk of fracture . Targeting these high-risk women for screening and intervention could reduce fractures . INTRODUCTION Fracture rates tend to be lower in minority women , but consequences may be greater . In addition , the number of fractures is expected to increase in minority women because of current demographic trends . There are limited prospect i ve data on risk factors for fractures in minority women . MATERIAL S AND METHODS We studied 159,579 women 50 - 79 yr of age enrolled in the Women 's Health Initiative . Information on risk factors was obtained by question naire or examination . Nonspine fractures that occurred after study entry were identified over an average follow-up of 8 + /- 2.6 ( SD ) yr . RESULTS Annualized rates ( % ) of fracture in whites , blacks , Hispanics , Asians , and American Indians were 2.0 , 0.9 , 1.3 , 1.2 , and 2.0 , respectively . Significant predictors [ HR ( 95 % CI ) ] of fractures by ethnic group were as follows : blacks : at least a high school education , 1.22 ( 1.0 , 1.5 ) ; ( + ) fracture history , 1.7 ( 1.4 , 2.2 ) ; and more than two falls , 1.7 ( 1.9 , 2.0 ) ; Hispanics : height ( > 162 cm ) , 1.6 ( 1.1 , 2.2 ) ; ( + ) fracture history , 1.9 ( 1.4 , 2.5 ) ; more than two falls , 1.8 ( 1.4 , 2.3 ) ; arthritis , 1.3 ( 1.1 , 1.6 ) ; corticosteroid use , 3.9 ( 1.9 , 8.0 ) ; and parental history of fracture , 1.3 ( 1.0 , 1.6 ) ; Asians : age ( per 5 yr ) , 1.2 ( 1.0 , 1.3 ) ; ( + ) fracture history , 1.5 ( 1.1 , 2.0 ) ; current hormone therapy ( HT ) , 0.7 ( 0.5 , 0.8 ) ; parity ( at least five ) , 1.8 ( 1.1 , 3.0 ) ; more than two falls , 1.4 ( 1.1 , 1.9 ) ; American Indian : ( + ) fracture history , 2 . 9 ( 1.5 , 5.7 ) ; current HT , 0.5 ( 0.3 , 0.9 ) . Women with eight or more risk factors had more than a 2-fold higher rate of fracture compared with women with four or fewer risk factors . Two ethnicity x risk factor interactions were identified : age and fall history . CONCLUSIONS Irrespective of their ethnicity , women with multiple risk factors have a high risk of fracture . Targeting these high-risk women for screening and intervention could reduce fractures", "Antifracture efficacy of high-dose vitamin D ( 800 IU ) and calcium ( 1000 mg ) remains controversial . To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures , we r and omized 3432 women of the population -based Osteoporosis Risk Factor and Prevention ( OSTPRE ) Study cohort ( ages 65 to 71 years ) living in the region of northern Savonia , Finl and ( latitude 62 degrees to 64 degrees N ) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo . The main outcome measure was incident fractures . Fracture data were collected in telephone interviews and vali date d. Data on 3195 women , 1586 in the intervention group and 1609 in the control group , were available for analysis . In adjusted Cox proportional hazards models , the risk of any fracture decreased in the vitamin D and calcium group by 17 % [ adjusted hazard ratio ( aHR ) = 0.83 ; 95 % confidence interval ( CI ) 0.61 - 1.12 ] , and the risk of any nonvertebral fracture decreased by 13 % ( aHR = 0.87 ; 95 % CI 0.63 - 1.19 ) . The risk of distal forearm fractures decreased by 30 % ( aHR = 0.70 ; 95 % CI 0.41 - 1.20 ) , and the risk of any upper extremity fractures decreased by 25 % ( aHR = 0.75 ; 95 % CI 0.49 - 1.16 ) , whereas the risk of lower extremity fractures remained essentially equal ( aHR = 1.02 ; 95 % CI 0.58 - 1.80 ) . None of these effects reached statistical significance . In conclusion , this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65- to 71-year-old general population of postmenopausal women", "Objective This study aims to test the added value of calcium and vitamin D ( CaD ) in fracture prevention among women taking postmenopausal hormone therapy ( HT ) . Methods This is a prospect i ve , partial-factorial , r and omized , controlled , double-blind trial among Women ’s Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years . A total of 27,347 women were r and omized to HT ( 0.625 mg of conjugated estrogens alone , or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily ) , and 36,282 women were r and omized to 1,000 mg of elemental calcium ( carbonate ) plus 400 IU of vitamin D3 daily , each compared with placebo . A total of 16,089 women participated in both arms . The predefined outcomes were adjudicated hip fractures and measured bone mineral density . Results Interaction between HT and CaD on hip fracture ( P interaction = 0.01 ) was shown . The effect of CaD was stronger among women assigned to HT ( hazard ratio [ HR ] , 0.59 ; 95 % CI , 0.38 - 0.93 ) than among women assigned to placebo ( HR , 1.20 ; 95 % CI , 0.85 - 1.69 ) . The effect of HT on hip fracture was stronger among women assigned to active CaD ( HR , 0.43 ; 95 % CI , 0.28 - 0.66 ) than among women assigned to placebo ( HR , 0.87 ; 95 % CI , 0.60 - 1.26 ) . CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake . There was no interaction between HT and CaD on change in hip or spine bone mineral density . Conclusions Postmenopausal women at normal risk for hip fracture who are on CaD supplementation experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake", "We assessed the rates of vertebral fracture in patients with postmenopausal osteoporosis . Forty-five patients were not treated ( 91 person-years of observation ) ; 59 were treated conventionally , with calcium ( alone or combined with estrogen ) or vitamin D or both ( 218 years ) ; and 61 were treated with sodium fluoride combined with conventional therapy ( 251 years ) . The fracture rate ( per thous and person-years ) was 834 in untreated patients , 419 in those given calcium with or without vitamin D , 304 in those given fluoride and calcium with or without vitamin D , 181 in those given estrogen and calcium with or without vitamin D , and 53 in those given fluoride , estrogen , and calcium with or without vitamin D. It was reduced in all treatment groups ( P less than 0.001 for calcium and P less than 1 x 10(-6 ) for other combinations ) ; fluoride ( one years of treatment ) and estrogen ( but not vitamin D ) independently reduced the rate from that observed with calcium alone ( P less than 0.001 ) . The combination of calcium fluoride , and estrogen was more effective than any other combination ( P less than 0.001 ) . These results provide grounds for optimism about the efficacy of combinations of available agents with sodium fluoride for fracture in postmenopausal osteoporosis", "Summary Daily treatment with 30 mg of sodium fluoride ( NaF ) and 1 g of calcium over a 3-year period increased the bone mineral content ( BMC ) in the spines of women ( n=25 ) with osteoporosis . Determination of the BMC was followed with dual photon absorptiometry ( 137Cs-241Am ) in the third lumbar vertebra . No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium ( n=25 ) , with calcium alone ( n=25 ) , or with placebo ( n=25 ) . No serious side effects were registered . There was , however , minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily", "We report a 4-year r and omized , double-blind , placebo-controlled clinical trial in 236 normal postmenopausal women ( mean age + /- SE , 66.3+/-0.2 years ) who were r and omized to a calcium ( 1600 mg/day as the citrate ) or placebo group . The women were seen every 6 months ; 177 completed the trial . Net percentage changes in each group are given relative to baseline . The differences in net percentage changes ( calcium group minus placebo group ) in medians were : for lumbar spine bone density , 2.0 % ( p proximal femur bone density , 1.3 % ( p = 0.003 ) at year 1 and 1.3 % ( p = 0.015 ) at year 4 ; and for total body bone mineral , 0.4 % ( p = 0.002 ) at year 1 and 0.9 % ( p = 0.017 ) at year 4 . Similar differences at year 4 were : -18.9 % ( p = 0.002 ) for parathyroid hormone ( PTH ) , -11.9 % ( p = 0.026 ) for serum osteocalcin , and -32.2 % ( p = 0.003 ) for urine free pyridinoline . We conclude that long-term administration of calcium supplements to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss . However , the effects on bone loss were weaker than those reported for estrogen , bisphosphonates , or calcitonin therapy , indicating that calcium supplements alone can not substitute for these in treating established osteoporosis . Nonetheless , because of their safety , high tolerance , and low expense , calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age", "The Chinese diet is low in calcium ( less than 500 mg/day on average ) , and previous observational studies have suggested an association between a low calcium intake and risk of hip and vertebral fracture . In this study , we r and omly assigned 200 postmenopausal Chinese women ( age range , 55 - 59 years ) to receive 50 g of milk powder containing 800 mg of calcium per day or to a control group . The following are the mean percentage changes ( and SEs ) in height and bone mineral density ( BMD ) over 24 months : for height , -0.1 + /- 0.2 cm in the milk supplementation group and -0.2 + /- 0.1 cm in the control group ; for BMD at the total hip , -0.06 + /- 0.22 % in the milk supplementation group and -0.88 + /- 0.26 % in the control group ; for BMD at the spine ( L1-L4 ) , -0.56 + /- 0.29 % in the milk supplementation group and -1.5 + /- 0.29 % in the control group ; for total body BMD , -0.32 + /- 0.16 % in the milk supplementation group and -1.2 + /- 0.19 % in the control group ( p loss in terms of both height and BMD than the control group ( p Serum parathyroid hormone ( PTH ) concentration was lower and serum 25-hyroxyvitamin D [ 25(OH)D ] level was higher in the milk supplementation group than the control group at 12 months ( p diet of postmenopausal Chinese women with high calcium milk powder retards bone loss", "A prospect i ve , double-blind , placebo-controlled study of the effect of supplementation with 900 mg/day of calcium , as active absorbable algal calcium ( AAA Ca ) or calcium carbonate ( CaCO3 ) , on lumbar bone mineral density ( BMD ) carried out in elderly in patients with osteoporosis at Katsuragi Hospital was re-evaluated in terms of the effects on vertebral fracture and spondylotic deformity . In addition to the already reported increase in lumbar BMD , AAA Ca was found to inhibit new occurrence of vertebral fracture . Intra-individual variations in L1–L4 BMD ( expressed by the coefficient of variation , indicating the degree of spondylotic deformity , were also inhibited significantly in the group supplemented with AAA Ca ( group A ) , but not in group B ( supplemented with CaCO3 ) , from the level in the placebo-supplement group ( group C ) after 18 months of supple-mentation . According to whole-body dual-energy X-ray absorptiometry ( DXA ) results in the first and second year of the study , whole body mass , lean content , and mineral content , expressed as a percentage of whole body mass , stayed unchanged , while increase of fat content was significantly inhibited in group A , but not in group B , from the level in group C. As to the regional distribution of bone mineral content , the second year/first year value for head bone mineral content was significantly decreased with AAA supplementation compared with placebo , but no significant difference was found between CaCO3 and placebo supplementation . Changes in mineral distribution in the arms , trunk , and legs showed no significant differences among the three groups . In addition to increasing BMD and preventing fracture , AAA Ca , but not CaCO3 , appears to inhibit the occurrence of spondylotic deformity and to decrease body fat content", "UNLABELLED Low BMD and prevalent vertebral fractures are known risk factors for incident vertebral fractures . In 3001 men and women from the Rotterdam Study , prevalent nonvertebral fractures , early menopause , current smoking , and walking aid use were also strong risk factors for incident vertebral fractures . INTRODUCTION Thus far , age , low BMD , and prevalent vertebral fractures are the only well-known risk factors for incident vertebral fractures . Therefore , our aim was to investigate other potential risk factors for incident vertebral fractures in the elderly . MATERIAL S AND METHODS This study was based on the Rotterdam Study , a large prospect i ve population -based cohort study among men and women > or = 55 years of age . For 3001 subjects , spinal radiographs were obtained at baseline and again approximately 6.3 years later . These follow-up radiographs were scored for vertebral fractures using the McCloskey-Kanis method . Whenever a vertebral fracture was detected , the radiograph was compared with the baseline radiograph . If this fracture was not already present at baseline , it was considered incident . At baseline , information on potential risk factors was obtained . RESULTS Low BMD and prevalent vertebral fractures were strong risk factors for incident vertebral fractures in both men and women ( RR 2.3 [ 1.6 - 3.3 ] and 2.2 [ 0.9 - 5.0 ] for men and RR 2.1 [ 1.6 - 2.6 ] and 4.1 [ 2.5 - 6.7 ] for women , respectively ) . For women , age , early menopause ( nonvertebral fractures was a significant independent risk factor ( OR 2.4 [ 1.2 - 4.8 ] ) . CONCLUSION Apart from low BMD and prevalent vertebral fractures , prevalent nonvertebral fractures are associated with an increased incident vertebral fracture risk in men . In women , early menopause , current smoking , and walking aid use are additional independent risk factors for incident vertebral fractures", "This study investigated three aspects of general nutritional status ( dietary intake , biochemical markers , and anthropometric measurements ) in relation to subsequent hip fracture risk by using prospect i ve data from the First National Health and Nutrition Examination Survey ( NHANES I ) epidemiologic follow-up studies . A cohort of 2,513 white women 45 years and over who participated in the NHANES I survey in 1971 - 1975 were subsequently followed in the three follow-up studies in 1982 - 1984 , 1986 , and 1987 , respectively . Multiple nutritional variables were measured at baseline , and 130 incident hip fractures were identified by hospital records or by death certificates during the follow-up period . Cox regression analyses showed that baseline dietary energy intake ; serum albumin ; and weight , body mass index , skinfold , and arm muscle area were significantly and inversely related to subsequent hip fracture risk ( relative risks for a 1-st and ard deviation increment in these variables ranged from 0.68 to 0.83 ) . The authors suggest that poor nutritional status , evident in inadequate dietary intake , reduced serum albumin , and decreased body mass and soft tissues , increases the risk for subsequent hip fracture . The study also showed that age and previous fracture history were significant risk factors ; however , self-reported physical activity , parity , and alcohol use were not significantly related to subsequent hip fracture", "BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year", "Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial", "BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo . Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures", "ABSTRACT Objective : Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis . Supplemental calcium is also generally recommended . This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementation on alendronate treatment . Methods : This 2-year , r and omized , double-blind , multicenter trial enrolled healthy , postmenopausal women with low bone mineral density ( BMD ) . Patients with a dietary calcium intake ≥ 800 mg/day received daily vitamin D 400 IU and alendronate 10 mg/calcium-placebo , alendronate 10 mg/elemental calcium 1000 mg , or alendronate-placebo/calcium 1000 mg ( 2:2:1 ) . Endpoints included BMD , bone turnover markers ( BTMs ) , and adverse events . Results : R and omized patients ( N = 701 ) were an average of 20.4 years postmenopausal . After 24 months , increases in lumbar spine BMD differed significantly between patients receiving calcium alone ( 0.8 % ) and either alendronate alone ( 5.6 % ) or alendronate + calcium ( 6.0 % ) ( p at the trochanter and femoral neck ( p were significantly lower with alendronate-containing treatments than calcium alone ( p Addition of calcium supplementation to alendronate did not significantly increase BMD compared to alendronate alone ( p = 0.29 to 0.97 ) , but did result in a statistically significant , though small , additional reduction in urinary NTx . Adverse events were similar among treatment groups . Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30 % , although discontinuation rates were similar among treatment groups . Conclusions : In postmenopausal women with a daily intake of ≥ 800 mg calcium and 400 IU vitamin D , 24-month treatment with alendronate 10 mg daily with or without calcium 1000 mg result ed in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone . Addition of supplemental calcium to alendronate treatment had no effect on BMD and result ed in a small , though statistically significant , additional reduction in NTx ", "The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain , despite considerable research efforts . With the aim to examine these associations with an improved precision , we used data from a large population -based prospect i ve cohort study in central Sweden . We estimated nutrient intake from a self-administered food-frequency question naire filled in by 60,689 women , aged 40 - 74 years at baseline during 1987 - 1990 . During follow-up , we observed 3986 women with a fracture at any site and 1535 with a hip fracture . Rate ratio of fractures ( RR ) and 95 % CI were estimated using Cox proportional hazards models . We found no dose-response association between dietary calcium intake and fracture risk . The age-adjusted RR of hip fracture was 1.01 ( 95 % CI 0.96 - 1.06 ) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 ( 95 % CI 0.96 - 1.03 ) . Furthermore , women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes : RR 1.07 ( 95 % CI 0.92 - 1.24 ) and RR 1.00 ( 95 % CI 0.79 - 1.27 ) , respectively . Vitamin D intake was not associated with fracture risk . Furthermore , women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures ( 95 % CI 0.88 - 1.17 ) . Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women", "PURPOSE To determine the long-term effects of calcium supplements or placebo on bone density in healthy women at least 3 years postmenopause . PATIENTS AND METHODS Eighty-six women from our previously reported 2-year study agreed to continue on their double-blind treatment allocation ( 1 g elemental calcium or placebo ) for a further 2 years , with 78 women ( 40 on placebo ) reaching the 4-year end point . Median ( interquartile range ) dietary calcium intakes for the whole group were 700 mg ( range 540 to 910 ) per day at baseline , 670 mg ( range 480 to 890 ) per day at 2 years , and 640 mg ( range 460 to 880 ) per day at 4 years . The bone mineral density ( BMD ) of the total body , lumbar spine , and proximal femur was measured every 6 months by dual-energy , x-ray absorptiometry . RESULTS There was a sustained reduction in the rate of loss of total body BMD in the calcium group throughout the 4-year study period ( P = 0.002 ) , and bone loss was significantly less in the calcium-treated subjects in years 2 through 4 also ( difference between groups 0.25 % + /- 0.11 % per year , P = 0.02 ) . In the lumbar spine , bone loss was reduced in the calcium group in year 1 ( P = 0.004 ) , but not subsequently . There was , however , a significant treatment effect at this site over the whole 4-year period ( P = 0.03 ) . In the proximal femur , the benefit from calcium treatment also tended to be greater in the first year and was significant over the 4-year study period in the femoral neck ( P = 0.03 ) and the trochanter ( P = 0.01 ) . Nine symptomatic fractures occurred in 7 subjects in the placebo group and 2 fractures in 2 subjects receiving calcium ( P = 0.037 ) . CONCLUSIONS Calcium supplementation produces a sustained reduction in the rate of loss of total body BMD in healthy postmenopausal women", "PURPOSE Calcium has been shown to have positive effects on bone mineral density in postmenopausal women . However , these effects are small , it is unknown whether they are sustained with long-term use , they have not been shown with intention-to-treat analyses , and the evidence for fracture prevention with calcium monotherapy is inconsistent . METHODS A r and omized controlled trial of calcium ( 1 g/day as the citrate ) in 1471 healthy postmenopausal women ( aged 74+/-4 years ) was performed to assess the effects on bone density and fracture incidence over 5 years . RESULTS Follow-up was complete in 90 % of subjects , and average medication compliance was 55 % to 58 % . Calcium had a significant beneficial effect on bone density ( intention-to-treat analysis ) , with between-groups differences at 5 years of 1.8 % ( spine ) , 1.6 % ( total hip ) , and 1.2 % ( total body ) . Effects were greater in a per- protocol analysis ( 5-year differences of 2.3 % , 2.8 % , and 1.8 % , respectively ) . A total of 425 fractures occurred in 281 women . Hazard ratios , based on time to first fracture , were 0.90 ( 95 % confidence interval [ CI ] , 0.71 - 1.16 ) for any symptomatic fracture , 0.72 ( 95 % CI , 0.44 - 1.18 ) for vertebral , 3.55 ( 95 % CI , 1.31 - 9.63 ) for hip , and 0.65 ( 95 % CI , 0.41 - 1.04 ) for forearm fracture . Per- protocol analysis found respective hazard ratios of 0.86 ( 95 % CI , 0.64 - 1.17 ) , 0.62 ( 95 % CI , 0.33 - 1.16 ) , 3.24 ( 95 % CI , 0.65 - 16.1 ) , and 0.45 ( 95 % CI , 0.24 - 0.87 ) . Height loss was reduced by calcium in the per- protocol population ( P=.03 ) . Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years , but constipation was more common . CONCLUSIONS Calcium results in a sustained reduction in bone loss and turnover , but its effect on fracture remains uncertain . Poor long-term compliance limits its effectiveness", "BACKGROUND There is no consistent evidence , to our knowledge , that calcium supplementation affects bone mineral density ( BMD ) in men , despite male osteoporosis being a common clinical problem . METHODS To determine the effects of calcium supplementation ( 600 mg/d , 1200 mg/d , or placebo ) on BMD in men , we conducted a double-blind , r and omized controlled trial for a 2-year period at an academic clinical research center . A total of 323 healthy men at least 40 years old ( mean age , 57 years ) were recruited by newspaper advertisement . Complete follow-up was achieved in 96 % of subjects . RESULTS The BMD increased at all sites in the group receiving calcium , 1200 mg/d , by 1 % to 1.5 % more than those receiving placebo . The results for the group receiving calcium , 600 mg/d , were not different from the placebo group at any BMD site . There was no interaction between the BMD treatment effect and either age or dietary calcium intake . There were dosage-related , sustained decreases in serum parathyroid hormone ( P total alkaline phosphatase activity ( P = .01 ) , and procollagen type 1 N-terminal propeptide ( P Tooth loss , constipation , and cramps were unaffected by calcium supplementation , falls tended to be less frequent in the group receiving calcium , 1200 mg/d , but vascular events tended to be more common in the groups receiving calcium vs the group receiving placebo . CONCLUSION Calcium , 1200 mg/d , has effects on BMD in men comparable with those found in postmenopausal women but a dosage of 600 mg/d is ineffective for treating BMD . TRIAL REGISTRATION actr.org.au Identifier : 012605000274673" ]

[ "BACKGROUND AND OBJECTIVE : Relative deficiency of dietary omega 3 polyunsaturated fatty acids ( n-3 PUFA ) has been implicated in the rising allergy prevalence in Westernized countries . Fish oil supplementation may provide an intervention strategy for primary allergy prevention . The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease . METHODS : In a double-blind r and omized controlled trial , 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control ( olive oil ) , from birth to age 6 months . PUFA levels were measured in 6-month-old infants ’ erythrocytes and plasma and their mothers ’ breast milk . Eczema , food allergy , asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age . RESULTS : At 6 months of age , infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher ( both P erythrocyte arachidonic acid levels were lower ( P = .003 ) in the fish oil group . Although n-3 PUFA levels at 6 months were associated with lower risk of eczema ( P = .033 ) and recurrent wheeze ( P = .027 ) , the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes . Specifically , between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization , eczema , asthma , or food allergy . CONCLUSIONS : Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease", "Background Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing . We examined the effect of prenatal vitamin D on childhood wheezing in an interventional study . Methods We r and omised 180 pregnant women at 27 weeks gestation to either no vitamin D , 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol , in an ethnically stratified , r and omised controlled trial . Supplementation improved but did not optimise vitamin D status . Research ers blind to allocation assessed offspring at 3 years . Primary outcome was any history of wheeze assessed by vali date d question naire . Secondary outcomes included atopy , respiratory infection , impulse oscillometry and exhaled nitric oxide . Primary analyses used logistic and linear regression . Results We evaluated 158 of 180 ( 88 % ) offspring at age 3 years for the primary outcome . Atopy was assessed by skin test for 95 children ( 53 % ) , serum IgE for 86 ( 48 % ) , exhaled nitric oxide for 62 ( 34 % ) and impulse oscillometry of acceptable quality for 51 ( 28 % ) . We found no difference between supplemented and control groups in risk of wheeze [ no vitamin D : 14/50 ( 28 % ) ; any vitamin D : 26/108 ( 24 % ) ( risk ratio 0.86 ; 95 % confidence interval 0.49 , 1.50 ; P = 0.69 ) ] . There was no significant difference in atopy , eczema risk , lung function or exhaled nitric oxide between supplemented groups and controls . Conclusion Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level , was not associated with decreased wheezing in offspring at age three years . Trial Registration Controlled-Trials.com IS RCT", "BACKGROUND Some breastfed infants with atopic eczema benefit from elimination of cow milk , egg , or other antigens from their mother 's diet . Maternal dietary antigens are also known to cross the placenta . OBJECTIVES To assess the effects of prescribing an antigen avoidance diet during pregnancy or lactation , or both , on maternal and infant nutrition and on the prevention or treatment of atopic disease in the child . SEARCH METHODS We search ed the Cochrane Pregnancy and Childbirth Group 's Trials Register ( 6 July 2012 ) . SELECTION CRITERIA All r and omized or quasi-r and omized comparisons of maternal dietary antigen avoidance prescribed to pregnant or lactating women . We excluded trials of multimodal interventions that included manipulation of the infant 's diet other than breast milk or of non-dietary aspects of the infant 's environment . DATA COLLECTION AND ANALYSIS We extracted data from published reports , supplemented by additional information received from the trialists we contacted . MAIN RESULTS The evidence from five trials , involving 952 participants , does not suggest a protective effect of maternal dietary antigen avoidance during pregnancy on the incidence of atopic eczema during the first 18 months of life . Data on allergic rhinitis or conjunctivitis , or both , and urticaria are limited to a single trial each and are insufficient to draw meaningful inferences . Longer-term atopic outcomes have not been reported . The restricted diet during pregnancy was associated with a slightly but statistically significantly lower mean gestational weight gain , a non-significantly higher risk of preterm birth , and a non-significant reduction in mean birthweight . The evidence from two trials , involving 523 participants , did not observe a significant protective effect of maternal antigen avoidance during lactation on the incidence of atopic eczema during the first 18 months or on positive skin-prick tests to cow milk , egg , or peanut antigen at one , two , or seven years . One crossover trial involving 17 lactating mothers of infants with established atopic eczema found that maternal dietary antigen avoidance was associated with a non-significant reduction in eczema severity . AUTHORS ' CONCLUSIONS Prescription of an antigen avoidance diet to a high-risk woman during pregnancy is unlikely to reduce substantially her child 's risk of atopic diseases , and such a diet may adversely affect maternal or fetal nutrition , or both . Prescription of an antigen avoidance diet to a high-risk woman during lactation may reduce her child 's risk of developing atopic eczema , but better trials are needed . Dietary antigen avoidance by lactating mothers of infants with atopic eczema may reduce the severity of the eczema , but larger trials are needed", "Antioxidant intakes in pregnancy may influence fetal immune programming and the risk of allergic disease . We investigated associations between maternal intakes of β-carotene , vitamin C , vitamin E , copper and zinc , and infant allergic outcomes . Antioxidant intakes of pregnant women ( n = 420 ) assessed prospect ively by a food frequency question naire , were examined in relation to allergic outcomes at 1 year of age ( n = 300 ) . The main relationships with allergic outcomes were seen with dietary vitamin C and copper . Specifically , higher maternal dietary vitamin C intake was associated with a reduced risk of any diagnosed infant allergic disease and wheeze . After adjustment for potential confounders the relationship with wheeze remained statistically significant . There was also an inverse linear relationship between vitamin C and food allergy . Higher dietary copper intake was associated with reduced risk of eczema , wheeze and any allergic disease . The relationship with wheeze and any allergic disease remained statistically significant in multivariate analysis , and there was also an inverse linear relationship between copper and food allergy . However , these relationships were only seen for nutrients present in food . There were no relationships between β-carotene , vitamin E or zinc and any allergic outcomes . In summary , this study suggests that maternal diet of fresh foods rich in vitamin C is associated with reduced risk of infant wheeze , and that copper intake is associated with reduced risk of several allergic outcomes", "Objective To evaluate a multistrain , high-dose probiotic in the prevention of eczema . Design A r and omised , double-blind , placebo-controlled , parallel group trial . Setting s Antenatal clinics , research clinic , children at home . Patients Pregnant women and their infants . Interventions Women from 36 weeks gestation and their infants to age 6 months received daily either the probiotic ( Lactobacillus salivarius CUL61 , Lactobacillus paracasei CUL08 , Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20 ; total of 1010 organisms/day ) or matching placebo . Main outcome measure Diagnosed eczema at age 2 years . Infants were followed up by question naire . Clinical examination and skin prick tests to common allergens were done at 6 months and 2 years . Results The cumulative frequency of diagnosed eczema at 2 years was similar in the probiotic ( 73/214 , 34.1 % ) and placebo arms ( 72/222 , 32.4 % ; OR 1.07 , 95 % CI 0.72 to 1.6 ) . Among the secondary outcomes , the cumulative frequency of skin prick sensitivity at 2 years was reduced in the probiotic ( 18/171 ; 10.5 % ) compared with the placebo arm ( 32/173 ; 18.5 % ; OR 0.52 , 95 % CI 0.28 to 0.98 ) . The statistically significant differences between the arms were mainly in sensitisation to cow 's milk and hen 's egg proteins at 6 months . Atopic eczema occurred in 9/171 ( 5.3 % ) children in the probiotic arm and 21/173 ( 12.1 % ) in the placebo arm ( OR 0.40 , 95 % CI 0.18 to 0.91 ) . Conclusions The study did not provide evidence that the probiotic either prevented eczema during the study or reduced its severity . However , the probiotic seemed to prevent atopic sensitisation to common food allergens and so reduce the incidence of atopic eczema in early childhood . Trial registration Number IS RCT N26287422", "BACKGROUND The impact of breast milk feeding on susceptibility to asthma in childhood is highly controversial , due in part to failure of the majority of studies in the area to adequately account for key confounders exemplified by respiratory infection history , plus the effects of recall bias . METHODS As part of a prospect i ve cohort study on the role of respiratory infections in asthma development in high-risk children , we measured the concentration of a panel of anti-infective proteins in maternal milk sample s and analyzed associations between these and subsequent atopy- , infection- , and asthma-related outcomes prospect ively to age 10 years . RESULTS We observed significant but transient inverse associations between the concentration of milk proteins and susceptibility to upper respiratory infections in year 1 only , and parallel but positive transient associations with early lower respiratory infections and atopy . No associations were seen with asthma-related outcomes . CONCLUSIONS Breast milk feeding may influence the expression of inflammatory symptoms associated with respiratory infections and atopy in early life , but these effects appear to be inconsistent and transient . The heterogeneous nature of breast-feeding effects suggests it may influence systemic immunoinflammatory function at several different levels", "BACKGROUND Extended breast-feeding is recommended for newborn children at risk of allergy-associated diseases , but the evidence of a protective effect on sensitization and these diseases remains elusive . OBJECTIVE The aim of this study was to investigate the effects of the duration of exclusive breast-feeding on the development of sensitization in preschool children . METHODS Information on breast-feeding was gathered by interviews involving 335 children aged 1 , 6 , and 12 months from the Copenhagen Prospect i ve Study on Asthma in Childhood2000 birth cohort born to mothers with a history of asthma . Skin prick test responses and specific IgE levels against 12 common inhalant and 10 food allergens were assessed longitudinally at ages ½ year , 1½ years , 4 years , and 6 years . Eczema , wheeze/asthma , and allergic rhinitis were diagnosed at the Copenhagen Prospect i ve Studies on Asthma in Childhood clinic at 7 years of age , strictly adhering to predefined algorithms . Associations between duration of exclusive breast-feeding and outcomes were analyzed by logistic regression . RESULTS We found no significant association between duration of exclusive breast-feeding and development of sensitization in the first 6 years of life ( odds ratio [ OR ] : ½ year , 1.10 [ 95 % CI , 0.90 - 1.36 ] ; 1½ years , 1.15 [ 95 % CI , 0.97 - 1.36 ] ; 4 years , 1.08 [ 95 % CI , 0.93 - 1.25 ] ; and 6 years , 0.96 [ 95 % CI , 0.84 - 1.10 ] ) or with current eczema , wheeze/asthma , and allergic rhinitis at age 7 years ( OR , 1.07 [ 95 % CI , 0.92 - 1.24 ] ; OR , 0.97 [ 95 % CI , 0.82 - 1.14 ] ; and OR , 1.02 [ 95 % CI , 0.84 - 1.23 ] , respectively ) . Adjusting for reverse causation by excluding children with eczema , wheeze , or a positive skin prick test response before ending exclusive breast-feeding did not alter the results . CONCLUSION Exclusive breast-feeding does not affect sensitization in early childhood or associated diseases at 7 years of age in at-risk children", "Early exposure to solid foods in infancy has been associated with the development of allergic diseases . However , scientific evidence for this is conflicting . The aim of this study was to examine the association between early exposure to solid foods in the infant 's diet and the development of eczema up to 4 years of age . We conducted an etiologic case-control study nested in the PIPO cohort ( Prospect i ve Cohort on the Influence of Perinatal Factors on the Occurrence of Asthma and Allergies ) . In this cohort data on nutrition , environmental exposures and parent-reported eczema were collected prospect ively starting from 5 months pregnancy by means of question naires administered during two home visits and semi-annual postal question naires . In addition , detailed information on the timing of introduction of solid foods at individual food item level was collected at 1 year of age . Adjusted odds ratios and 95 % confidence intervals were computed using logistic regression analysis as a measure of association between eczema and the timing of exposure to solid foods . Early introduction ( within the first 4 months ) of solid foods was inversely associated with eczema up to 4 years of age ( adj OR : 0.49 ; 95 % CI : 0.32 - 0.74 ) . Moreover , we found that early exposure to solid foods was associated with a reduced risk for eczema only among children with allergic parents ( adj OR : 0.35 ; 95 % CI : 0.20 - 0.63 ) , whereas no significant effect was found among children with non-allergic parents ( adj OR : 0.69 ; 95 % CI : 0.37 - 1.29 ) . The results of this study show that early exposure to solid foods is associated with less parent-reported eczema in children , particularly among children with allergic parents . Therefore , the current study does not support a delayed introduction of solid foods for the prevention of eczema in childhood" ]

[ "PURPOSE The primary goal of pulmonary rehabilitation ( PR ) is for patients to achieve and maintain their maximum level of independence and functioning in the community . Traditional PR uses a predominantly aerobic/endurance approach to rehabilitation with little or no inclusion of exercises to increase strength . Few studies have investigated the impact of resistance training on PR despite growing evidence supporting its efficacy to improve physical function ( functional fitness ) in both healthy individuals and those with chronic disease . The purpose of this study was to investigate the effect of single-set resistance training on strength and functional fitness outcomes in PR patients . METHODS Twenty PR patients , 60 to 81 years old , were r and omly assigned to an 8-week endurance-based PR program ( ET ) or an ET plus resistance training program ( RT ) . RESULTS Strength increased in RT ( P decreased in ET for both upper and lower body . Functional fitness improved ( P RT compared with 2 tests for ET . CONCLUSIONS Single set RT can elicit significant improvements in both strength and functional fitness , which is not obtained by traditional PR alone . Our results are comparable to other studies with similar outcomes using multiple-set RT protocol s. These findings may have important implication s for program design , application , and adherence in PR", "& NA ; The purpose of this study was to compare the effects of a strength training‐enhanced program and a traditional pulmonary rehabilitation ( PR ) program on functional fitness ( FF ) in older patients with chronic obstructive pulmonary disease ( COPD ) , using the Senior Fitness Test . Twenty patients were recruited from an outpatient PR program . After completing baseline measures , including muscular strength and the Senior Fitness Test , patients were r and omly assigned to the strength training program ( TR+ST , n = 10 ) or traditional PR program ( TR , n = 10 ) . Patients completed 16 exercise sessions that were conducted twice a week for 8–10 weeks , after which patients repeated outcome measurements . Independent t tests were conducted to determine whether groups differed between measures . Both the TR+ST and TR groups improved on all FF measures . Moderate effect sizes were found for two of the FF measures when the groups were compared . The addition of strength training to PR may have a favorable impact on FF in older patients with COPD", "Disability and exertional dyspnea associated with chronic obstructive pulmonary disease has led to the development of rehabilitation programmes that aim to increase exercise tolerance and relief of dyspnea . To evaluate whether aerobic training ( training groups P1 and P4 ) , strength training ( P2 and P5 ) or a combination of both ( P4 and P6 ) is useful , 69 patients ( 44 m/25 f ) with moderate to severe COPD were r and omised to a three week inpatient training program . The training consisted of three weekly twenty minute exercise sessions without ( P1 - P3 ) or with supplemental oxygen ( P4 - P6 ) on a calibrated ergocycle ( 70 % W(max ) ) or three weekly sessions of 20 - 25 repetitions of 2 - 4 training series ( 40 % W(max ) ) or a combination of both . In general , the programme failed to demonstrate significant changes in lung function and arterial blood gases . Evaluation of exercise capacity via the six-minute-walking test ( 6MT ) yielded a significant increase of the walking distance in all groups except P2 ( 60 - 83 m ) , The time to finish a test-set of daily activities ( TAF ) was reduced in all groups ( 5 - 58 sec ) and reached significance in P1 , P3 , P5 and P6 . After the 6MT , exertional dyspnea improved in all groups except P4 and was significant in P1 and P3 ; after the TAF , dyspnea again was reduced in all groups with a significant change in P2 and P5 . These data support the hypotheses that a short term inpatient training programme is suitable to improve exercise-capacity and dyspnea . Patients with advanced disease ( P4 - P6 ) show greater benefits with strength training ( alone or in combination with aerobic training ) while for patients with moderate disease ( P1 - P3 ) aerobic training is favourable . These changes may translate into improved performance of daily activities and general well-being", "The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Forty-five patients with moderate to severe COPD were r and omized to 12 wk of aerobic training alone ( AERO ) or combined with strength training ( AERO + ST ) . The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle , and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises . Measurements of peripheral muscle strength , thigh muscle cross-sectional area ( MCSA ) by computed tomographic scanning , maximal exercise capacity , 6-min walking distance ( 6MWD ) , and quality of life with the chronic respiratory question naire were obtained at baseline and after training . Thirty-six patients completed the program and constituted the study group . The strength of the quadriceps femoris increased significantly in both groups ( p thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 + /- 13 % and 15 + /- 9 % , respectively ( p 0.05 ) . These changes were significantly different in the two study groups ( p increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups . The changes in peak exercise work rate , 6MWD , and quality of life were comparable in the two groups . In conclusion , the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass , but does not provide additional improvement in exercise capacity or quality of life", "Aerobic exercise training is used for rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) , although it has little effect on muscle weakness and atrophy . Resistance training may be a useful addition to aerobic programs for these patients . The purpose of the present study was to investigate the effects of resistance training in addition to aerobic training on functional outcomes in patients with COPD . Seventeen COPD patients enrolled in an aerobic-based program that met twice a week were assigned to a 12-week control/aerobic [ CON : n=8 ; 63 ( 8) years ; mean ( SD ) ] or a resistance/aerobic group [ RES : n=9 ; 61 ( 7 ) years ] . RES trained an additional twice a week on 12 resistance machines , performing three sets of 8–12 repetitions at 32–64 % of their one-repetition maximum ( 1-RM ) lifts . RES ( P increased upper ( 36 % ) and lower ( 36 % ) body strength , as well as lean body mass ( 5 % ) , while CON showed little to no change . The 12-min walk distance increased ( P Measurements of three of the eight tasks of activities of daily living improved in RES ( P improved functional outcomes in COPD patients that were currently involved in an aerobic training program", "Many patients with chronic obstructive pulmonary disease ( COPD ) report greater limitation for activities involving the upper extremities than the lower extremities . Exercise training has generally emphasized lower-extremity exercise . We design ed and evaluated two simple , practical , and widely applicable upper-extremity training programs in 45 patients with COPD participating concurrently in a comprehensive , multidisciplinary pulmonary rehabilitation program . Patients were r and omly assigned to one of the following three groups : ( 1 ) gravity-resistance ( GR ) upper-extremity training ; ( 2 ) modified proprioceptive neuromuscular facilitation ( PNF ) upper-extremity training ; or ( 3 ) no upper-extremity training ( control ) . Patients were evaluated before and after at least six weeks of uninterrupted training . Twenty-eight patients completed the study . Compared to controls , both GR and PNF patients demonstrated improved performance on tests specific to the training performed ( upper-extremity performance test , maximal level and endurance on isokinetic arm cycle ) . There were no significant changes on isotonic arm cycle , ventilatory muscle endurance , or simulated activities of daily-living tests . Ratings of perceived breathlessness and fatigue decreased significantly in all groups for several tests . We conclude that specific upper-extremity training may be beneficial in the rehabilitation of patients with COPD and warrants further investigation", "BACKGROUND AND OBJECTIVE Skeletal muscle dysfunction contributes to exercise limitation in patients with chronic obstructive pulmonary disease ( COPD ) . Strength training increases muscle strength and muscle mass , but there is an ongoing debate on the additional effect concerning the exercise capacity . The purpose of this study was to compare the effects of three different exercise modalities in patients with COPD including endurance training ( ET ) , progressive strength training ( ST ) and the combination of strength training and endurance training ( CT ) . DESIGN A prospect i ve r and omized trial . METHODS Thirty-six patients with COPD were r and omly allocated either to ET , ST , or CT . Muscle strength , cardiopulmonary exercise testing , lung function testing and quality of life were assessed before and after a 12-week training period . RESULTS Exercise capacity ( Wmax ) increased significantly in all three training groups with increase of peak oxygen uptake ( VO2peak ) in all three groups , reaching statistical significance in the ET group and the CT group . Muscle strength ( leg press , bench press , bench pull ) improved in all three training groups , with a higher improvement in the ST ( + 39.3 % , + 20.9 % , + 20.3 % ) and the CT group ( + 43.3 % , + 18.1 % , + 21.6 % ) compared to the ET group ( + 20.4 % , + 6.4 % , + 12.1 % ) . CONCLUSIONS Progressive strength training alone increases not only muscle strength and quality of life , but also exercise capacity in patients with COPD , which may have implication s in prescription of training modality . CLINICAL TRIALS.GOV IDENTIFIER : NCT01091623", "BACKGROUND Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease . We undertook a r and omised controlled trial to assess the effect of outpatient pulmonary rehabilitation on use of health care and patients ' wellbeing over 1 year . METHODS 200 patients with disabling chronic lung disease ( the majority with chronic obstructive pulmonary disease ) were r and omly assigned a 6-week multidisciplinary rehabilitation programme ( 18 visits ) or st and ard medical management . Use of health services was assessed from hospital and general- practice records . Analysis was by intention to treat . FINDINGS There was no difference between the rehabilitation ( n=99 ) and control ( n=101 ) groups in the number of patients admitted to hospital ( 40 vs 41 ) but the number of days these patients spent in hospital differed significantly ( mean 10.4 [ SD 9.7 ] vs 21.0 [ 20.7 ] , p=0.022 ) . The rehabilitation group had more primary -care consultations at the general-practitioner 's premises than did the control group ( 8.6 [ 6.8 ] vs 7.3 [ 8.3 ] , p=0.033 ) but fewer primary -care home visits ( 1.5 [ 2.8 ] vs 2.8 [ 4.6 ] , p=0.037 ) . Compared with control , the rehabilitation group also showed greater improvements in walking ability and in general and disease-specific health status . INTERPRETATION For patients chronically disabled by obstructive pulmonary disease , an intensive , multidisciplinary , outpatient programme of rehabilitation is an effective intervention , in the short term and the long term , that decreases use of health services", "The purpose of this study was to evaluate whether strength or recreational activities are a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Thirty-three patients with moderate to severe COPD were r and omly assigned to 12 weeks of aerobic combined with strength training ( AERO+ST ) or combined with recreational activities ( AERO+RA ) . The AERO regimen consisted of three weekly 20-min walking exercise sessions ; the ST regimen included three series of 10 repetitions of four exercises ; and the RA regimen consisted of training using exercise balls to perform smoothly for instrumental activity of daily living . Baseline and after-training measurements of peripheral muscular strength and endurance , cardio respiratory fitness , and 6-min walking distance were obtained , whereas quality of life was assessed with the Short Form 36 question naire . Change in grip strength showed a significant difference between the AERO+ST group ( 8.3±6.7 % ) and the control group ( −1.3±10.5 % ) , and AERO+RA group ( −4.7±5.6 % ) ( P in percentage change in peak & OV0312;o2 between the AERO+ST group ( 5.1±11.8 % ) and the control group ( −9.2±8.6 % ) ( P In the health-related quality of life scores , there was a significant difference in mean percentage change in physical functioning between the AERO+ST group ( 7.9±24.4 % ) and the control group ( −14.8±19.1 % ) ( P in mean percentage change in social functioning between the AERO+RA group ( 9.4±20.0 % ) and the control group ( −14.9±23.2 % ) ( P in mean percentage change in mental health was also found between the AERO+RA group ( 12.2±12.4 % ) and the control group ( −5.0±7.8 % ) ( P of exercise that use different muscles involving the whole body , such as recreational activities , as they are an appropriate approach to stimulating physical activity and to improving functional fitness gradually while improving health-related quality of life , though it is necessary to practice exercises for maintenance and improvement in patients with COPD . Die vorliegende Studie soll ermitteln , ob Krafttraining oder Freizeitaktivitäten das Aerobictraining von Patienten mit chronisch-obstruktiver Lungenerkrankung ( COPD ) sinnvoll ergänzen . Insgesamt wurden 33 Patienten mit moderater bis schlimmer COPD einem 12-wöchigen Aerobictraining mit Krafttraining ( AERO+ST ) oder einem 12-wöchigen Aerobictraining mit Freizeitaktivitäten ( AERO+RA ) r and omisiert zugeordnet . Das AERO-Programm umfasste drei 20-minütige Gehübungen pro Woche , das ST-Programm dreimal je 10 Wiederholungen mit vier Übungen und das RA-Programm ein Training mit Gymnastikbällen , die wichtige Aktivitäten i m Alltagsleben erleichtern sollten . Messungen wie periphere Muskelkraft und Ausdauer , kardiorespiratorische Fitness und 6-minütiges Gehen gegenüber Baseline und nach dem Training wurden erhalten , und die Lebensqualität wurde mittels Fragebogen SF-36 beurteilt . Veränderungen bei der Griffstärke wiesen einen signifikanten Unterschied zwischen der AERO+ST Gruppe ( 8,3±6,7 % ) und der Kontrollgruppe ( −1,3±10,5 % ) und der AERO+RA Gruppe ( −4,7±5,6 % ) auf ( P wurde ein signifikanter Anstieg bei der prozentualen Veränderung von & OV0312;o2 maximal zwischen der AERO+ST Gruppe ( 5,1±11,8 % ) und der Kontrollgruppe ( −9,2±8,6 % ) ( P den gesundheitsbezogenen Lebensqualitäts-Scores best and ein signifikanter Unterschied in der durchschnittlichen prozentualen Veränderung bei der körperlichen Funktion zwischen der AERO+ST Gruppe ( 7,9±24,4 % ) und der Kontrollgruppe ( −14,8±19,1 % ) ( P Ein signifikanter Unterschied wurde bei der durchschnittlichen prozentualen Veränderung bei der gesellschaftlichen Funktionsfähigkeit zwischen der AERO+RA Gruppe ( 9,4±20,0 % ) und der Kontrollgruppe ( −14,9±23,2 % ) beobachtet ( P signifikanter Unterschied in der durchschnittlichen prozentualen Veränderung in der seelischen Gesundheit zwischen der AERO+RA Gruppe ( 12,2±12,4 % ) und der Kontrollgruppe ( −5,0±7,8 % ) ( P pacientes afectos de enfermedad pulmonar obstructiva crónica ( EPOC ) . Se distribuyeron de manera aleatoria a 33 pacientes afectos de EPOC de moderada a grave para participar en un programa de 12 semanas de ejercicios aeróbicos combinados ya fuese con ejercicios de desarrollo de fuerza ( AERO+EF ) o con actividades recreativas ( AERO+AR ) . El régimen de ejercicios aeróbicos ( AERO ) consistió en 3 sesiones semanales de caminatas de 20 minutos de duración cada una ; el régimen EF consistió en 3 series de 10 repeticiones de 4 tipos de ejercicios ; y el régimen AR consistió en un programa con pelotas para ejercicios , para realizar actividades instrumentales de la vida cotidiana . Al inicio del estudio y una vez terminado el régimen de ejercicios se obtuvieron datos sobre la fuerza muscular periférica , la resistencia , la aptitud cardiorrespiratoria , y tras una caminata de 6 minutos . Para evaluar la calidad de vida se utilizó el cuestionario reducido de 36 preguntas ( Short Form 36 ) . Los cambios en la fuerza de agarre mostraron una diferencia significativa entre el grupo que recibió AERO+EF ( 8,3±6,7 % ) y el grupo de referencia ( −1,3±10,5 % ) , y el grupo que recibió AERO+AR ( −4,7±5,6 % ) ( P los cambios en los valores porcentuales máximos del & OV0312;o2 entre el grupo que realizó AERO+EF ( 5,1±11,8 % ) y el grupo de referencia ( −9,2±8,6 % ) ( P cambios de los porcentajes del funcionamiento social entre el grupo que realizó AERO+AR ( 9,4±20,0 % ) y el grupo de referencia ( −14,9±23,2 % ) ( P significativa en la media de los cambios de los porcentajes relacionados con la salud mental entre el grupo que realizó AERO+AR ( 12,2±12,4 % ) y el grupo de referencia ( −5,0±7,8 % ) ( P exercices aérobic chez les patients souffrant de maladie pulmonaire obstructive chronique ( MPCO ) . Trente-trois patients souffrant de MPCO modérée à sévère ont été affectées de manière aléatoire à un programme de 12 semaines d'exercices d'aérobic combinés avec des activités fortifiantes ( AERO+ST ) ou des activités de loisirs ( AERO+RA ) . Le programme AERO comportait trois séances hebdomadaires de 20 minutes d'exercices de marche , le programme ST consistait en trois séries de 10 répétitions de quatre exercices , et le programme RA se composait d'exercice de formation utilisant des ballons , destinés à faciliter les activités d'utilisation d'instruments au quotidien . Des mesures de référence et après exercice de la force musculaire périphérique et de l'endurance et des capacités cardio-respiratoires après un exercice de marche de 6 minutes ont été effectuées , t and is que la qualité de vie a été évaluée grâce à un rapide question naire en 36 points . L'évolution de la force de préhension témoigne d'une différence significative entre le groupe AERO+ST ( 8,3±6,7 % ) et le groupe de contrôle ( −1,3±10,5 % ) , et le groupe AERO+RA ( −4,7±5,6 % ) ( P changement du pourcentage de pic de & OV0312;o2 entre le groupe AERO+ST ( 5,1±11,8 % ) et le groupe de contrôle ( −9,2±8,6 % ) ( P scores de qualité de vie associés à la santé , une différence significative a été constatée dans l'évolution du pourcentage moyen de fonctionnalité physique entre le groupe AERO+ST ( 7,9±24,4 % ) et le groupe de contrôle ( −14,8±19,1 % ) ( P du pourcentage moyen de fonctionnalité sociale entre le groupe AERO+RA ( 9,4±20,0 % ) et le groupe de contrôle ( −14,9±23,2 % ) ( P du pourcentage moyen de santé mentale entre le groupe AERO+RA ( 12,2±12,4 % ) et le groupe de contrôle ( −5,0±7,8 % ) ( P qualité de vie associée à la santé , bien qu'il soit également nécessaire de pratiquer des exercices d'entretien et d'amélioration chez les patients souffrant de MPCO" ]

[ "Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder ( ADHD ) in several , mostly uncontrolled studies . This pilot study is design ed to test the feasibility and safety of using a double-blind placebo feedback-controlled design and to explore the initial efficacy of individualized EEG-neurofeedback training in children with ADHD . Fourteen children ( 8–15 years ) with ADHD defined according to the DSM-IV-TR criteria were r and omly allocated to 30 sessions of EEG-neurofeedback ( n = 8) or placebo feedback ( n = 6 ) . Safety measures ( adverse events and sleep problems ) , ADHD symptoms and global improvement were monitored . With respect to feasibility , all children completed the study and attended all study visits and training sessions . No significant adverse effects or sleep problems were reported . Regarding the expectancy , 75 % of children and their parent(s ) in the active neurofeedback group and 50 % of children and their parent(s ) in the placebo feedback group thought they received placebo feedback training . Analyses revealed significant improvements of ADHD symptoms over time , but changes were similar for both groups . This pilot study shows that it is feasible to conduct a rigorous placebo-controlled trial to investigate the efficacy of neurofeedback training in children with ADHD . However , a double-blind design may not be feasible since using automatic adjusted reward thresholds may not work as effective as manually adjusted reward thresholds . Additionally , implementation of active learning strategies may be an important factor for the efficacy of EEG-neurofeedback training . Based on the results of this pilot study , changes are made in the design of the ongoing study", "Neurofeedback treatment has been demonstrated to reduce inattention , impulsivity and hyperactivity in children with attention deficit/hyperactivity disorder ( ADHD ) . However , previous studies did not adequately control confounding variables or did not employ a r and omized reinforcer-controlled design . This study addresses those method ological shortcomings by comparing the effects of the following two matched biofeedback training variants on the primary symptoms of ADHD : EEG neurofeedback ( NF ) aim ing at theta/beta ratio reduction and EMG biofeedback ( BF ) aim ing at forehead muscle relaxation . Thirty-five children with ADHD ( 26 boys , 9 girls ; 6–14 years old ) were r and omly assigned to either the therapy group ( NF ; n = 18 ) or the control group ( BF ; n = 17 ) . Treatment for both groups consisted of 30 sessions . Pre- and post-treatment assessment consisted of psychophysiological measures , behavioural rating scales completed by parents and teachers , as well as psychometric measures . Training effectively reduced theta/beta ratios and EMG levels in the NF and BF groups , respectively . Parents reported significant reductions in primary ADHD symptoms , and inattention improvements in the NF group were higher compared to the control intervention ( BF , dcorr = −.94 ) . NF training also improved attention and reaction times on the psychometric measures . The results indicate that NF effectively reduced inattention symptoms on parent rating scales and reaction time in neuropsychological tests . However , regarding hyperactivity and impulsivity symptoms , the results imply that non-specific factors , such as behavioural contingencies , self-efficacy , structured learning environment and feed-forward processes , may also contribute to the positive behavioural effects induced by neurofeedback training", "Objective : Preparing for a definitive r and omized clinical trial ( RCT ) of neurofeedback ( NF ) for ADHD , this pilot trial explored feasibility of a double-blind , sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week . Method : Unmedicated 6- to 12-year-olds with Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; DSM-IV ) ADHD were r and omized to active NF versus sham-NF and to 2X versus 3X/week treatment frequency . Frequency switch was allowed after Treatment 24 . Results : In two school years , 39 participants were recruited and 34 ( 87 % ) completed all 40 treatments . Child/parent guesses about assigned treatment were no better than chance . At Treatment 24 , 38 % chose 2X/week and 62 % chose 3X/week . Both active NF and sham yielded large pre – post improvement on parent ratings but NF no more than sham . Conclusion : Blinding appears to work , and sham does not prevent recruitment/retention . Treatment frequency of 3X/week seems preferred over 2X/week and was as effective . A large double-blind RCT is feasible and necessary to test specific NF effectiveness", "OBJECTIVE : To evaluate sustained improvements 6 months after a 40-session , in-school computer attention training intervention using neurofeedback or cognitive training ( CT ) administered to 7- to 11-year-olds with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS : One hundred four children were r and omly assigned to receive neurofeedback , CT , or a control condition and were evaluated 6 months postintervention . A 3-point growth model assessed change over time across the conditions on the Conners 3–Parent Assessment Report ( Conners 3-P ) , the Behavior Rating Inventory of Executive Function Parent Form ( BRIEF ) , and a systematic double-blinded classroom observation ( Behavioral Observation of Students in Schools ) . Analysis of variance assessed community-initiated changes in stimulant medication . RESULTS : Parent response rates were 90 % at the 6-month follow-up . Six months postintervention , neurofeedback participants maintained significant gains on Conners 3-P ( Inattention effect size [ ES ] = 0.34 , Executive Functioning ES = 0.25 , Hyperactivity/Impulsivity ES = 0.23 ) and BRIEF subscales including the Global Executive Composite ( ES = 0.31 ) , which remained significantly greater than gains found among children in CT and control conditions . Children in the CT condition showed delayed improvement over immediate postintervention ratings only on Conners 3-P Executive Functioning ( ES = 0.18 ) and 2 BRIEF subscales . At the 6-month follow-up , neurofeedback participants maintained the same stimulant medication dosage , whereas participants in both CT and control conditions showed statistically and clinical ly significant increases ( 9 mg [ P = .002 ] and 13 mg [ P Neurofeedback participants made more prompt and greater improvements in ADHD symptoms , which were sustained at the 6-month follow-up , than did CT participants or those in the control group . This finding suggests that neurofeedback is a promising attention training treatment for children with ADHD", "Objective : Additional treatments with persisting benefit are needed for ADHD . Because ADHD often shows excessive theta electroencephalogram ( EEG ) power , low beta , and excessive theta-beta ratio ( TBR ) , a promising treatment is neurofeedback ( NF ) downtraining TBR . Although several nonblind r and omized clinical trials ( RCTs ) show a medium-large benefit for NF , a well-blinded , sham-controlled RCT is needed to differentiate specific from nonspecific effects . Method : Experts in NF , ADHD , clinical trials , and statistics collaborated to design a double-blind multisite RCT . Results / Conclusion : At four sites , 180 children aged 7 to 10 years with rigorously diagnosed ADHD and TBR ≥ 5 will be r and omized to active TBR-NF versus sham NF of equal duration , intensity , and appearance . Sham , utilizing prerecorded EEGs with participant artifacts superimposed , will keep participants and staff blind . Treatment fidelity will be trained/monitored by acknowledged NF leaders . Multidomain assessment s before , during , and after treatment ( follow-up to 2 years ) will also include tests of blinding and sham inertness", "Objective : To evaluate the efficacy of 2 computer attention training systems administered in school for children with attention-deficit hyperactivity disorder ( ADHD ) . Method : Children in second and fourth grade with a diagnosis of ADHD ( n = 104 ) were r and omly assigned to neurofeedback ( NF ) ( n = 34 ) , cognitive training ( CT ) ( n = 34 ) , or control ( n = 36 ) conditions . A 2-point growth model assessed change from pre-post intervention on parent reports ( Conners 3-Parent [ Conners 3-P ] ; Behavior Rating Inventory of Executive Function [ BRIEF ] rating scale ) , teacher reports ( Swanson , Kotkin , Agler , M-Flynn and Pelham scale [ SKAMP ] ; Conners 3-Teacher [ Conners 3-T ] ) , and systematic classroom observations ( Behavioral Observation of Students in Schools [ BOSS ] ) . Paired t tests and an analysis of covariance assessed change in medication . Results : Children who received NF showed significant improvement compared with those in the control condition on the Conners 3-P Attention , Executive Functioning and Global Index , on all BRIEF summary indices , and on BOSS motor/verbal off-task behavior . Children who received CT showed no improvement compared to the control condition . Children in the NF condition showed significant improvements compared to those in the CT condition on Conners 3-P Executive Functioning , all BRIEF summary indices , SKAMP Attention , and Conners 3-T Inattention subscales . Stimulant medication dosage in methylpheni date equivalencies significantly increased for children in the CT ( 8.54 mg ) and control ( 7.05 mg ) conditions but not for those in the NF condition ( 0.29 mg ) . Conclusion : Neurofeedback made greater improvements in ADHD symptoms compared to both the control and CT conditions . Thus , NF is a promising attention training treatment intervention for children with ADHD", "In recent years a rising amount of r and omized controlled trials , review s , and meta-analyses relating to the efficacy of electroencephalographic-neurofeedback ( EEG-NF ) in children with attention-deficit/hyperactivity disorder ( ADHD ) have been published . Although clinical reports and open treatment studies suggest EEG-NF to be effective , double blind placebo-controlled studies as well as a rigorous meta- analysis failed to find support for the efficacy of EEG-NF . Since absence of evidence does not equate with evidence of absence , we will outline how future research might overcome the present method ological limitations . To provide conclusive evidence for the presence or absence of the efficacy of EEG-NF in the treatment of ADHD , there is a need to set up a well- design ed study that ensures optimal implementation and embedding of the training , and possibly incorporates different forms of neurofeedback", "BACKGROUND For children with attention deficit/hyperactivity disorder ( ADHD ) , a reduction of inattention , impulsivity and hyperactivity by neurofeedback ( NF ) has been reported in several studies . But so far , unspecific training effects have not been adequately controlled for and /or studies do not provide sufficient statistical power . To overcome these method ological shortcomings we evaluated the clinical efficacy of neurofeedback in children with ADHD in a multisite r and omised controlled study using a computerised attention skills training as a control condition . METHODS 102 children with ADHD , aged 8 to 12 years , participated in the study . Children performed either 36 sessions of NF training or a computerised attention skills training within two blocks of about four weeks each ( r and omised group assignment ) . The combined NF treatment consisted of one block of theta/beta training and one block of slow cortical potential ( SCP ) training . Pre-training , intermediate and post-training assessment encompassed several behaviour rating scales ( e.g. , the German ADHD rating scale , FBB-HKS ) completed by parents and teachers . Evaluation ( ' placebo ' ) scales were applied to control for parental expectations and satisfaction with the treatment . RESULTS For parent and teacher ratings , improvements in the NF group were superior to those of the control group . For the parent-rated FBB-HKS total score ( primary outcome measure ) , the effect size was .60 . Comparable effects were obtained for the two NF protocol s ( theta/beta training , SCP training ) . Parental attitude towards the treatment did not differ between NF and control group . CONCLUSIONS Superiority of the combined NF training indicates clinical efficacy of NF in children with ADHD . Future studies should further address the specificity of effects and how to optimise the benefit of NF as treatment module for ADHD", "Background A r and omized and controlled clinical study was performed to evaluate the use of neurofeedback ( NF ) to treat attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents . Methods The ADHD population was selected from an outpatient clinic for Child and Adolescent Mental Health in Norway . Ninety-one of the 275 children and adolescents ranging in age from 6 to 18 years ( 10.5 years ) participated in 30 sessions of an intensive NF program . The reinforcement contingency was based on the subjects ’ production of cortical beta1 activity ( 15–18 Hz ) . The ADHD participants were r and omized into three groups , with 30 in the NF group , 31 controls in a group that was given methylpheni date , and 30 in a group that received NF and methylpheni date . ADHD core symptoms were reported by parents using the parent form of the Clinician ’s Manual for Assessment by Russell A. Barkley . Results Ninety-one children and adolescents were effectively r and omized by age , sex , intelligence and distribution of ADHD core symptoms . The parents reported significant effects of the treatments , but no significant differences between the treatment groups were observed . Conclusions NF was as effective as methylpheni date at treating the attentional and hyperactivity symptoms of ADHD , based on parental reports . Trial registration Current Controlled Trials", "OBJECTIVE The purpose of this pilot study was to compare the effects of 30 sessions of neurofeedback ( NF ) with stimulant medication on attention-deficit/hyperactivity disorder ( ADHD ) patients . METHODS Thirty-two medication-naïve ADHD patients , ages 7 - 16 , from a neuropsychiatric clinic , were r and omized to NF ( n=16 ) or drug treatment ( n=16 ) . Other actions , such as parent management training , information , or support in school were given as needed , with no differences between the groups . All participants were assessed before treatment on two rating scales , each with parent and teacher forms . In addition , quantitative electroencephalogram ( QEEG ) and event-related potentials ( ERPs ) , which included behavioral data from a go/no go test were administered . NF training took place in the clinic over a period of 7 - 11 months , and was followed by a repeat of the same assessment tools . The mean time interval between pre- and postassesment was not significantly different in the two groups . The 18 symptoms of ADHD ( American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) ) were used as the primary outcome measure . RESULTS Analysis of covariance revealed a significant difference between the groups at evaluation in favor of medication , with a large effect size . This picture was confirmed by other outcome measures . The QEEG spectral power in the theta and beta b and s did not change in either group . In ERP , the P3 no go component increased significantly in 8 of 12 patients who had a clinical ly relevant medication effect , but did not increase in the medication nonresponders or the NF group . CONCLUSIONS Our study supports effects for stimulants , but not for NF . Effects of NF may require thorough patient selection , frequent training sessions , a system for excluding nonresponders , and active transfer training . The P3 no go ERP component may be a marker for treatment response", "What should be the role of P-values and confidence intervals in the interpretation of scientific results ? This question is not new 1 and our field of epidemiology is far from alone in struggling with it . 2,3 I have four suggestions for authors and readers . The first is quite broad , so I offer that one before describing current practice s. I then turn to the other three . My remarks are confined to setting s in which P-values and confidence intervals accompany estimates of effect measures , such as the relative risk . Briefly , here are my suggestions . One , we should work harder than ever to avoid strict or exact interpretations of P-values and confidence intervals in observational research , where these statistics lack a theoretical basis . Two , we should stop interpreting P-values and confidence intervals as though they measure the probability of hypotheses . Three , when we want to know the probability of hypotheses , we should use Bayesian methods , which are design ed expressly for that purpose . Four , we should get serious about precision and look for narrow confidence intervals instead of low P-values to identify results that are least influenced by r and om error", "OBJECTIVE A double-blind , r and omized , placebo-controlled study was design ed to assess the efficacy and safety of electroencephalographic ( EEG ) neurofeedback in children with attention-deficit/hyperactivity disorder ( ADHD ) . The study started in August 2008 and ended in July 2012 and was conducted at Karakter Child and Adolescent Psychiatry University Centre in Nijmegen , The Netherl and s. METHOD Forty-one children ( aged 8 - 15 years ) with a DSM-IV-TR diagnosis of ADHD were r and omly assigned to treatment with either EEG neurofeedback ( n = 22 ) or placebo neurofeedback ( n = 19 ) for 30 sessions , given as 2 sessions per week . The children were stratified by age , electrophysiologic state of arousal , and medication use . Everyone involved in the study , except the neurofeedback therapist and the principal investigator , was blinded to treatment assignment . The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV , scored at baseline , during treatment , and at study end . Clinical improvement as measured by the Clinical Global Impressions-Improvement scale ( CGI-I ) was a secondary outcome . RESULTS While total ADHD symptoms improved over time in both groups ( F1,39 = 26.56 , P clinical improvement as measured by the CGI-I ( P = .092 ) . No clinical ly relevant side effects were observed . Among the children and their parents , guessing treatment assignment was not better than chance level ( P = .224 for children , P = .643 for parents ) . CONCLUSION EEG neurofeedback was not superior to placebo neurofeedback in improving ADHD symptoms in children with ADHD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00723684", "The present study is a r and omized controlled trial that aims to evaluate the efficacy of Neurofeedback compared to st and ard pharmacological intervention in the treatment of attention deficit/hyperactivity disorder ( ADHD ) . The final sample consisted of 23 children with ADHD ( 11 boys and 12 girls , 7 - 14 years old ) . Participants carried out 40 theta/beta training sessions or received methylpheni date . Behavioral rating scales were completed by fathers , mothers , and teachers at pre- , post-treatment , two- , and six-month naturalistic follow-up . In both groups , similar significant reductions were reported in ADHD functional impairment by parents ; and in primary ADHD symptoms by parents and teachers . However , significant academic performance improvements were only detected in the Neurofeedback group . Our findings provide new evidence for the efficacy of Neurofeedback , and contribute to enlarge the range of non-pharmacological ADHD intervention choices . To our knowledge , this is the first r and omized controlled trial with a six-month follow-up that compares Neurofeedback and stimulant medication in ADHD", "PURPOSE To evaluate the efficacy of combined methylpheni date and EEG feedback treatment for children with ADHD . METHODS Forty patients with ADHD were r and omly assigned to the combination group ( methylpheni date therapy and EEG feedback training ) or control group ( methylpheni date therapy and non-feedback attention training ) in a 1:1 ratio using the double-blind method . These patients , who met the DSM-IV diagnostic criteria and were aged between 7 and 16 years , had obtained optimal therapeutic effects by titrating the methylpheni date dose prior to the trial . The patients were assessed using multiple parameters at baseline , after 20 treatment sessions , after 40 treatment sessions , and in 6-month follow-up studies . RESULTS Compared to the control group , patients in the combination group had reduced ADHD symptoms and improved in related behavioural and brain functions . CONCLUSION The combination of EEG feedback and methylpheni date treatment is more effective than methylpheni date alone . The combined therapy is especially suitable for children and adolescents with ADHD who insufficiently respond to single drug treatment or experience drug side effects", "OBJECTIVE Neurofeedback aims to reduce symptoms of attention-deficit/hyperactivity disorder ( ADHD ) , mainly attention problems . However , the additional influence of neurofeedback over treatment as usual ( TAU ) on neurocognitive functioning for adolescents with ADHD remains unclear . METHOD By using a multicenter parallel r and omized controlled trial ( RCT ) design , male adolescents with a DSM-IV-TR diagnosis of ADHD ( mean age = 16.1 years ; range , 12 - 24 ) were r and omized to receive either a combination of TAU and neurofeedback ( n = 45 ) or TAU ( n = 26 ) . R and omization was computer generated and stratified by age group ( ages 12 through 15 , 16 through 20 , and 21 through 24 years ) . The neurofeedback intervention consisted of approximately 37 sessions over a period of 25 weeks of theta/sensorimotor rhythm training on the vertex ( Cz ) . Primary neurocognitive outcomes included performance parameters derived from the D2 Test of Attention , the Digit Span backward , the Stroop Color-Word Test and the Tower of London , all assessed preintervention and postintervention . Data were collected between December 2009 and July 2012 . RESULTS At postintervention , outcomes of attention and /or motor speed were improved , with faster processing times for both intervention conditions and with medium to large effect sizes ( range , ηp2 = .08-.54 ; P values for higher executive functions were observed . Results might partly resemble practice effects . CONCLUSIONS Although neurocognitive outcomes improved in all adolescents receiving treatment for ADHD , no additional value for neurofeedback over TAU was observed . Hence , this study does not provide evidence for using theta/sensorimotor rhythm neurofeedback to enhance neurocognitive performance as additional intervention to TAU for adolescents with ADHD symptoms . TRIAL REGISTRATION Trialregister.nl identifier : 1759", "BACKGROUND The number of placebo-controlled r and omized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder ( ADHD ) is limited . For this reason , a double blind , r and omized , placebo-controlled study was design ed to assess the effects of EEG-neurofeedback on neurocognitive functioning in children with ADHD , and a systematic review on this topic was performed . METHODS Forty-one children ( 8 - 15 years ) with a DSM-IV-TR diagnosis of ADHD were r and omly allocated to EEG-neurofeedback or placebo-neurofeedback treatment for 30 sessions , twice a week . Children were stratified by age , electrophysiological state of arousal , and medication use . Neurocognitive tests of attention , executive functioning , working memory , and time processing were administered before and after treatment . Research ers , teachers , children and their parents , with the exception of the neurofeedback-therapist , were all blind to treatment assignment . Outcome measures were the changes in neurocognitive performance before and after treatment . CLINICAL TRIAL REGISTRATION www . clinical trials.gov : NCT00723684 . RESULTS No significant treatment effect on any of the neurocognitive variables was found . A systematic review of the current literature also did not find any systematic beneficial effect of EEG-neurofeedback on neurocognitive functioning . CONCLUSION Overall , the existing literature and this study fail to support any benefit of neurofeedback on neurocognitive functioning in ADHD , possibly due to small sample sizes and other study limitations", "In a r and omized controlled trial , neurofeedback ( NF ) training was found to be superior to a computerised attention skills training concerning the reduction of ADHD symptomatology ( Gevensleben et al. , 2009 ) . The aims of this investigation were to assess the impact of different NF protocol s ( theta/beta training and training of slow cortical potentials , SCPs ) on the resting EEG and the association between distinct EEG measures and behavioral improvements . In 72 ( of initially 102 ) children with ADHD , aged 8 - 12 , EEG changes after either a NF training ( n=46 ) or the control training ( n=26 ) could be studied . The combined NF training consisted of one block of theta/beta training and one block of SCP training , each block comprising 18 units of 50 minutes ( balanced order ) . Spontaneous EEG was recorded in a two-minute resting condition before the start of the training , between the two training blocks and after the end of the training . Activity in the different EEG frequency b and s was analyzed . In contrast to the control condition , the combined NF training was accompanied by a reduction of theta activity . Protocol -specific EEG changes ( theta/beta training : decrease of posterior-midline theta activity ; SCP training : increase of central -midline alpha activity ) were associated with improvements in the German ADHD rating scale . Related EEG-based predictors were obtained . Thus , differential EEG patterns for theta/beta and SCP training provide further evidence that distinct neuronal mechanisms may contribute to similar behavioral improvements in children with ADHD", "Objective . This study examined the efficacy of 2 computer-based training systems to teach children with attention deficit/hyperactivity disorder ( ADHD ) to attend more effectively . Design / methods . A total of 41 children with ADHD from 2 middle schools were r and omly assigned to receive 2 sessions a week at school of either neurofeedback ( NF ) or attention training through a st and ard computer format ( SCF ) , either immediately or after a 6-month wait ( waitlist control group ) . Parents , children , and teachers completed question naires pre- and postintervention . Results . Primary parents in the NF condition reported significant ( P Conners ’s Rating Scales — Revised ( CRS-R ) and Behavior Assessment Scales for Children ( BASC ) subscales ; and in the SCF condition , they reported significant ( P the CRS-R Inattention scale and ADHD index , the BASC Attention Problems Scale , and on the Behavioral Rating Inventory of Executive Functioning ( BRIEF ) . Conclusion . This r and omized control trial provides preliminary evidence of the effectiveness of computer-based interventions for ADHD and supports the feasibility of offering them in a school setting", "BACKGROUND Recent electrophysiologic studies have found fairly consistent differences between children with attention-deficit/hyperactivity disorder ( ADHD ) and age-matched control subjects . The present study examined electroencephalogram ( EEG ) changes associated with a double blind , placebo-controlled administration of methylpheni date among children with ADHD . METHODS Subjects were 10 children , ages 8 to 13 , with a primary diagnosis of ADHD . Brain electrical activity was recorded with 7 electrodes in the frontal , central , and midline areas during baseline and cognitive activation conditions . RESULTS Repeated- measures ANOVAs indicate that children exhibiting a positive medication response had reductions of theta and alpha as well as increased beta in the frontal regions , while nonresponders showed the opposite pattern ( p a vigilance task and changes in beta activity in the frontal electrodes emerged as well . CONCLUSIONS These preliminary findings indicate that there are different electrophysiologic correlates to methylpheni date among ADHD children who are medication responders and nonresponders" ]

[ "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 .", "Aims To compare the efficacy [ low-density lipoprotein cholesterol ( LDL-C ) lowering ] and safety of alirocumab , a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9 , compared with ezetimibe , as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia . Methods and results COMBO II is a double-blind , double-dummy , active-controlled , parallel-group , 104-week study of alirocumab vs. ezetimibe . Patients ( n = 720 ) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled ( August 2012–May 2013 ) . This pre-specified analysis was conducted after the last patient completed 52 weeks . Patients were r and omized to subcutaneous alirocumab 75 mg every 2 weeks ( plus oral placebo ) or oral ezetimibe 10 mg daily ( plus subcutaneous placebo ) on a background of statin therapy . At Week 24 , mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4 % for alirocumab vs. 20.7 ± 1.9 % for ezetimibe ( difference 29.8 ± 2.3 % ; P % of alirocumab and 45.6 % of ezetimibe patients achieved LDL-C LDL-C at Week 24 was 1.3 ± 0.04 mmol/L with alirocumab and 2.1 ± 0.05 mmol/L with ezetimibe , and were maintained to Week 52 . Alirocumab was generally well tolerated , with no evidence of an excess of treatment-emergent adverse events . Conclusion In patients at high cardiovascular risk with inadequately controlled LDL-C , alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe , with a similar safety profile . Trial registration clinical trials.gov Identifier : NCT01644188", "Abstract Aims The objective of this study was to evaluate the efficacy , safety , and tolerability of LY3015014 ( LY ) , a neutralizing antibody of proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , administered every 4 or 8 weeks in patients with primary hypercholesterolaemia , when added to a background of st and ard-of-care lipid-lowering therapy , including statins . Methods and results Double-blind , placebo-controlled trial r and omized 527 patients with primary hypercholesterolaemia from June 2013 to January 2014 at 61 community and academic centres in North America , Europe , and Japan . Patients were r and omized to subcutaneous injections of LY 20 , 120 , or 300 mg every 4 weeks ( Q4W ) ; 100 or 300 mg every 8 weeks ( Q8W ) alternating with placebo Q4W ; or placebo Q4W . The primary endpoint was percentage change from baseline in low-density lipoprotein cholesterol ( LDL-C ) by beta quantification at Week 16 . The mean baseline LDL-C by beta quantification was 136.3 ( SD , 45.0)mg/dL. LY3015014 dose-dependently decreased LDL-C , with a maximal reduction of 50.5 % with 300 mg LY Q4W and 37.1 % with 300 mg LY Q8W compared with a 7.6 % increase with placebo maintained at the end of the dosing interval . There were no treatment-related serious adverse events ( AEs ) . The most common AE terms ( > 10 % of any treatment group ) reported more frequently with LY compared with placebo were injection site ( IS ) pain and IS erythema . No liver or muscle safety issues emerged . Conclusions LY3015014 dosed every 4 or 8 weeks , result ed in robust and durable reductions in LDL-C. No clinical ly relevant safety issues emerged with the administration of LY . The long-term effects on cardiovascular outcomes require further investigation", "BACKGROUND Inhibition of proprotein convertase subtilisin/kexin type 9 serine protease ( PCSK9 ) result ed in large reductions of low-density lipoprotein cholesterol ( LDL-C ) in phase 1 trials . We assessed the efficacy and safety of various doses and dosing intervals of REGN727 , a monoclonal antibody to PCSK9 , added to statins , to further lower LDL-C in patients with heterozygous familial hypercholesterolaemia . METHODS This multicentre , r and omised , placebo-controlled phase 2 trial was done at 16 lipid clinics in the USA and Canada . Between Jan 18 , 2011 , and Nov 7 , 2011 , we enrolled adults with heterozygous familial hypercholesterolaemia and LDL-C concentrations of 2·6 mmol/L or higher on stable diet and statin dose , with or without ezetimibe . Patients were r and omly assigned to receive REGN727 150 mg , 200 mg , or 300 mg every 4 weeks , or 150 mg every 2 weeks , or placebo every 2 weeks ( ratio 1:1:1:1:1 ) . R and omisation was stratified by concomitant use of ezetimibe at baseline . Investigators , study staff , and patients were masked to treatment group . Blinding was maintained by administration of placebo alternating with REGN727 for the groups of 4 week dosing . The primary endpoint was mean percent reduction in LDL-C from baseline at week 12 and was analysed in the modified intention-to-treat population with an analysis of covariance ( ANCOVA ) model with treatment group . This trial is registered in Clinical Trials.gov , number NCT 01266876 . FINDINGS 77 patients were r and omly assigned to study groups ( 15 - 16 patients per group ) and all were analysed . Least-squares ( LS ) mean LDL-C reduction from baseline to week 12 was 28·9 % ( SE 5·08 ) for 150 mg every 4 weeks ( p=0·0113 ) , 31·54 % ( 4·91 ) for 200 mg every 4 weeks ( p=0·0035 ) , 42·53 % ( 5·09 ) for 300 mg every 4 weeks ( p ) with placebo . One serious adverse event was reported with placebo and none with REGN727 . No increases of more than three times the upper limit of normal were reported for hepatic transaminases or creatinine kinase . The most common adverse event was injection-site reaction with one patient in the group of 300 mg REGN727 terminating treatment . INTERPRETATION REGN727 was well tolerated and achieved substantial further LDL-C reduction in patients with heterozygous familial hypercholesterolaemia and elevated LDL-C treated with high-dose statins , with or without ezetimibe . REGN727 has the potential to provide optimum control of LDL-C in patients with this disorder . FUNDING Sanofi US and Regeneron Pharmaceuticals Incorporated", "AIMS Proprotein convertase subtilisin kexin 9 ( PCSK9 ) is an emerging target for the treatment of hypercholesterolaemia , but the clinical utility of PCSK9 levels to guide treatment is unknown . We aim ed to prospect ively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes ( ACS ) . METHODS AND RESULTS Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospect i ve cohort . At 1 year , the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events ( GRACE ) variables , as well as the achievement of LDL cholesterol targets of Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia ( rate ratio , RR 1.21 , 95 % confidence interval , CI 1.09 - 1.53 ) , be treated with lipid-lowering therapy ( RR 1.46 , 95 % CI 1.30 - 1.63 ) , present with longer time interval of chest pain ( RR 1.29 , 95 % CI 1.09 - 1.53 ) and higher C-reactive protein levels ( RR 1.22 , 95 % CI 1.16 - 1.30 ) . PCSK9 increased 12 - 24 h after ACS ( 374 ± 149 vs. 323 ± 134 ng/mL , P PCSK9-level tertiles were 1.13 ( 95 % CI 0.69 - 1.85 ) for all-cause death and remained similar after adjustment for the GRACE score . Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets ( RR 0.81 , 95 % CI 0.66 - 0.99 ) . CONCLUSION In ACS patients , high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia , but did not predict mortality at 1 year", "BACKGROUND Inflammation plays a fundamental role in atherothrombosis . Yet , whether direct inhibition of inflammation will reduce the occurrence of adverse cardiovascular outcomes is not known . DESIGN The Cardiovascular Inflammation Reduction Trial ( CIRT ) ( Clinical Trials.govNCT01594333 ) will r and omly allocate 7,000 patients with prior myocardial infa rct ion ( MI ) and either type 2 diabetes or the metabolic syndrome to low-dose methotrexate ( target dose 15 - 20 mg/wk ) or placebo over an average follow-up period of 3 to 5 years . Low-dose methotrexate is a commonly used anti-inflammatory regimen for the treatment of rheumatoid arthritis and lacks significant effects on lipid levels , blood pressure , or platelet function . Both observational and mechanistic studies suggest that low-dose methotrexate has clinical ly relevant antiatherothrombotic effects . The CIRT primary end point is a composite of nonfatal MI , nonfatal stroke , and cardiovascular death . Secondary end points are all-cause mortality , coronary revascularization plus the primary end point , hospitalization for congestive heart failure plus the primary end point , all-cause mortality plus coronary revascularization plus congestive heart failure plus the primary end point , incident type 2 diabetes , and net clinical benefit or harm . CIRT will use st and ardized central methodology design ed to ensure consistent performance of all dose adjustments and safety interventions at each clinical site in a manner that protects the blinding to treatment but maintains safety for enrolled participants . SUMMARY CIRT aims to test the inflammatory hypothesis of atherothrombosis in patients with prior MI and either type 2 diabetes or metabolic syndrome , conditions associated with persistent inflammation . If low-dose methotrexate reduces cardiovascular events , CIRT would provide a novel therapeutic approach for the secondary prevention of heart attack , stroke , and cardiovascular death", "BACKGROUND Evolocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , significantly reduced low-density lipoprotein ( LDL ) cholesterol levels in phase 2 studies . We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab . METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program . On the basis of this classification , patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily , atorvastatin at a dose of 80 mg daily , or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily , for a run-in period of 4 to 12 weeks . Patients with an LDL cholesterol level of 75 mg per deciliter ( 1.9 mmol per liter ) or higher were then r and omly assigned in a 2:1 ratio to receive either evolocumab ( 420 mg ) or placebo every 4 weeks . The primary end point was the percent change from baseline in LDL cholesterol , as measured by means of ultracentrifugation , at week 52 . RESULTS Among the 901 patients included in the primary analysis , the overall least-squares mean ( ±SE ) reduction in LDL cholesterol from baseline in the evolocumab group , taking into account the change in the placebo group , was 57.0±2.1 % ( P atorvastatin , and 48.5±5.2 % among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe ( P comparisons ) . Evolocumab treatment also significantly reduced levels of apolipoprotein B , non-high-density lipoprotein cholesterol , lipoprotein(a ) , and triglycerides . The most common adverse events were nasopharyngitis , upper respiratory tract infection , influenza , and back pain . CONCLUSIONS At 52 weeks , evolocumab added to diet alone , to low-dose atorvastatin , or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks . ( Funded by Amgen ; DESCARTES Clinical Trials.gov number , NCT01516879 . )", "BACKGROUND Inflammation may be important in the pathogenesis of atherothrombosis . We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk . METHODS We measured plasma C-reactive protein , a marker for systemic inflammation , in 543 apparently healthy men participating in the Physicians ' Health Study in whom myocardial infa rct ion , stroke , or venous thrombosis subsequently developed , and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years . Subjects were r and omly assigned to receive aspirin or placebo at the beginning of the trial . RESULTS Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infa rct ion ( 1.51 vs. 1.13 mg per liter , P C-reactive protein values had three times the risk of myocardial infa rct ion ( relative risk , 2.9 ; P risk of ischemic stroke ( relative risk , 1.9 ; P=0.02 ) of the men in the lowest quartile . Risks were stable over long periods , were not modified by smoking , and were independent of other lipid-related and non-lipid-related risk factors . The use of aspirin was associated with significant reductions in the risk of myocardial infa rct ion ( 55.7 percent reduction , P=0.02 ) among men in the highest quartile but with only small , nonsignificant reductions among those in the lowest quartile ( 13.9 percent , P=0.77 ) . CONCLUSIONS The base-line plasma concentration of C-reactive protein predicts the risk of future myocardial infa rct ion and stroke . Moreover , the reduction associated with the use of aspirin in the risk of a first myocardial infa rct ion appears to be directly related to the level of C-reactive protein , raising the possibility that antiinflammatory agents may have clinical benefits in preventing cardiovascular disease", "Atherosclerosis is currently considered a chronic inflammatory disease of the vessel wall . Systemic markers of inflammation have been shown to be of significant prognostic relevance for assessing the risk of atherosclerotic disease progression (1)(2)(3)(4 ) . Previous data showed that proinflammatory markers , such as C-reactive protein ( CRP ) , play an important role in acute coronary events (5)(6)(7 ) and that decreased plasma concentrations of antiinflammatory cytokines , for example , interleukin-10 ( IL-10 ) were also associated with acute coronary syndrome ( ACS ) (8)(9)(10 ) . Statins , 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors , represent a well-established class of drugs that effectively lower serum cholesterol concentrations and are widely used for the treatment of cardiovascular disease (11)(12)(13 ) . In addition to their cholesterol-lowering activity , statins have been demonstrated to possess pleiotropic effects , including antiinflammatory effects (14)(15)(16)(17 ) . Results obtained in numerous investigations have suggested that administration of statins could modify concentrations of CRP and other proinflammatory cytokines with a concurrent decrease in cardiovascular events . However , the potential influence of statins on the antiinflammatory cytokine IL-10 in patients with ACS has not been investigated . In the present study , 42 patients with unstable angina ( UA ) were r and omly assigned immediately after admission to st and ard therapy plus either 20 mg/day atorvastatin or placebo . The st and ard therapy included aspirin , beta-blockers , heparin/low – molecular-weight heparin , angiotensin-converting enzyme inhibitors , and oral nitrates . The protocol s of the study were approved by the Ethics Review Board of the Hospital , and all patients gave written , informed consent . The patients with UA presented with ischemic chest pain at rest in the absence of extracardiac cause with ST-segment depression ≥0.1 mV in 2 or more contiguous leads on 12-lead electrocardiograms at administration . Echocardiography was performed in all patients to exclude patients with an impaired left", "BACKGROUND Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol , increased plasma LDL cholesterol concentrations , and premature cardiovascular disease . Despite intensive statin therapy , with or without ezetimibe , many patients are unable to achieve recommended target levels of LDL cholesterol . We investigated the effect of PCSK9 inhibition with evolocumab ( AMG 145 ) on LDL cholesterol in patients with this disorder . METHODS This multicentre , r and omised , double-blind , placebo-controlled trial was undertaken at 39 sites ( most of which were specialised lipid clinics , mainly attached to academic institutions ) in Australia , Asia , Europe , New Zeal and , North America , and South Africa between Feb 7 and Dec 19 , 2013 . 331 eligible patients ( 18 - 80 years of age ) , who met clinical criteria for heterozygous familial hypercholesterolaemia and were on stable lipid-lowering therapy for at least 4 weeks , with a fasting LDL cholesterol concentration of 2·6 mmol/L or higher , were r and omly allocated in a 2:2:1:1 ratio to receive subcutaneous evolocumab 140 mg every 2 weeks , evolocumab 420 mg monthly , or subcutaneous placebo every 2 weeks or monthly for 12 weeks . R and omisation was computer generated by the study sponsor , implemented by a computerised voice interactive system , and stratified by LDL cholesterol concentration at screening ( higher or lower than 4·1 mmol/L ) and by baseline ezetimibe use ( yes/no ) . Patients , study personnel , investigators , and Amgen study staff were masked to treatment assignments within dosing frequency groups . The co primary endpoints were percentage change from baseline in LDL cholesterol at week 12 and at the mean of weeks 10 and 12 , analysed by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT01763918 . FINDINGS Of 415 screened patients , 331 were eligible and were r and omly assigned to the four treatment groups : evolocumab 140 mg every 2 weeks ( n=111 ) , evolocumab 420 mg monthly ( n=110 ) , placebo every 2 weeks ( n=55 ) , or placebo monthly ( n=55 ) . 329 patients received at least one dose of study drug . Compared with placebo , evolocumab at both dosing schedules led to a significant reduction in mean LDL cholesterol at week 12 ( every-2-weeks dose : 59·2 % reduction [ 95 % CI 53·4 - 65·1 ] , monthly dose : 61·3 % reduction [ 53·6 - 69·0 ] ; both p ] ; both p ) . Evolocumab was well tolerated , with rates of adverse events similar to placebo . The most common adverse events occurring more frequently in the evolocumab-treated patients than in the placebo groups were nasopharyngitis ( in 19 patients [ 9 % ] vs five [ 5 % ] in the placebo group ) and muscle-related adverse events ( ten patients [ 5 % ] vs 1 [ 1 % ] ) . INTERPRETATION In patients with heterozygous familial hypercholesterolaemia , evolocumab administered either 140 mg every 2 weeks or 420 mg monthly was well tolerated and yielded similar and rapid 60 % reductions in LDL cholesterol compared with placebo . FUNDING Amgen", "BACKGROUND Homozygous familial hypercholesterolaemia is a rare , serious disorder caused by very low or absent plasma clearance of LDL , substantially raised LDL cholesterol , and accelerated development of cardiovascular disease . Conventional lipid-lowering treatments are modestly effective . Evolocumab , a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , reduced LDL cholesterol by 16 % in a pilot study . We now report results with evolocumab in a r and omised , double-blind , placebo-controlled phase 3 trial . METHODS This r and omised , double-blind , placebo-controlled phase 3 trial was undertaken at 17 sites in ten countries in North America , Europe , the Middle East , and South Africa . 50 eligible patients ( aged ≥12 years ) with homozygous familial hypercholesterolaemia , on stable lipid-regulating therapy for at least 4 weeks , and not receiving lipoprotein apheresis , were r and omly allocated by a computer-generated r and omisation sequence in a 2:1 ratio to receive subcutaneous evolocumab 420 mg or placebo every 4 weeks for 12 weeks . R and omisation was stratified by LDL cholesterol at screening ( computerised interactive voice-response system . Patients , study personnel , and the funder were masked to treatment and to the efficacy results by the central laboratory not returning LDL cholesterol or any lipid results to the clinical sites after the baseline visit . The primary endpoint was percentage change in ultracentrifugation LDL cholesterol from baseline at week 12 compared with placebo , analysed by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT01588496 . FINDINGS Of the 50 eligible patients r and omly assigned to the two treatment groups , 49 actually received the study drug and completed the study ( 16 in the placebo group and 33 in the evolocumab group ) . Compared with placebo , evolocumab significantly reduced ultracentrifugation LDL cholesterol at 12 weeks by 30·9 % ( 95 % CI -43·9 % to -18·0 % ; p events occurred in ten ( 63 % ) of 16 patients in the placebo group and 12 ( 36 % ) of 33 in the evolocumab group . No serious clinical or laboratory adverse events occurred , and no anti-evolocumab antibody development was detected during the study . INTERPRETATION In patients with homozygous familial hypercholesterolaemia receiving stable background lipid-lowering treatment and not on apheresis , evolocumab 420 mg administered every 4 weeks was well tolerated and significantly reduced LDL cholesterol compared with placebo . FUNDING Amgen", "Importance Reducing levels of low-density lipoprotein cholesterol ( LDL-C ) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels . Proprotein convertase subtilisin kexin type 9 ( PCSK9 ) inhibitors produce incremental LDL-C lowering in statin-treated patients ; however , the effects of these drugs on coronary atherosclerosis have not been evaluated . Objective To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients . Design , Setting , and Participants The GLAGOV multicenter , double-blind , placebo-controlled , r and omized clinical trial ( enrollment May 3 , 2013 , to January 12 , 2015 ) conducted at 197 academic and community hospitals in North America , Europe , South America , Asia , Australia , and South Africa and enrolling 968 patients presenting for coronary angiography . Interventions Participants with angiographic coronary disease were r and omized to receive monthly evolocumab ( 420 mg ) ( n = 484 ) or placebo ( n = 484 ) via subcutaneous injection for 76 weeks , in addition to statins . Main Outcomes and Measures The primary efficacy measure was the nominal change in percent atheroma volume ( PAV ) from baseline to week 78 , measured by serial intravascular ultrasonography ( IVUS ) imaging . Secondary efficacy measures were nominal change in normalized total atheroma volume ( TAV ) and percentage of patients demonstrating plaque regression . Safety and tolerability were also evaluated . Results Among the 968 treated patients ( mean age , 59.8 years [ SD , 9.2 ] ; 269 [ 27.8 % ] women ; mean LDL-C level , 92.5 mg/dL [ SD , 27.2 ] ) , 846 had evaluable imaging at follow-up . Compared with placebo , the evolocumab group achieved lower mean , time-weighted LDL-C levels ( 93.0 vs 36.6 mg/dL ; difference , -56.5 mg/dL [ 95 % CI , -59.7 to -53.4 ] ; P PAV , increased 0.05 % with placebo and decreased 0.95 % with evolocumab ( difference , -1.0 % [ 95 % CI , -1.8 % to -0.64 % ] ; P evolocumab ( difference , -4.9 mm3 [ 95 % CI , -7.3 to -2.5 ] ; P . Evolocumab induced plaque regression in a greater percentage of patients than placebo ( 64.3 % vs 47.3 % ; difference , 17.0 % [ 95 % CI , 10.4 % to 23.6 % ] ; P patients with angiographic coronary disease treated with statins , addition of evolocumab , compared with placebo , result ed in a greater decrease in PAV after 76 weeks of treatment . Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes . Trial Registration clinical trials.gov Identifier : NCT01813422", "BACKGROUND Serum proprotein convertase subtilisin/kexin 9 ( PCSK9 ) binds to low-density lipoprotein ( LDL ) receptors , increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation . REGN727/SAR236553 ( design ated here as SAR236553 ) , a fully human PCSK9 monoclonal antibody , increases the recycling of LDL receptors and reduces LDL cholesterol levels . METHODS We performed a phase 2 , multicenter , double-blind , placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter ( 2.6 mmol per liter ) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks . Patients were r and omly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks , 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks , or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment . RESULTS The least-squares mean ( ±SE ) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553 , as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo ( P mg of atorvastatin plus SAR236553 . All the patients who received SAR236553 , as compared with 52 % of those who received 80 mg of atorvastatin plus placebo , attained an LDL cholesterol level of less than 100 mg per deciliter , and at least 90 % of the patients who received SAR236553 , as compared with 17 % who received 80 mg of atorvastatin plus placebo , attained LDL cholesterol levels of less than 70 mg per deciliter ( 1.8 mmol per liter ) . CONCLUSIONS In a r and omized trial involving patients with primary hypercholesterolemia , adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin result ed in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone . ( Funded by Sanofi and Regeneron Pharmaceuticals ; Clinical Trials.gov number , NCT01288469 . )", "BACKGROUND Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease . Yet , the inflammatory hypothesis of atherothrombosis has remained unproved . METHODS We conducted a r and omized , double‐blind trial of canakinumab , a therapeutic monoclonal antibody targeting interleukin‐1β , involving 10,061 patients with previous myocardial infa rct ion and a high‐sensitivity C‐reactive protein level of 2 mg or more per liter . The trial compared three doses of canakinumab ( 50 mg , 150 mg , and 300 mg , administered subcutaneously every 3 months ) with placebo . The primary efficacy end point was nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death . RESULTS At 48 months , the median reduction from baseline in the high‐sensitivity C‐reactive protein level was 26 percentage points greater in the group that received the 50‐mg dose of canakinumab , 37 percentage points greater in the 150‐mg group , and 41 percentage points greater in the 300‐mg group than in the placebo group . Canakinumab did not reduce lipid levels from baseline . At a median follow‐up of 3.7 years , the incidence rate for the primary end point was 4.50 events per 100 person‐years in the placebo group , 4.11 events per 100 person‐years in the 50‐mg group , 3.86 events per 100 person‐years in the 150‐mg group , and 3.90 events per 100 person‐years in the 300‐mg group . The hazard ratios as compared with placebo were as follows : in the 50‐mg group , 0.93 ( 95 % confidence interval [ CI ] , 0.80 to 1.07 ; P=0.30 ) ; in the 150‐mg group , 0.85 ( 95 % CI , 0.74 to 0.98 ; P=0.021 ) ; and in the 300‐mg group , 0.86 ( 95 % CI , 0.75 to 0.99 ; P=0.031 ) . The 150‐mg dose , but not the other doses , met the prespecified multiplicity‐adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization ( hazard ratio vs. placebo , 0.83 ; 95 % CI , 0.73 to 0.95 ; P=0.005 ) . Canakinumab was associated with a higher incidence of fatal infection than was placebo . There was no significant difference in all‐cause mortality ( hazard ratio for all canakinumab doses vs. placebo , 0.94 ; 95 % CI , 0.83 to 1.06 ; P=0.31 ) . CONCLUSIONS Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo , independent of lipid‐level lowering . ( Funded by Novartis ; CANTOS Clinical Trials.gov number , NCT01327846 .", "RG7652 ( MPSK3169A ) , a fully human immunoglobulin G1 ( IgG1 ) monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , blocks the interaction between PCSK9 and low-density lipoprotein ( LDL ) receptor . EQUATOR ( Clinical Trials.govNCT01609140 ) , a r and omized , double-blind , and dose-ranging phase 2 study , evaluated RG7652 in patients ( 1 ) at high risk for or ( 2 ) with coronary heart disease ( CHD ) . The primary end point was change in LDL cholesterol ( LDL-C ) from baseline to day 169 . Patients ( n = 248 ; median age , 64 years ; 57 % men ; 52 % with established CHD ; 82 % on statins ) with baseline LDL-C levels of 90 to 250 mg/dl ( mean , 126 mg/dl ) continuing on st and ard-of-care therapy were r and omized to receive 1 of 5 RG7652 doses or placebo , subcutaneously every 4 , 8 , or 12 weeks for 24 weeks . Significant dose-dependent reductions in LDL-C levels from baseline to nadir ( 56 to 74 mg/dl [ 48 % to 60 % ] ) were observed in all RG7652-dosed patients ; effects persisted to day 169 with the highest doses ( reduction vs placebo up to 62 mg/dl [ 51 % ] ) with no unexpected safety signals . RG7652 reduced apolipoprotein B and lipoprotein(a ) levels . LDL-C subfraction analysis by nuclear magnetic resonance spectroscopy revealed a prominent decrease in large LDL-C and some decrease in small LDL particles . There was significant reduction in mean particle size of LDL-C on day 169 but no significant reductions in systemic markers of inflammation ( high-sensitivity C-reactive protein , interleukin-6 , and tumor necrosis factor-alpha ) . RG7652 reduced LDL-C levels and was well tolerated in patients at high risk for or with CHD on st and ard-of-care therapy . In conclusion , RG7562 treatment affected large LDL-C and , to a lesser extent , small LDL-C particles ; RG7562 did not affect systemic circulating pro-inflammatory cytokines or high-sensitivity C-reactive protein", "OBJECTIVES This study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin doses . BACKGROUND Statin intolerance , which is predominantly due to muscle-related side effects , is reported in up to 10 % to 20 % of patients . Evolocumab , a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , demonstrated marked reductions in plasma low-density lipoprotein cholesterol ( LDL-C ) in a phase 2 study in statin-intolerant patients . METHODS The GAUSS-2 ( Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects ) trial was a 12-week , double-blind study of r and omized patients ( 2:2:1:1 ) to evolocumab 140 mg every two weeks ( Q2W ) or evolocumab 420 mg once monthly ( QM ) both with daily oral placebo or subcutaneous placebo Q2W or QM both with daily oral ezetimibe 10 mg . Co- primary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12 , and at week 12 . RESULTS Three hundred seven patients ( age 62 ± 10 years ; LDL-C 193 ± 59 mg/dl ) were r and omized . Evolocumab reduced LDL-C from baseline by 53 % to 56 % , corresponding to treatment differences versus ezetimibe of 37 % to 39 % ( p occurred in 12 % of evolocumab-treated patients and 23 % of ezetimibe-treated patients . Treatment-emergent adverse events and laboratory abnormalities were comparable across treatment groups . CONCLUSIONS Robust efficacy combined with favorable tolerability makes evolocumab a promising therapy for addressing the largely unmet clinical need in high-risk patients with elevated cholesterol who are statin intolerant . ( Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2 ; NCT01763905 )", "Abstract Aim . To evaluate the relation of proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) levels to coronary artery disease ( CAD ) . Methods . A total of 1031 consecutive individuals ( 552 CAD and 479 controls ) were prospect ively enrolled . The associations of plasma PCSK9 levels with the incidence and severity of CAD were investigated . Further , mediator analysis was performed to detect the potential mechanisms of the associations . Results . No difference in PCSK9 levels between CAD patients and controls was detected ( median 224.75 versus 224.64 ng/mL , P > 0.05 ) . However , the CAD group had higher PCSK9 levels than the control group when adjusting for the confounding factors ( 228.03 ± 1.01 versus 219.28 ± 1.02 ng/mL , P = 0.019 ) . PCSK9 levels were also associated with the severity of CAD assessed by the Gensini score ( GS ) system ( P for trend that PCSK9 levels were associated with an increased CAD risk ( OR 3.296 and 5.130 for the incidence and severity , respectively ) . Importantly , mediator analysis indicated that the effects of PCSK9 levels on CAD were mediated by lipid ( around 20 % ) and inflammation ( around 15 % ) . Conclusions . PCSK9 levels were positively associated with the severity of CAD ; the relatively important mechanisms including lipid and inflammation pathways were partly involved in this association", "Background — Despite statin treatment , many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol ( LDL-C ) targets . AMG 145 , a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) serine protease , demonstrated significant reductions in LDL-C in phase 1 studies . This phase 2 , multicenter , double-blind , r and omized , placebo-controlled , dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients . Methods and Results — Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L ( 100 mg/dL ) despite statin therapy with or without ezetimibe were r and omized 1:1:1 to AMG 145 350 mg , AMG 145 420 mg , or placebo-administered subcutaneously every 4 weeks . The primary end point was percentage change from baseline in LDL-C at week 12 . Of 168 patients r and omized , 167 received investigational product and were included in the full analysis set ( mean [ SD ] age , 50 [ 13 ] years ; 47 % female ; 89 % white ; mean [ SD ] baseline LDL-C , 4.0 [ 1.1 ] mmol/L ( 156 [ 42 ] mg/dL ) ) . At week 12 , LDL-C reduction measured by preparative ultracentrifugation ( least squares mean [ st and ard error ( SE ) ] ) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420 mg , respectively , compared with 1 (3)% increase with placebo ( P ) . Serious adverse events ( not considered treatment-related ) occurred in 2 patients on AMG 145 . Conclusions — AMG 145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use , with or without ezetimibe , with minimal adverse events and good tolerability . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01375751" ]

[ "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", "BACKGROUND Multiple organ dysfunction syndrome ( MODS ) is a major cause of mortality in intensive care units . A breakdown in gut barrier function and immune dysfunction are associated with the onset of MODS . Probiotic bacteria have been shown to modulate intestinal barrier and immune function . OBJECTIVE This study assessed the efficacy of a probiotic compound in a viable and nonviable formulation in modulating intestinal permeability and immune function and preventing the onset of MODS in patients in the intensive care unit . DESIGN A double-blind , r and omized controlled trial was conducted in the intensive care unit of a tertiary care teaching hospital . Twenty-eight critically ill patients admitted to the intensive care unit were r and omly assigned to receive 1 of 3 treatments daily for 7 d : 1 ) placebo , 2 ) viable probiotics , or 3 ) equivalent probiotic sonicates . MODS scores and systemic concentrations of immunoglobulin ( Ig ) A and IgG were measured on days -1 , 4 , and 7 , and intestinal permeability measurements were taken daily . RESULTS The patients responded to viable probiotics with a significantly larger increase in systemic IgA and IgG concentrations than in the patients who received placebo or sonicates ( P MODS scores were not significantly affected by probiotic treatment . Over the study period , intestinal permeability decreased in most patients . CONCLUSION Patients receiving viable probiotics show a greater enhancement in immune activity than do patients receiving either placebo or probiotic bacterial sonicates", "BACKGROUND & AIMS Probiotics can reduce symptoms of irritable bowel syndrome ( IBS ) , but little is known about their effects on psychiatric comorbidities . We performed a prospect i ve study to evaluate the effects of Bifidobacterium longum NCC3001 ( BL ) on anxiety and depression in patients with IBS . METHODS We performed a r and omized , double-blind , placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern ( based on Rome III criteria ) and mild to moderate anxiety and /or depression ( based on the Hospital Anxiety and Depression scale ) at McMaster University in Canada , from March 2011 to May 2014 . At the screening visit , clinical history and symptoms were assessed and blood sample s were collected . Patients were then r and omly assigned to groups and given daily BL ( n = 22 ) or placebo ( n = 22 ) for 6 weeks . At weeks 0 , 6 , and 10 , we determined patients ' levels of anxiety and depression , IBS symptoms , quality of life , and somatization using vali date d question naires . At weeks 0 and 6 , stool , urine and blood sample s were collected , and functional magnetic resonance imaging ( fMRI ) test was performed . We assessed brain activation patterns , fecal microbiota , urine metabolome profiles , serum markers of inflammation , neurotransmitters , and neurotrophin levels . RESULTS At week 6 , 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale , vs 7 of 22 patients in the placebo group ( P = .04 ) . BL had no significant effect on anxiety or IBS symptoms . Patients in the BL group had a mean increase in quality of life score compared with the placebo group . The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas , including amygdala and fronto-limbic regions , compared with placebo . The groups had similar fecal microbiota profiles , serum markers of inflammation , and levels of neurotrophins and neurotransmitters , but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites . At week 10 , depression scores were reduced in patients given BL vs placebo . CONCLUSION In a placebo-controlled trial , we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS . These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity . Clinical Trials.gov no. NCT01276626", "According to animal studies , intake of probiotic bacteria may improve glucose homeostasis . We hypothesised that probiotic bacteria improve insulin sensitivity by attenuating systemic inflammation . Therefore , the effects of oral supplementation with the probiotic bacterium Lactobacillus acidophilus NCFM on insulin sensitivity and the inflammatory response were investigated in subjects with normal or impaired insulin sensitivity . In a double-blinded , r and omised fashion , forty-five males with type 2 diabetes , impaired or normal glucose tolerance were enrolled and allocated to a 4-week treatment course with either L. acidophilus NCFM or placebo . L. acidophilus was detected in stool sample s by denaturating gradient gel electrophoresis and real-time PCR . Separated by the 4-week intervention period , two hyperinsulinaemic-euglycaemic clamps were performed to estimate insulin sensitivity . Furthermore , the systemic inflammatory response was evaluated by subjecting the participants to Escherichia coli lipopolysaccharide injection ( 0·3 ng/kg ) before and after the treatment course . L. acidophilus NCFM was detected in 75 % of the faecal sample s after treatment with the probiotic bacterium . Insulin sensitivity was preserved among volunteers in the L. acidophilus NCFM group , whereas it decreased in the placebo group . Both baseline inflammatory markers and the systemic inflammatory response were , however , unaffected by the intervention . In conclusion , intake of L. acidophilus NCFM for 4 weeks preserved insulin sensitivity compared with placebo , but did not affect the systemic inflammatory response ", "Aim Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing . However , the effect of multi-strain probiotics in people with type 2 diabetes remains unclear . This study investigated the effect of multi-strain microbial cell preparation — also refers to multi-strain probiotics — on glycemic control and other diabetes-related outcomes in people with type 2 diabetes . Design A r and omized , double-blind , parallel-group , controlled clinical trial . Setting Diabetes clinic of a teaching hospital in Kuala Lumpur , Malaysia . Participants A total of 136 participants with type 2 diabetes , aged 30–70 years , were recruited and r and omly assigned to receive either probiotics ( n = 68 ) or placebo ( n = 68 ) for 12 weeks . Outcomes Primary outcomes were glycemic control-related parameters , and secondary outcomes were anthropomorphic variables , lipid profile , blood pressure and high-sensitivity C-reactive protein . The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract . Statistical analysis Intention-to-treat ( ITT ) analysis was performed on all participants , while per- protocol ( PP ) analysis was performed on those participants who had successfully completed the trial with good compliance rate . Results With respect to primary outcomes , glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis ( p . Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis . These changes were significant between groups at both analyses ( p did not change significantly . Probiotics successfully passed through the gastrointestinal tract . Conclusion Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes", "Certain therapeutic microbes , including Bifidobacteria infantis ( B. infantis ) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions ; however , the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear . In this study , we assessed the impact of oral administration of B. infantis 35624 , for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis ( UC ) ( n = 22 ) , chronic fatigue syndrome ( CFS ) ( n = 48 ) and psoriasis ( n = 26 ) in three separate r and omized , double-blind , placebo-controlled interventions . Additionally , the effect of B. infantis 35624 on immunological biomarkers in healthy subjects ( n = 22 ) was assessed . At baseline , both gastrointestinal ( UC ) and non-gastrointestinal ( CFS and psoriasis ) patients had significantly increased plasma levels of C-reactive protein ( CRP ) and the pro-inflammatory cytokines tumor necrosis factor α ( TNF-α ) and interleukin-6 ( IL-6 ) compared with healthy volunteers . B. infantis 35624 feeding result ed in reduced plasma CRP levels in all three inflammatory disorders compared with placebo . Interestingly , plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS . Furthermore , in healthy subjects , LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells ( P BMC s ) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding . These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions . In conclusion , these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system", "The effect of dietary therapy with a human Lactobacillus strain GG ( ATCC 53103 ) , bovine colostrum , or bovine immune colostrum with specific antibodies against anaerobic intestinal bacteria on gut defence mechanisms were studied in juvenile chronic arthritis . Thirty patients with juvenile chronic arthritis were r and omly allocated to receive a freeze-dried powder of Lactobacillus GG , or bovine colostrum , or bovine immune colostrum , for a two-week period . Immunologic and non-immunologic gut defence mechanisms were indirectly investigated in blood and faecal sample s. In patients receiving Lactobacillus GG , the median ( interquartile range ) frequency of immunoglobulin-secreting cells , determined by enzyme-linked immunospot assay , increased in the IgA class from 1840 ( 690–2530 ) to 3480 ( 1030–13 170)/106 cells ; p=0.02 . Likewise the median ( interquartile range ) frequency of specific antibody-secreting cells against dietary antigens increased during the Lactobacillus GG therapy in the IgM class from 3.8 ( 1.4–5.0 ) to 11.2 (5.0–30.0)/106 cells ; p=0.02 . In addition , Lactobacillus GG therapy decreased the median ( interquartile range ) activity of faecal urease , which has been associated with mucosal tissue damage , from 40.3 ( 21.7–54.3 ) to 28.6 ( 24.5–49.4 ) nmol . min−1 ( mg protein)−1 ; p=0.10 , while , in patients receiving bovine colostrum , faecal urease activity increased ( from 42.2 to 80.6 ; p=0.04 ) . All findings were transient . We suggest that gut defence mechanisms are disturbed in juvenile chronic arthritis and we further suggest that orally administered Lactobacillus GG has a potential to reinforce the mucosal barrier mechanisms in juvenile chronic arthritis", "OBJECTIVES Rheumatoid arthritis ( RA ) is an inflammatory autoimmune disease in which the gut microbiota is altered . Probiotics are microorganisms that can normalize gut microbiota ; thus , they may help to alleviate RA symptoms . The objective of the present clinical trial was to assess the effects of probiotic supplementation on disease activity and inflammatory cytokines in patients with RA . METHODS Forty-six patients with RA were assigned into two groups in this r and omized , double-blind , placebo-controlled clinical trial . The patients in the probiotic group received a daily capsule that contained a minimum of 10(8 ) colony-forming units of Lactobacillus casei 01 for 8 wk . The placebo group took capsules filled with maltodextrin for the same time period . Question naires , anthropometric measurements , and fasting blood sample s were collected , and the participants were assessed by a rheumatologist at baseline and at the end of the trial . RESULTS Disease activity score was significantly decreased by the intervention , and there was a significant difference between the two groups at the end of the study ( P assessed serum proinflammatory cytokines ( tumor necrosis factor-α , interleukin-6 , and interleukin-12 ) significantly decreased in the probiotic group ( P , serum levels of interleukin-1 β were not significantly affected by the probiotic ( P = 0.22 ) . The serum level of regulatory cytokine ( interleukin-10 ) was increased by the supplementation ( P proportion of interleukin-10 to interleukin-12 was significantly increased in the probiotic group as well . CONCLUSIONS L. casei 01 supplementation improved the disease activity and inflammatory status of patients with RA . Further studies are warranted to confirm these results , and such confirmation may lead to the introduction of probiotics as adjunctive therapy for this population", "Background Probiotics might reduce gut-derived microbial lipopolysaccharide ( LPS ) by restoring bowel flora in patients with alcoholic hepatitis ( AH ) . We evaluated the therapeutic effects of probiotics in patients with AH . Patients and methods Between September 2010 and April 2012 , 117 patients ( probiotics 60 and placebo 57 ) were prospect ively r and omized to receive the 7 days of cultured Lactobacillus subtilis/Streptococcus faecium ( 1500 mg/day ) or placebo . All patients were hospitalized and were not permitted to consume alcohol for the 7 days of the study . Liver function test , proinflammatory cytokines , LPS , and colony-forming units by stool culture were examined and compared after therapy . Results In both groups , the mean levels of aspartate aminotransferase/alanine aminotransferase , alkaline phosphatase , & ggr;-glutamyl transpeptidase , bilirubin , and prothrombin time were significantly improved after 7 days of abstinence . In the probiotics group ( baseline and after ) , albumin ( 3.5±0.7 and 3.7±0.6 g/dl , P=0.038 ) and tumor necrosis factor-&agr ; ( 121±244 and 71±123 pg/ml , P=0.047 ) showed differences . In addition , the number of colony-forming units of Escherichia coli was significantly reduced ( 435±287 and 168±210 , P=0.002 ) . In the placebo group , the level of LPS ( 1.7±2.8 and 2.0±2.7 EU/ml ) was significantly increased . In the intergroup comparison , significant differences in the levels of tumor necrosis factor-&agr ; ( P=0.042 ) and LPS ( P=0.028 ) were observed between the groups . Conclusion Immediate abstinence is the most important treatment for patients with AH . In addition , 7 days of oral supplementation with cultured L. subtilis/S. faecium was associated with restoration of bowel flora and improvement of LPS in patients with AH", "To evaluate the effects of probiotic ( VSL#3 ) and omega-3 fatty acid on insulin sensitivity , blood lipids , and inflammation , we conducted a clinical trial in 60 overweight ( BMI > 25 ) , healthy adults , aged 40–60 years . After initial screening the subjects were r and omized into four groups with 15 per group . The four groups received , respectively , placebo , omega-3 fatty acid , probiotic VSL#3 , or both omega-3 and probiotic , for 6 weeks . Blood and fecal sample s were collected at baseline and after 6 weeks . The probiotic ( VSL#3 ) supplemented group had significant reduction in total cholesterol , triglyceride , LDL , and VLDL and had increased HDL ( P VSL#3 improved insulin sensitivity ( P decreased hsCRP , and favorably affected the composition of gut microbiota . Omega-3 had significant effect on insulin sensitivity and hsCRP but had no effect on gut microbiota . Addition of omega-3 fatty acid with VSL#3 had more pronounced effect on HDL , insulin sensitivity and hsCRP . Subjects with low HDL , insulin resistance , and high hsCRP had significantly lower total lactobacilli and bifidobacteria count and higher E. coli and bacteroides count ", "Background . Primary goal of this r and omized , double-blind , placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins . Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress . Methods . Two 2-month treatment periods separated by 2-month washout and crossover , with physical examinations , venous blood testing , and quality of life question naires completed at each visit . Data were analyzed with SAS V9.2 . Results . 22 subjects ( 79 % ) completed the study . Observed trends were as follows ( none reaching statistical significance ): decline in WBC count ( −0.51 × 109/L , P = 0.057 ) and reductions in levels of C-reactive protein ( −8.61 mg/L , P = 0.071 ) and total indoxyl glucuronide ( −0.11 mg% , P = 0.058 ) . No statistically significant changes were observed in other uremic toxin levels or measures of QOL . Conclusions . Renadyl appeared to be safe to administer to ESRD patients on hemodialysis . Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease . Efficacy could not be confirmed definitively , primarily due to small sample size and low statistical power — further studies are warranted", "Objective : Reactive oxygen species ( ROS ) are a major contributing factor in diseases pathophysiology in critically ill patients . Oxidative stress usually occurs in critical illnesses , specifically during sepsis , and organ dysfunction . The anti-oxidative properties of probiotics may serve as a defense in intestine and overcome various oxidative stresses . The aim of this trial was to determine the effect of probiotics on inflammation , antioxidant capacity and lipid peroxidation in critically ill patients . Methodology : Forty patients admitted to the intensive care unit were enrolled in this double-blind , r and omized controlled trial . They were r and omized to receive placebo or probiotic for 7 days . Serum levels of Total Antioxidant Capacity ( TAC ) , Malodialdehyde ( MDA ) , C-Reactive Protein ( CRP ) and Acute Physiology and Chronic Health Evaluation ( APACHE II ) score were measured before initiation of the study and on the 7th day . Results : There was a significant difference in CRP levels and APACHE II score between two groups at the end of the study ( P= 0.003 and 0.001 , respectively ) . There was not a significant difference in levels of TAC and MDA between two groups . Conclusions : Administration of probiotics to critically ill patients caused reduction in inflammation and improvement of clinical outcome . However , there were not significant changes in markers of oxidative stress", "Summary Background To examine the effect of probiotics as adjunctive therapy for the treatment of rheumatoid arthritis ( RA ) . A sample size of 30 subjects was calculated to determine a moderate effect . Material / Methods A three month double-blind , placebo-controlled study was performed using probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 capsules administered orally . Inclusion criteria required at least 4 swollen and 4 tender joints and stable medications with no steroids for at least 1 month prior to and during the study . Twenty-nine patients with RA were r and omized to treatment . ACR20 responses , serum cytokine levels and safety parameters were assessed . Results Fifteen patients were r and omized to the probiotic group , and 14 to placebo . Three subjects in the probiotic ( 20 % ) and one in the placebo group ( 7 % ) achieved an ACR20 response ( p= 0.33 ) . There was no statistically significant difference between individual components of the ACR20 criteria . Changes in cytokines favored placebo over probiotic . There was a significant improvement in the Health Assessment Question naire ( HAQ ) score in the probiotic group from visit 1 to visit 3 ( p=0.02 ) but no between-group differences . Conclusions Due to inclusion criteria , patients selected for the study had stable RA with chronic synovitis , and thus it may have been difficult for an adjunctive therapy to demonstrate improvement within 3 months . Although probiotics did not clinical ly improve RA as measured by the ACR20 , it is interesting that there was functional improvement seen within the probiotic group compared to placebo", "Background / Objectives : The percentage of hypercholesterolemic individuals not reaching their LDL-cholesterol ( LDL-C ) goal remains high and additional therapeutic strategies should be evaluated . The objective of this study was to evaluate the cholesterol-lowering efficacy and mechanism of action of bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 capsules in hypercholesterolemic adults . Subjects/ Methods : A total of 127 subjects completed a r and omized , double-blind , placebo-controlled , parallel-arm , multicenter study . Subjects were r and omized to consume L. reuteri NCIMB 30242 capsules or placebo capsules over a 9-week intervention period . The primary outcome was LDL-C relative to placebo at the study end point . Results : L. reuteri NCIMB 30242 capsules reduced LDL-C by 11.64 % ( P total cholesterol by 9.14 % , ( P non-HDL-cholesterol ( non-HDL-C ) by 11.30 % ( P apoB-100 by 8.41 % ( P=0.002 ) relative to placebo . The ratios of LDL-C/HDL-cholesterol ( HDL-C ) and apoB-100/apoA-1 were reduced by 13.39 % ( P=0.006 ) and 9.00 % ( P=0.026 ) , respectively , relative to placebo . Triglycerides and HDL-C were unchanged . High-sensitivity C-reactive protein and fibrinogen were reduced by 1.05 mg/l ( P=0.005 ) and 14.25 % ( P=0.004 ) relative to placebo , respectively . Mean plasma deconjugated bile acids were increased by 1.00 nmol/l ( P=0.025 ) relative to placebo , whereas plasma campesterol , sitosterol and stigmasterol were decreased by 41.5 % , 34.2 % and 40.7 % , respectively . Conclusions : The present results suggest that the deconjugation of intraluminal bile acids results in reduced absorption of non-cholesterol sterols and indicate that L. reuteri NCIMB 30242 capsules may be useful as an adjunctive therapy for treating hypercholesterolemia", "OBJECTIVE To investigate whether a probiotic mix has additional effects when compared with an isolated dietary intervention on the body composition , lipid profile , endotoxemia , inflammation , and antioxidant profile . METHODS Women who had excess weight or obesity were recruited to a r and omized , double-blind trial and received a probiotic mix ( Lactobacillus acidophilus and casei ; Lactococcus lactis ; Bifidobacterium bifidum and lactis ; 2 × 1010 colony-forming units/day ) ( n = 21 ) or placebo ( n = 22 ) for 8 weeks . Both groups received a dietary prescription . Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry . The lipid profile , lipid accumulation product , plasma fatty acids , lipopolysaccharide , interleukin-6 , interleukin-10 , tumor necrosis factor-α , adiponectin , and the antioxidant enzymes activities were analyzed . RESULTS In comparison with the dietary intervention group , the dietary intervention + probiotic mix group showed a greater reduction in the waist circumference ( -3.40 % vs. -5.48 % , P = 0.03 ) , waist-height ratio ( -3.27 % vs. -5.00 % , P = 0.02 ) , conicity index ( -2.43 % vs. -4.09 % P = 0.03 ) , and plasma polyunsaturated fatty acids ( 5.65 % vs. -18.63 % , P = 0.04 ) and an increase in the activity of glutathione peroxidase ( -16.67 % vs. 15.62 % , P of a probiotic mix reduced abdominal adiposity and increased antioxidant enzyme activity in a more effective way than an isolated dietary intervention", "We conducted two r and omized , placebo-controlled , double-blind studies of Lactobacillus plantarum No. 14 ( LP14 ) in female students with seasonal allergic diseases . We also examined the mitogenic activity and cytokine inducibility of LP14 using Peyer ’s patch cells and mesenteric lymph node cells of swine . For subjects who took 8.7 × 108 of LP14 , a significant improvement in ocular symptom-medication score was observed . In the placebo group , the T helper type 1 (Th1)/T helper type 2 ( Th2 ) ratio tended to decrease after a 6-week intake period , while in the LP14 group , the percentage of Th1 cells significantly increased . Post-intake eosinophil counts significantly increased in comparison to those at intake cessation in the placebo group , but it appeared to be suppressed in the LP14 group . There were no changes in fecal microflora . LP14 strongly induced the gene expression of Th1-type cytokines . This study indicates the clinical effects of LP14 on seasonal allergic diseases", "BACKGROUND AND OBJECTIVES Probiotics create a biofilm and protect the oral tissues against the action of periodontal pathogenic bacteria . The aim of this study was to evaluate the effects of the oral probiotic Lactobacillus reuteri Prodentis upon the peri-implant health of edentulous patients with dental implants and peri-implant mucositis , establishing comparisons vs implants without peri-implant disease . MATERIAL AND METHODS A double-blind , placebo-controlled , prospect i ve cross-over study was made . The patients were all edentulous and were divided into two groups , ( A ) no peri-implant disease , and ( B ) peri-implant mucositis affecting one or more implants . Patients with peri-implantitis were excluded . The dosage was one tablet every 24 h over 30 d. All patients in both groups initially received the oral probiotic Lactobacillus reuteri Prodentis , followed by placebo . Patients started with probiotic treatment during 30 d , followed by a 6 mo washout period and the administration of placebo for the same period . The following parameters were studied : crevicular fluid volume , modified plaque index , probing depth , modified gingival index , and concentrations of interleukin 1β , interleukin 6 and interleukin 8 . RESULTS A total of 77 implants were evaluated in 34 patients . Group A involved 22 patients with 54 implants without peri-implant alterations , and group B , 12 patients with mucositis affecting one or more implants ( 23 implants ) . After treatment with the probiotic , both the patients with mucositis and the patients without peri-implant disease showed improvements in the clinical parameters , with reductions in cytokine levels . In contrast , no such changes were observed with placebo . CONCLUSIONS After treatment with the probiotic Lactobacillus reuteri in patients with implants presenting mucositis , the clinical parameters improved , and the cytokine levels decreased - in contraposition to the observations in the placebo group . Probiotic administration may be regarded as a good alternative for both the treatment of peri-implant mucositis and its prevention , as it also improved clinical parameters in the healthy individuals . Further studies involving larger patient series are needed regarding the effects of probiotics upon peri-implant health", "Objective . To investigate the effect of an orally administered probiotic on disease activity , fatigue , quality of life , and intestinal symptoms in patients with active spondyloarthritis . Methods . Patients with active spondyloarthritis [ defined as Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) ≥ 3 , Bath Ankylosing Spondylitis Functional Index ( BASFI ) ≥ 3 , Maastricht Ankylosing Spondylitis Enthesitis Score ( MASES ) ≥ 2 , or peripheral joint count ≥ 2 ] were r and omized to oral probiotic or placebo for 12 weeks . Patients and assessors were blinded to treatment allocation . The primary outcome measure was 10 % improvement in the BASFI . Additional outcome measures were improvements in the ASsessment s in Ankylosing Spondylitis (ASAS)-endorsed core domains : pain , spinal mobility , patient global , peripheral joint and entheseal scores , stiffness , C-reactive protein , and fatigue . The ASAS20 criteria , a composite measure of response , were also applied . Quality of life and bowel symptoms were quantified using the Ankylosing Spondylitis Quality of Life Question naire ( ASQoL ) and Dudley Inflammatory Bowel Symptom Question naire ( DISQ ) . Results . Sixty-three patients were r and omized to oral probiotic ( n = 32 ) or placebo ( n = 31 ) . All patients completed the trial . No significant difference was noted between groups in any of the core domains . The mean BASFI fell from 3.5 ± 2.0 to 2.9 ± 1.9 in the probiotic group and from 3.6 ± 1.9 to 3.1 ± 2.2 in the placebo group ( p = 0.839 ) . The mean BASDAI fell from 4.2 ± 2.2 to 3.2 ± 2.1 in the probiotic group and 4.5 ± 2.0 to 3.9 ± 2.2 in the placebo group ( p = 0.182 ) . No significant adverse events were recorded in the probiotic-treated group . Conclusion . In this r and omized controlled trial , the probiotic combination administered did not demonstrate significant benefit over placebo , despite a theoretical rationale for this therapy", "Objective : To study the effects of Lactobacillus rhamnosus GG ( LGG ) on rheumatoid arthritis ( RA ) . Methods : Twenty‐one RA patients were r and omised to receive 2 capsules of LGG or a placebo twice daily in double‐blind fashion for 12 months . Arthritis activity was evaluated by clinical examination , HAQ index , and laboratory tests ( e.g. ESR , CRP , pro‐ and anti‐inflammatory cytokines ) . Results : There were no statistical differences in the clinical parameters , biochemical variables and HAQ index between the study groups over the intervention period . The mean number of tender and swollen joints decreased from 8.3 to 4.6 in the Lactobacillus group and from 5.5 to 4.8 in the placebo group ( p=0.41 ) . According to the global assessment the RA activity was reduced in 71 % ( LGG group ) vs. 30 % ( controls ) ( p=0.15 ) . Serum IL‐1β increased slightly in the LGG group ( p=0.07 ) , but no differences were seen in IL‐6 , TNF‐α , MPO , IL‐10 or 1L‐12 . Conclusions : Although there were no statistical significant differences in the activity of RA , more subjects in the LGG group reported subjective well being . More studies on the effects of probiotic bacteria in RA are needed", "Probiotic microorganisms have been shown to be effective in the treatment of allergic inflammation and food allergy , but their efficacy remains controversial . This study tested the effect of a yogurt supplemented with a probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis ( JCPsis ) . Forty subjects with a clinical history of JCPsis were given yoghurt either containing BB536 ( BB536 yoghurt ) or without BB536 ( placebo yoghurt ) at 2 X 100 g per day for 14 weeks , in a r and omized , double-blind , placebo-controlled trial . Subjective symptoms and self-care measures were recorded daily and blood sample s were taken before and during the intervention ( at weeks 4 , 9 , and 14 ) to measure the blood parameter levels related to JCPsis . Yoghurt supplemented with BB536 significantly alleviated eye symptoms compared with placebo yoghurt ( odds ratio 0.31 ; 95 % confidence interval 0.10 - 0.97 ; p = 0.044 ) . Although no statistically significant differences were detected , nasal symptoms such as itching , rhinorrhea , and blockage , as well as throat symptoms tended to be relieved with the BB536 yoghurt . BB536 tended to suppress the decreasing blood levels of interferon-gamma ( IFN-y ) and the increasing blood eosinophil rates ; a significantly higher IFN-gamma level was observed for the difference from baseline at week 4 . A decreased trend in the difference from baseline levels of JCP-specific IgE levels was also observed at week 4 in the BB536 group compared with the placebo group . In conclusion , these results suggest that intake of BB536-supplemented yoghurt may relieve JCPsis symptoms , probably through a modulating effect on Th balance", "Background : Polycystic ovary syndrome ( PCOS ) is a polygenic endocrine disorder in women of reproductive age that lead to infertility . The aim of this study was to investigate the effects of probiotic on pancreatic β-cell function and C-reactive protein ( CRP ) in PCOS patients . Methods : This r and omized double-blind placebo-controlled clinical trial was conducted among 72 women aged 15–40 years old diagnosed with PCOS . Participants were r and omly assigned to two groups receiving : ( 1 ) Probiotic supplements ( n = 36 ) , ( 2 ) placebo ( n = 36 ) for 8-week . Fasting blood sample s were taken at baseline and after 8-week of intervention . Results : Probiotic supplementation , compare with placebo , reduced fasting blood sugar ( −4.15 ± 2.87 vs. 2.57 ± 5.66 mg/dL , respectively P = 0.7 ) , serum insulin levels in crude model ( −0.49 ± 0.67 vs. 0.34 ± 0.82 μIU/mL , respectively , P = 0.09 ) , homeostasis model of assessment -insulin resistance score ( −0.25 ± 0.18 vs. −0.05 ± 0.18 , respectively , P = 0.14 ) nonsignificantly . Serum insulin levels after adjustment with covariates reduced significantly in probiotic group ( P = 0.02 ) . We did not found any significant differences in mean changes of CRP between groups ( −0.25 ± 0.18 vs. −0.05 ± 0.18 , respectively , P = 0.14 ) . Conclusions : A 8-week multispecies probiotics supplementation had nonsignificantly beneficial effect on pancreatic β-cell function and CRP in PCOS patients . After adjustment for some covariates , serum insulin changes were significantly different between groups", "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", "Background : Chronic inflammation is one of the causes of anemia in chronic renal failure patients under hemodialysis . Probiotics probably establish a balance between pro- and anti-inflammatory cytokines . The study was conducted to determine the effects of probiotic supplementation on hemoglobin ( Hb ) in hemodialysis patients . Material s and Methods : A parallel clinical trial was conducted in which patients were r and omly allocated into two groups . The intervention group ( n = 18 ) was given a 500 mg probiotic supplement ( a capsule ) every day whereas the control group ( n = 18 ) received placebo ( a capsule ) , both for 3 months . Hb levels and C-reactive protein ( CRP ) levels were measured for three periods . The data were analyzed in SPSS-16 using statistical tests including the t-test and repeated- measures ANOVA . Results : In the probiotic supplementation group , the mean Hb was 9.22 ± 1.04 mg/dl before the intervention and reached 10.85 ± 1.177 mg/dl afterward , while in the placebo group , the mean Hb level was 9.38 ± 0.97 mg/dl before the intervention and reached 10.03 ± 1.97 mg/dl afterward ( P > 0.05 ) . During the study , the placebo caused to increase of Hb temporary , but in longer term , the effect of probiotic was more manifested . Hb levels increased in both groups although the change was not statistically significant ( P > 0.05 ) . The findings showed no significant differences between the two groups in either the pre- or post-intervention CRP levels ( P = 0.239 ) . Conclusion : Probiotic supplementation decreased Hb fluctuations in hemodialysis patients but did not result in a significant increase in Hb levels . Similar studies are therefore recommended to be conducted with a prolonged duration of the study or an increased probiotic dose with larger sample size to complete the results of the present study", "Dysbalance in gut microbiota has been linked to increased microbial translocation , leading to chronic inflammation in HIV- patients , even under effective HAART . Moreover , microbial translocation is associated with insufficient reconstitution of CD4+T cells , and contributes to the pathogenesis of immunologic non-response . In a double-blind , r and omised , placebo-controlled trial , we recently showed that , compared to placebo , 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation ( Lipopolysaccharide-binding protein or LBP ) and systemic inflammation ( IL-6 ) in 44 HIV virologically suppressed patients , half of whom ( n = 22 ) had immunologic non-response to antiretroviral therapy ( . The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition , with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation . In this study , we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome ( faecal sample s ) in these 44 patients r and omized to receive oral supplementation with probiotic or placebo for 12 weeks . Compared to the placebo group , in individuals treated with probiotic we observed lower concentrations of some gut species , such as those of the Clostridiaceae family , which were correlated with systemic levels of bacterial translocation and inflammation markers . In a sub- study of these patients , we observed significantly higher parameters of microbial translocation ( LBP , soluble CD14 ) and systemic inflammation in immunologic non-responders than in immunologic responders , which was correlated with a relative abundance of specific gut bacterial groups ( Lachnospiraceae genus and Proteobacteria ) . Thus , in this work , we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition . Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target", "Goals To study the role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis ( AP ) . Background Bacterial translocation has been implicated in infective complications in AP , which has been shown to be prevented by probiotics . Study A double-blind , r and omized placebo-controlled trial was conducted . Consecutive patients with AP presenting within 72 hours after the onset of abdominal pain or who had been nil orally at the time of presentation for up to 5 days were included in the study . The probiotic group received 4 sachets of Probiotics ( 2.5 billion bacteria per sachet ) whereas the placebo group received 4 sachets of placebo for 7 days . Primary outcome measures were effect on gut permeability [ assessed by lactulose/mannitol ( L/M ) excretion in urine ] and endotoxemia assessed by endotoxin-core antibody types IgG and IgM ( EndoCab IgG and IgM ) . Secondary outcome measures were mortality , total hospital/intensive care unit stay , abdominal discomfort , organ failure , C-reactive protein , and prealbumin levels . The study was prematurely stopped after the publication of probiotic prophylaxis in patients with predicted severe acute pancreatitis trial . Results From March 2007 to May 2008 , 50 patients with AP were included in the study ( 26 in placebo group and 24 in probiotic group ) . There was no difference after intervention in gut permeability , whereas values of C-reactive protein and immunoglobulins decreased significantly [ IgG : 140 ( 20–920 ) to 90 ( 20–600 ) GGU/mL and IgM : 65 ( 13–230 ) to 51 ( 9–240 ) GMU/mL ] in the probiotic group . No difference was observed in prealbumin values , duration of hospital/intensive care unit stay , and mortality in both the groups . Conclusions No significant trend was identified for an effect of probiotics on gut permeability or endotoxemia in AP . However , the study was underpowered owing to premature study termination", "ABSTRACT Objective : The development of alternative approaches to prevent and /or treat osteoporosis , as a chronic progressive bone disease , is being considered currently . Among dietary supplements , probiotics may have favorable effects on bone metabolism . Therefore , the aim of this study was to evaluate the effects of a multispecies probiotic supplementation on bone biomarkers and bone density in osteopenic postmenopausal women . Methods : This r and omized double-blind placebo-controlled clinical trial was performed on 50 patients with osteopenia aged 50–72 years . Participants were r and omly assigned to take either a multispecies probiotic supplement ( GeriLact ; n = 25 ) or placebo ( n = 25 ) for 6 months . GeriLact contains 7 probiotic bacteria species . Participants received 500 mg Ca plus 200 IU vitamin D daily . Bone mineral density ( BMD ) of lumbar spine and total hip and blood biomarkers including bone-specific alkaline phosphatase ( BALP ) , osteocalcin ( OC ) , collagen type 1 cross-linked C-telopeptide ( CTX ) , deoxypyridinoline ( DPD ) , parathyroid hormone ( PTH ) , 25-OH vitamin D , and serum pro-inflammatory cytokines ( tumor necrosis factor [TNF]-α and interleukin [IL]-1β ) were assessed at baseline and at the end of the study . Results : The multispecies probiotic significantly decreased BALP ( p = 0.03 ) and CTX ( p = 0.04 ) levels in comparison with the control group but had no effect on BMD of the spine and total hip . Moreover , there was a statistically significant decrease in serum PTH ( p = 0.01 ) and TNF-α ( p = 0.02 ) in the intervention group compared to the placebo group . Conclusions : These results may suggest the favorable effects of the multispecies probiotic supplementation for 6 months on bone health in postmenopausal women due to slowing down the rate of bone turnover ", "Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha ( TNF-α ) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality . Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease . The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis ( PD ) patients . The decline of residual renal function , peritonitis episodes , and cardiovascular events were also recorded . From July 2011 to June 2012 , a r and omised , double-blind , placebo-controlled trial was conducted in PD patients . The intervention group received one capsule of probiotics containing 10(9 ) cfu Bifobacterium bifidum A218 , 10(9 ) cfu Bifidobacterium catenulatum A302 , 10(9 ) cfu Bifidobacterium longum A101 , and 10(9 ) cfu Lactobacillus plantarum A87 daily for six months , while the placebo group received similar capsules containing maltodextrin for the same duration . Levels of serum TNF-α , interferon gamma , IL-5 , IL-6 , IL-10 , IL-17 , and endotoxin were measured before and six months after intervention . 39 patients completed the study ( 21 in the probiotics group and 18 in the placebo group ) . In patients receiving probiotics , levels of serum TNF-α , IL-5 , IL-6 , and endotoxin significantly decreased after six months of treatment , while levels of serum IL-10 significantly increased . In contrast , there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months . In addition , the residual renal function was preserved in patients receiving probiotics . In conclusion , probiotics could significantly reduce the serum levels of endotoxin , pro-inflammatory cytokines ( TNF-α and IL-6 ) , IL-5 , increase the serum levels of anti-inflammatory cytokine ( IL-10 ) , and preserve residual renal function in PD patients", "OBJECTIVE The objective of the study was to evaluate the effects of probiotic supplementation on the gut microbiota profile and inflammatory markers in chronic kidney disease patients undergoing maintenance hemodialysis ( HD ) . DESIGN AND METHODS This was a r and omized , double-blind , placebo-controlled study . Forty-six HD patients were assigned to receive 1 of 2 treatments : probiotic ( n = 23 ; Streptococcus thermophilus , Lactobacillus acidophilus e Bifidobacterialongum , 90 billion colony-forming units per day ) or placebo ( n = 23 ) daily for 3 months . Blood and feces were collected at baseline and after intervention . The inflammatory markers ( C-reactive protein and interleukin-6 ) were analyzed by immunoenzymatic assay ( enzyme-linked immunosorbent assay ) . Uremic toxins plasma levels ( indoxyl sulfate , p-cresyl sulfate , and indole-3-acetic acid ) were obtained by Reversed-Phase High-Performance Liquid Chromatography . Routine laboratory parameters were measured by st and ard techniques . Fecal pH was measured by the colorimetric method , and the gut microbiota profile was assessed by Denaturing Gradient Gel Electrophoresis analysis . RESULTS Sixteen patients remained in the probiotic group ( 11 men , 53.6 ± 11.0 year old , 25.3 ± 4.6 kg/m2 ) and 17 in the placebo group ( 10 men , 50.3 ± 8.5 year old , 25.2 ± 5.7 kg/m2 ) . After probiotic supplementation there was a significant increase in serum urea ( from 149.6 ± 34.2 mg/dL to 172.6 ± 45.0 mg/dL , P = .02 ) , potassium ( from 4.4 ± 0.4 mmol/L to 4.8 ± 0.4 mmol/L , P = .02 ) , and indoxyl sulfate ( from 31.2 ± 15.9 to 36.5 ± 15.0 mg/dL , P = .02 ) . The fecal pH was reduced from 7.2 ± 0.8 to 6.5 ± 0.5 ( P = .01 ) . These parameters did not change significantly in placebo group . Changes in the percentage delta ( Δ ) between groups were exhibited with no statistical differences observed . The inflammatory markers and gut profile were not altered by supplementation . CONCLUSIONS Aprobiotic supplementation failed to reduce uremic toxins and inflammatory markers . Therefore , probiotic therapy should be chosen with caution in HD patients . Further studies addressing probiotic therapy in chronic kidney disease patients are needed", "Background Although the effects of probiotics on the immune system have been extensively evaluated under disease states , their role in healthy situations remains unclear , since changes are hardly expected under immunological homeostasis . EFSA indicates that vaccination protocol s could be used to evaluate the potential role of probiotics to improve the immune response against antigen challenges . The aim of the study was to evaluate the effect of Lactobacillus coryniformis CECT5711 ( Lc ) on the specific immunity of healthy volunteers undergoing vaccination with Hepatitis A virus ( HAV ) . Methods One hundred twenty-three healthy adults were r and omised into three groups to follow a 6-week ( wk ) intervention and all received an intramuscular HAV vaccine 2 weeks after starting the intervention : 1 ) PRO1 received Lc for 2weeks ( 1 capsule/day ; 3 × 109 CFU/capsule ) and placebo capsules after vaccination ; 2 ) PRO2 received a daily capsule of Lc ( 3 × 109 cfu/day ) before and after the challenge ; 3 ) Control group ( C ) received a daily placebo capsule before and after the vaccine . Blood sample s were collected at the beginning ( visit 1 ; V1 ) and after 2 ( V2 ) and 6 weeks ( V3 ) of the intervention . At each visit , lymphocyte subset counts and cytokine levels were analysed . Specific HAV antibodies were analysed at V1 and V3 . To evaluate differences between groups , one-way ANOVA with Bonferroni post-hoc test were used regarding lymphocyte subset counts and specific HAV antibodies production , and Friedman test of related sample s and Kendall concordance coefficient for cytokines production . Chi square test was used to analyse seroconversion rates . Results Specific HAV antibodies were significantly higher in PRO1 ( 50.54 ± 29.57 ) compared to C ( 36.23 ± 16.45 ) ( P = 0.017 ) and showed an intermediate value in PRO2 ( 41.61 ± 15.74 ) . Seroconversion rates were similar in the three groups ( 97.3 , 92.3 and 97.4 % in C , PRO1 and PRO2 respectively ) . Memory T-helper lymphocytes increased in V3 vs. V1 ( P = 0.032 ) in PRO2 . No differences were found in cytokine concentrations . Conclusion Mixed results have been found regarding the usefulness of Lc supplementation to increase the antigen-specific antibody response to an immune challenge . Clinical trial registration number : EudraCT Number 2016 - 000183 - 42 . Registered 19 January 2016 . Retrospectively registered", "There is an increasing interest in the intestinal and immunological effects of probiotics . The aim of the present study is to evaluate the tolerance and beneficial effects in healthy adults of the strain , Lactobacillus salivarius CECT5713 isolated from breast milk . A phase II , r and omized , double-blinded , placebo-controlled human clinical trial was carried out in 40 healthy adults . The Probiotic group received a daily dose of 2 x 10(8 ) CFU of L. salivarius CECT5713 in capsules during 4 weeks while volunteers of the control received only a placebo . Gastrointestinal and immunological parameters were analyzed . Results showed that L. salivarius CECT5713 was well tolerated and no adverse effects were detected . Consumption of the probiotic strain increased fecal lactobacilli counts ( 7.9+/-0.1 vs. 7.05+/-0.2 CFU/g feces , P=0.001 ) . Also , an improvement in the frequency of defecation ( P=0.04 ) was observed . Probiotic treatment induced significantly the percentage of NK cells and monocytes , as well as the plasmatic levels of immunoglobulins M , A and G , and the regulatory cytokine IL-10 ( 72.3+/-11.7 in probiotic group vs. 27.3+/-6.4 pg/mL in control group , P L. salivarius CECT5713 to healthy adults is safe and improve gut microbiota and different parameters related to immune response", "BACKGROUND Probiotics , by altering gut flora , may favourably alter portal haemodynamics in patients with cirrhosis . AIM To investigate the effect of probiotics on portal pressure in patients with cirrhosis . METHODS R and omized double-blind placebo-controlled trial conducted in G.B. Pant Hospital , New Delhi . A total of 94 cirrhotic patients having large oesophageal varices without history of variceal bleeding were r and omized to three treatment groups and given 2 months ' treatment with propranolol plus placebo , propranolol plus antibiotics ( norfloxacin 400 mg BD ) or propranolol plus probiotic ( VSL#3 , 900 billion/day ) r and omly assigned in 1:1:1 ratio . Outcome measures were change in Hepatic venous pressure gradient ( HVPG ) : Response rate ( Percentage of patients having a decrease from baseline of ≥20 % or to ≤12 mm Hg ) and changes from baseline ; biochemical markers of inflammation : changes from baseline . RESULTS Adjunctive probiotics increased the response rate compared with propranolol alone ( 58 % vs. 31 % , P = 0.046 ) , similar to adjunctive antibiotics ( 54 % ) . The mean fall in HVPG was greater with either adjunctive probiotics ( 3.7 mm Hg vs. 2.1 mm Hg , P = 0.061 ) or adjunctive antibiotics ( 3.4 mm Hg ) than with propranolol alone . Both adjunctive therapies were associated with greater decreases in TNF-α levels ( in both peripheral and hepatic venous blood ) that result ed from propranolol-only treatment . No clinical ly relevant between-group differences were observed in the type or frequency of adverse events . CONCLUSIONS Adjunctive probiotic ( VSL#3 ) improved the response rate to propranolol therapy and was safe and well tolerated in patients with cirrhosis . Adjunctive probiotic therapy merits further study for reduction in portal pressure", "Abstract Objective : This study investigated the efficacy and safety of supplementation with probiotics in improving chronic pulmonary symptoms due to sulfur mustard ( SM ) exposure . Methods : In a r and omized double-blind placebo-controlled study , 65 subjects suffering from chronic pulmonary complications of SM were assigned to one probiotic capsule ( 1 × 109 CFU containing seven strains of lactic acid-producing bacteria ) every 12 h or an identical placebo for six weeks . Serum high-sensitivity C-reactive protein ( CRP ) concentrations , pulmonary function tests ( FEV1 , FEV1/FVC and MMEF 25–75 % ) and COPD assessment test ( CAT ) were assessed at baseline and at the end of trial . Results : The groups were comparable in baseline characteristics . There were significant improvements in FEV1/FVC in the probiotic but not in placebo group . CAT scores were decreased in both study groups . However , between-group comparison of changes in the assessed parameters reached statistical significance only for CAT score ( p of adverse events during the course of trial . Conclusions : Findings of the present trial favor the efficacy of probiotic supplementation in improving the pulmonary symptoms of SM-exposed subjects" ]

[ "Type 2 diabetes ( T2D ) is associated with increased risk of morbidity and premature mortality . Among those at high risk , incidence can be halved through healthy changes in behaviour . Information about genetic and phenotypic risk of T2D is now widely available . Whether such information motivates behaviour change is unknown . We aim to assess the effects of communicating genetic and phenotypic risk of T2D on risk-reducing health behaviours , anxiety , and other cognitive and emotional theory-based antecedents of behaviour change . In a parallel group , open r and omised controlled trial , approximately 580 adults born between 1950 and 1975 will be recruited from the on-going population -based , observational Fenl and Study ( Cambridgeshire , UK ) . Eligible participants will have undergone clinical , anthropometric , and psychosocial measurements , been genotyped for 23 single-nucleotide polymorphisms associated with T2D , and worn a combined heart rate monitor and accelerometer ( Actiheart ® ) continuously for six days and nights to assess physical activity . Participants are r and omised to receive either st and ard lifestyle advice alone ( control group ) , or in combination with a genetic or a phenotypic risk estimate for T2D ( intervention groups ) . The primary outcome is objective ly measured physical activity . Secondary outcomes include self-reported diet , self-reported weight , intention to be physically active and to engage in a healthy diet , anxiety , diabetes-related worry , self-rated health , and other cognitive and emotional outcomes . Follow-up occurs eight weeks post-intervention . Values at follow-up , adjusted for baseline , will be compared between r and omised groups . This study will provide much needed evidence on the effects of providing information about the genetic and phenotypic risk of T2D . Importantly , it will be among the first to examine the impact of genetic risk information using a r and omised controlled trial design , a population -based sample , and an objective ly measured behavioural outcome . Results of this trial , along with recent evidence syntheses of similar studies , should inform policy concerning the availability and use of genetic risk information . Current Controlled Trials IS RCT", "Background There are few empirical data to inform the debate surrounding the use and regulation of direct-to-consumer ( DTC ) genome-wide disease risk tests . This study aim ed to determine the long term psychological , behavioural , and clinical impacts of genomic risk testing for common disease . Methods The Scripps Genomic Health Initiative is a prospect i ve longitudinal cohort study of adults who purchased the Navigenics Health Compass , a commercially available genomic test . Web based assessment s were administered at baseline , short ( 3 months ) , and long term ( 1 year ) follow-up . Results 2240 participants completed either or both follow-ups and a subset of 1325 completed long term follow-up . There were no significant differences from baseline in anxiety ( p=0.50 ) , fat intake ( p=0.34 ) , or exercise ( p=0.39 ) at long term follow-up , and 96.8 % of the sample had no test related distress . Longitudinal linear mixed model analyses were consistent with results of cross-sectional analyses . Screening test completion was associated with sharing genomic test results with a physician ( 36.0 % shared ; p perceived utility of the test ( 61.5 % high perceived utility ; p=0.002 ) , but was not associated with the genomic risk estimate values themselves . Conclusions Over a third of DTC genomic test recipients shared their results with their own physician during an approximate 1 year follow-up period , and this sharing was associated with higher screening test completion . Genomic testing was not associated with long term psychological risks , and most participants reportedly perceived the test to be of high personal utility", "Objectives To assess the performance of a panel of common single nucleotide polymorphisms ( genotypes ) associated with type 2 diabetes in distinguishing incident cases of future type 2 diabetes ( discrimination ) , and to examine the effect of adding genetic information to previously vali date d non-genetic ( phenotype based ) models developed to estimate the absolute risk of type 2 diabetes . Design Workplace based prospect i ve cohort study with three 5 yearly medical screenings . Participants 5535 initially healthy people ( mean age 49 years ; 33 % women ) , of whom 302 developed new onset type 2 diabetes over 10 years . Outcome measures Non-genetic variables included in two established risk models — the Cambridge type 2 diabetes risk score ( age , sex , drug treatment , family history of type 2 diabetes , body mass index , smoking status ) and the Framingham offspring study type 2 diabetes risk score ( age , sex , parental history of type 2 diabetes , body mass index , high density lipoprotein cholesterol , triglycerides , fasting glucose)— and 20 single nucleotide polymorphisms associated with susceptibility to type 2 diabetes . Cases of incident type 2 diabetes were defined on the basis of a st and ard oral glucose tolerance test , self report of a doctor ’s diagnosis , or the use of anti-diabetic drugs . Results A genetic score based on the number of risk alleles carried ( range 0 - 40 ; area under receiver operating characteristics curve 0.54 , 95 % confidence interval 0.50 to 0.58 ) and a genetic risk function in which carriage of risk alleles was weighted according to the summary odds ratios of their effect from meta-analyses of genetic studies ( area under receiver operating characteristics curve 0.55 , 0.51 to 0.59 ) did not effectively discriminate cases of diabetes . The Cambridge risk score ( area under curve 0.72 , 0.69 to 0.76 ) and the Framingham offspring risk score ( area under curve 0.78 , 0.75 to 0.82 ) led to better discrimination of cases than did genotype based tests . Adding genetic information to phenotype based risk models did not improve discrimination and provided only a small improvement in model calibration and a modest net reclassification improvement of about 5 % when added to the Cambridge risk score but not when added to the Framingham offspring risk score . Conclusion The phenotype based risk models provided greater discrimination for type 2 diabetes than did models based on 20 common independently inherited diabetes risk alleles . The addition of genotypes to phenotype based risk models produced only minimal improvement in accuracy of risk estimation assessed by recalibration and , at best , a minor net reclassification improvement . The major translational application of the currently known common , small effect genetic variants influencing susceptibility to type 2 diabetes is likely to come from the insight they provide on causes of disease and potential therapeutic targets", "Background Obesity rates in the United States have escalated in recent decades and present a major challenge in public health prevention efforts . Currently , testing to identify genetic risk for obesity is readily available through several direct-to-consumer companies . Despite the availability of this type of testing , there is a paucity of evidence as to whether providing people with personal genetic information on obesity risk will facilitate or impede desired behavioral responses . Purpose We describe the key issues in the design and implementation of a r and omized controlled trial examining the clinical utility of providing genetic risk information for obesity . Methods Participants are being recruited from the Coriell Personalized Medicine Collaborative , an ongoing , longitudinal research cohort study design ed to determine the utility of personal genome information in health management and clinical decision making . The primary focus of the ancillary Obesity Risk Communication Study is to determine whether genetic risk information added value to traditional communication efforts for obesity , which are based on lifestyle risk factors . The trial employs a 2 × 2 factorial design in order to examine the effects of providing genetic risk information for obesity , alone or in combination with lifestyle risk information , on participants ’ psychological responses , behavioral intentions , health behaviors , and weight . Results The factorial design generated four experimental arms based on communication of estimated risk to participants : ( 1 ) no risk feedback ( control ) , ( 2 ) genetic risk only , ( 3 ) lifestyle risk only , and ( 4 ) both genetic and lifestyle risk ( combined ) . Key issues in study design pertained to the selection of algorithms to estimate lifestyle risk and determination of information to be provided to participants assigned to each experimental arm to achieve a balance between clinical st and ards and method ological rigor . Following the launch of the trial in September 2011 , implementation challenges pertaining to low enrollment and differential attrition became apparent and required immediate attention and modifications to the study protocol . Although monitoring of these efforts is ongoing , initial observations show a doubling of enrollment and reduced attrition . Limitations The trial is evaluating the short-term impact of providing obesity risk information as participants are followed for only 3 months . This study is built upon the structure of an existing personalized medicine study wherein participants have been provided with genetic information for other diseases . This nesting in a larger study may attenuate the effects of obesity risk information and has implication s for the generalizability of study findings . Conclusions This r and omized trial examines value of obesity genetic information , both when provided independently and when combined with lifestyle risk assessment , to motivate individuals to engage in healthy lifestyle behaviors . Study findings will guide future intervention efforts to effectively communicate genetic risk information", "OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors . RESEARCH DESIGN AND METHODS We conducted a r and omized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes . Participants were r and omly allocated to genetic testing versus no testing . Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes . Participants in the top and bottom score quartiles received individual genetic counseling before being enrolled with untested control participants in a 12-week , vali date d , diabetes prevention program . Middle-risk quartile participants were not studied further . We examined the effect of this genetic counseling intervention on patient self-reported attitudes , program attendance , and weight loss , separately comparing higher-risk and lower-risk result recipients with control participants . RESULTS The 108 participants enrolled in the diabetes prevention program included 42 participants at higher diabetes genetic risk , 32 at lower diabetes genetic risk , and 34 untested control subjects . Mean age was 57.9 ± 10.6 years , 61 % were men , and average BMI was 34.8 kg/m2 , with no differences among r and omization groups . Participants attended 6.8 ± 4.3 group sessions and lost 8.5 ± 10.1 pounds , with 33 of 108 ( 30.6 % ) losing ≥5 % body weight . There were few statistically significant differences in self-reported motivation , program attendance , or mean weight loss when higher-risk recipients and lower-risk recipients were compared with control subjects ( P > 0.05 for all but one comparison ) . CONCLUSIONS Diabetes genetic risk counseling with currently available variants does not significantly alter self-reported motivation or prevention program adherence for overweight individuals at risk for diabetes ", "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 : Genetic information , typically communicated in-person by genetic counselors , can be challenging to comprehend ; delivery of this information online - as is becoming more common - has the potential of increasing these challenges . Methods : To address the impact of the mode of delivery of genomic risk information , 300 individuals were recruited from the general public and r and omized to receive genomic risk information for type 2 diabetes mellitus in-person from a board-certified genetic counselor or online through the testing company 's website . Results : Participants were asked to indicate their genomic risk and overall lifetime risk as reported on their test report as well as to interpret their genomic risk ( increased , decreased , or same as population ) . For each question , 59 % of participants correctly indicated their risk . Participants who received their results in-person were more likely than those who review ed their results on-line to correctly interpret their genomic risk ( 72 vs. 47 % , p = 0.0002 ) and report their actual genomic risk ( 69 vs. 49 % , p = 0.002 ) . Conclusions : The delivery of personal genomic risk through a trained health professional result ed in significantly higher comprehension . Therefore , if the online delivery of genomic test results is to become more widespread , further evaluation of this method of communication may be needed to ensure the effective presentation of results to promote comprehension", "Objective : There is considerable hope that genetic susceptibility testing will motivate behavior that can prevent or reduce the risk of complex conditions such as obesity . This study examined potential behavioral consequences of such testing . Methods : Participants ( n = 249 ) were r and omly assigned to review one of four vignettes that asked them to imagine that they had been tested for their risk of becoming overweight or obese . The experimental factors were test type ( genetic versus hormone test ) and risk level ( increased versus average risk for obesity ) . Study measures included behavioral intentions and perceived behavioral control related to eating a healthy diet , as well as weight locus of control . Results : Participants assigned to the increased risk conditions indicated greater intentions to eat a healthy diet compared with participants assigned to the average risk conditions ( P risk × perceived behavioral control ( P risk × weight locus of control ( P intentions to eat a healthy diet . A three-way interaction of body mass index , family history of overweight/obesity , and assigned risk level found the greatest effects of risk feedback among those who either had a family history or a higher body mass index ( P healthier behavior . However , some individuals may be susceptible to a false reassurance effect after receiving test results indicating a lack of increased risk", "Background Proponents of consumer genetic tests cl aim that the information can positively impact health behaviors and aid in chronic disease prevention . However , the effects of disclosing genetic information on dietary intake behavior are not clear . Methods A double-blinded , parallel group , 2∶1 online r and omized controlled trial was conducted to determine the short- and long-term effects of disclosing nutrition-related genetic information for personalized nutrition on dietary intakes of caffeine , vitamin C , added sugars , and sodium . Participants were healthy men and women aged 20–35 years ( n = 138 ) . The intervention group ( n = 92 ) received personalized DNA-based dietary advice for 12-months and the control group ( n = 46 ) received general dietary recommendations with no genetic information for 12-months . Food frequency question naires were collected at baseline and 3- and 12-months after the intervention to assess dietary intakes . General linear models were used to compare changes in intakes between those receiving general dietary advice and those receiving DNA-based dietary advice . Results Compared to the control group , no significant changes to dietary intakes of the nutrients were observed at 3-months . At 12-months , participants in the intervention group who possessed a risk version of the ACE gene , and were advised to limit their sodium intake , significantly reduced their sodium intake ( mg/day ) compared to the control group ( −287.3±114.1 vs. 129.8±118.2 , p = 0.008 ) . Those who had the non-risk version of ACE did not significantly change their sodium intake compared to the control group ( 12-months : −244.2±150.2 , p = 0.11 ) . Among those with the risk version of the ACE gene , the proportion who met the targeted recommendation of 1500 mg/day increased from 19 % at baseline to 34 % after 12 months ( p = 0.06 ) . Conclusions These findings demonstrate that disclosing genetic information for personalized nutrition results in greater changes in intake for some dietary components compared to general population -based dietary advice . Trial Registration Clinical Trials.gov", "Objective To test the hypothesis that adding obesity gene feedback ( FTO ) to simple weight control advice at a life stage with raised risk of weight gain ( university ) increases readiness to control weight . Methods Individually r and omized controlled trial comparing the effect of : ( i ) simple weight control advice plus FTO feedback ( FA ) and ( ii ) simple weight control advice only ( AO ) on readiness to engage with weight control . Differences in stage of change by genotype and differential weight control behaviors were secondary outcomes . Results Of 1,016 participants r and omized , only 279 completed follow-up , yielding 90 % power to detect a small effect for readiness to control weight . As predicted , FA participants were more likely to be in the contemplation stage than AO participants ( P = 0.023 ) . Participants receiving higher-risk genetic results were at a higher stage of change than controls ( P = 0.003 ) , with a trend toward a higher stage of change than those getting lower-risk results ( P = 0.051 ) . Lower-risk results did not decrease weight control intentions compared with controls ( P = 0.55 ) . There were no group differences in adherence to recommended weight control behaviors ( P = 0.87 ) . Conclusions Adding FTO feedback to weight control advice enhanced readiness to control weight , without evidence for genetic determinism , but had no more effect on behavior than weight control advice alone", "Elevated postpr and ial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes , but existing dietary methods for controlling them have limited efficacy . Here , we continuously monitored week-long glucose levels in an 800-person cohort , measured responses to 46,898 meals , and found high variability in the response to identical meals , suggesting that universal dietary recommendations may have limited utility . We devised a machine-learning algorithm that integrates blood parameters , dietary habits , anthropometrics , physical activity , and gut microbiota measured in this cohort and showed that it accurately predicts personalized postpr and ial glycemic response to real-life meals . We vali date d these predictions in an independent 100-person cohort . Finally , a blinded r and omized controlled dietary intervention based on this algorithm result ed in significantly lower postpr and ial responses and consistent alterations to gut microbiota configuration . Together , our results suggest that personalized diets may successfully modify elevated postpr and ial blood glucose and its metabolic consequences . VIDEO ABSTRACT", "Abstract Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases , promoting better health across the life-course and increasing well-being . However , realising this potential will require the development , testing and implementation of much more effective behaviour change interventions than are used conventionally . Therefore , the aim of this study was to conduct a multi-centre , web-based , proof-of-principle study of personalised nutrition ( PN ) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population -based advice . A total of 5,562 volunteers were screened across seven European countries ; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial . Participants were r and omly assigned to one of the following intervention groups for a 6-month period : Level 0—control group — receiving conventional , non-PN advice ; Level 1—receiving PN advice based on dietary intake data alone ; Level 2—receiving PN advice based on dietary intake and phenotypic data ; and Level 3—receiving PN advice based on dietary intake , phenotypic and genotypic data . A total of 1,607 participants had a mean age of 39.8 years ( ranging from 18 to 79 years ) . Of these participants , 60.9 % were women and 96.7 % were from white-European background . The mean BMI for all r and omised participants was 25.5 kg m−2 , and 44.8 % of the participants had a BMI ≥ 25.0 kg m−2 . Food4Me is the first large multi-centre RCT of web-based PN . The main outcomes from the Food4Me study will be su bmi tted for publication during 2015", "Background Cardiovascular disease ( CVD ) remains the leading cause of death globally . Primary prevention of CVD requires cost-effective strategies to identify individuals at high risk in order to help target preventive interventions . An integral part of this approach is the use of CVD risk scores . Limitations in previous studies have prevented reliable inference about the potential advantages and the potential harms of using CVD risk scores as part of preventive strategies . We aim to evaluate short-term effects of providing different types of information about coronary heart disease ( CHD ) risk , alongside lifestyle advice , on health-related behaviours . Methods / Design In a parallel-group , open r and omised trial , we are allocating 932 male and female blood donors with no previous history of CVD aged 40–84 years in Engl and to either no intervention ( control group ) or to one of three active intervention groups : i ) lifestyle advice only ; ii ) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic characteristics ; and iii ) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic and genetic characteristics . The primary outcome is change in objective ly measured physical activity . Secondary outcomes include : objective ly measured dietary behaviours ; cardiovascular risk factors ; current medication and healthcare usage ; perceived risk ; cognitive evaluation of provision of CHD risk scores ; and psychological outcomes . The follow-up assessment takes place 12 weeks after r and omisation . The experiences , attitudes and concerns of a subset of participants will be also studied using individual interviews and focus groups . Discussion The INFORM study has been design ed to provide robust findings about the short-term effects of providing different types of information on estimated 10-year CHD risk and lifestyle advice on health-related behaviours . Trial registration Current Controlled Trials IS RCT N17721237 . Registered 12 January 2015", "This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia ( FH ) by finding a genetic mutation reduces patients ' perceptions of control over the disease and adherence to risk‐reducing behaviors . Three hundred forty‐one families , comprising 341 hypercholesterolemia prob and s and 128 adult relatives , were r and omized to one of two groups : ( a ) routine clinical diagnosis ; ( b ) routine clinical diagnosis plus genetic testing ( mutation search ing in prob and s and direct gene testing in relatives ) . The main outcome measures were perceptions of control over hypercholesterolemia , adherence to cholesterol‐lowering medication , diet , physical activity , and smoking . There was no support for the main hypothesis : finding a mutation had no impact on perceived control or adherence to risk‐reducing behavior ( all P‐values > 0.10 ) . While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack , participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level ( P = 0.02 at 6 months ) and showed a trend in believing more strongly in the efficacy of cholesterol‐lowering medication ( P = 0.06 at 6 months ) . In conclusion , finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk‐reducing behaviors . The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition , but does affect their perceptions of how control is most effectively achieved . Further work is needed to determine whether similar results will be obtained in population s with little previous awareness of their risks . © 2004 Wiley‐Liss ,", "Objective We examined the clinical utility of supplementing type 2 diabetes mellitus ( DM ) risk counseling with DM genetic test results and counseling . Research Design and Methods In this r and omized controlled trial , non-diabetic overweight/obese veteran out patients aged 21 to 65 years received DM risk estimates for lifetime risk , family history , and fasting plasma glucose , followed by either genetic test results ( CR+G ; N = 303 ) or control eye disease counseling ( CR+EYE ; N = 298 ) . All participants received brief lifestyle counseling encouraging weight loss to reduce the risk of DM . Results The mean age was 54 years , 53 % of participants were black , and 80 % were men . There was no difference between arms in weight ( estimated mean difference between CR+G vs. CR+EYE at 3 months = 0.2 kg , 95 % CI : −0.3 to 0.7 ; at 6 months = 0.4 kg , 95 % CI : −0.3 to 1.1 ) , insulin resistance , perceived risk , or physical activity at 3 or 6 months . Calorie and fat intake were lower in the CR+G arm at 3 months ( p ’s ≤ 0.05 ) but not at 6 months ( p ’s > 0.20 ) . Conclusions Providing patients with genetic test results was not more effective in changing patient behavior to reduce the risk of DM compared to conventional risk counseling . Trial registration : Clinical Trials.gov NCT01060540 http:// clinical", "Aims /hypothesisAdvances in type 2 diabetes genetics have raised hopes that genetic testing will improve disease prediction , prevention and treatment . Little is known about current physician and patient views regarding type 2 diabetes genetic testing . We hypothesised that physician and patient views would differ regarding the impact of genetic testing on motivation and adherence . Methods We surveyed a nationally representative sample of US primary care physicians and endocrinologists ( n = 304 ) , a r and om sample of non-diabetic primary care patients ( n = 152 ) and patients enrolled in a diabetes pharmacogenetics study ( n = 89 ) . Results Physicians and patients favoured genetic testing for diabetes risk prediction ( 79 % of physicians vs 80 % of non-diabetic patients would be somewhat/very likely to order/request testing , p = 0.7 ) . More patients than physicians ( 71 % vs 23 % , p motivation to adopt preventive lifestyle changes . Patients favoured genetic testing to guide therapy ( 78 % of patients vs 48 % of physicians very likely to request/recommend testing , p more motivated ’ to adhere to medications ( 72 % vs 18 % of physicians , p genetic testing before published evidence of clinical efficacy . Conclusions /interpretationDespite the paucity of current data , physicians and patients reported high expectations that genetic testing would improve patient motivation to adopt key behaviours for the prevention or control of type 2 diabetes . This suggests the testable hypothesis that ‘ genetic ’ risk information might have greater value to motivate behaviour change compared with st and ard risk information", "Genetic testing for obesity risk is increasingly available to the public but few studies have examined motivational or affective reactions . Here we report findings from a \" vignette \" study investigating reactions to \" higher-risk \" and \" average-risk \" results for the obesity-related FTO gene in two groups : a panel sample of individuals with weight concerns , for whom testing may have treatment implication s ( n = 306 , mean age = 45 years , mean BMI = 35 ) and a student sample ( n = 395 , mean age = 25 years , mean BMI = 23 ) , for whom testing would have implication s for obesity prevention . Participants were given FTO gene information that described higher-risk alleles as linked with modest weight gain and slightly higher risk of obesity . They responded to both higher- and average-risk vignettes , with order r and omized . Interest in genetic testing was high overall , and higher in panel respondents than students ( 93 % vs. 78 % would \" probably \" or \" definitely \" have the test ; P motivation to change ( d = 0.15 ; P higher negative affect ( d = 0.03 , P fatalism ( d = 0.05 , P motivation to change ( d = 0.17 , P relief about having an explanation for their body weight ( d = 0.02 , P = 0.013 ) in the higher-risk condition , but no increase in fatalism or depression . These results suggest that at the level of anticipated responses to FTO gene feedback , higher-risk results had positive motivational effects with minimal changes in negative affect or fatalism . Genetic testing has the potential to be a useful clinical or preventive tool when combined with appropriate information", "Prospect i ve registration of systematic review s promotes transparency , helps reduce potential for bias and serves to avoid unintended duplication of review s. Registration offers advantages to many stakeholders in return for modest additional effort from the research ers registering their review" ]

[ "OBJECTIVE To determine whether acetyl-L-carnitine ( ALC ) , a metabolite necessary for energy metabolism and essential fatty acid anabolism , might help attention-deficit/hyperactivity disorder ( ADHD ) . Trials in Down 's syndrome , migraine , and Alzheimer 's disease showed benefit for attention . A preliminary trial in ADHD using L-carnitine reported significant benefit . METHOD A multi-site 16-week pilot study r and omized 112 children ( 83 boys , 29 girls ) age 5 - 12 with systematic ally diagnosed ADHD to placebo or ALC in weight-based doses from 500 to 1500 mg b.i.d . The 2001 revisions of the Conners ' parent and teacher scales ( including DSM-IV ADHD symptoms ) were administered at baseline , 8 , 12 , and 16 weeks . Analyses were ANOVA of change from baseline to 16 weeks with treatment , center , and treatment-by-center interaction as independent variables . RESULTS The primary intent-to-treat analysis , of 9 DSM-IV teacher-rated inattentive symptoms , was not significant . However , secondary analyses were interesting . There was significant ( p = 0.02 ) moderation by subtype : superiority of ALC over placebo in the inattentive type , with an opposite tendency in combined type . There was also a geographic effect ( p = 0.047 ) . Side effects were negligible ; electrocardiograms , lab work , and physical exam unremarkable . CONCLUSION ALC appears safe , but with no effect on the overall ADHD population ( especially combined type ) . It deserves further exploration for possible benefit specifically in the inattentive type", "Hyperactivity is a significant problem for almost all young males affected by fragile X syndrome ( FXS ) , the most common inherited disease causing mental retardation . Therapeutical approaches are actually based on Central Nervous System ( CNS ) stimulants lacking a well defined rationale and efficacy while they further decrease the patient 's limited attention span . A pilot study on 17 fragile X male treated with L-acetylcarnitine ( LAC ) over one year , showed a significant reduction of their hyperactivity behaviour tested by the Conners Abbreviated Parent-Teacher Question naire . LAC use in FXS patients derives from the hypothesis that the biochemical and physiological properties this substance has may preserve brain activity . LAC is a small , hydrosoluble molecule that easily diffuses in the extracellular space and enters any cell in the nervous system through specific transporters . Different cerebral areas use this molecule differently to metabolize glucose and lipids to provide for ATP and neurotrasmitters synthesis . The acetyl group LAC carriers represents a key metabolic signaling element possibly mediating its effect in the CNS . The exogenous administration of LAC may affect brain activity in FXS by : I ) modulation of fuel partitioning for energy production , which at the mithocondrial level is associated with the Kreb 's cycle metabolic role in neurotransmitter synthesis ; II ) remodelling of lipid membrane in terms of LAC actively determining the production of polyunsaturated fatty acids ; III ) preferential effect on the attention component of the cholinergic system which relies on its peculiar modality of communication in the CNS . Based on the above premises an explorative , double-blind , placebo controlled , multicenter study is ongoing . A total population of 160 children from nine European centers will be enrolled . The objective of this study is to determine the effect of LAC on the hyperactive behaviour of FXS children as evaluated by the administration of the Conners Abbreviated Parent Question naire", "To determine safety and the efficacy of carnitine treatment in children with attention-deficit hyperactivity disorder ( ADHD ) . The ADHD behavior was observed by parents completing the Child Behavior Checklist ( CBCL ) and by teachers completing the Conners teacher-rating score , in a r and omized , double-blind , placebo-controlled double-crossover trial . In 13/24 boys receiving carnitine , home behavior improved as assessed with the CBCL total score ( P boys , school behavior improved as assessed with the Conners teacher-rating score ( P CBCL total and sub-scores were significantly different from those of normal Dutch boys ( P CBCL total scores compared to baseline ( P no side effects were seen . At baseline and after carnitine treatment , responders showed higher levels of plasma-free carnitine ( P acetylcarnitine ( P carnitine treatment caused in the responsive patients a decrease of 20 - 65 % ( 8 - 48 points ) as assessed by the CBCL total problem rating scale . Treatment with carnitine significantly decreased the attention problems and aggressive behavior in boys with ADHD", "Fibromyalgia is a chronic condition characterized by widespread pain , fatigue , non-restorative sleep and cognitive difficulties that affects 2 - 4 % of the general population . Recently a possible relationship between the FMR1 premutation and fibromyalgia has been pointed out . In attempt to gather more data we screened for the FMR1 CGG expansion 700 DNA sample s from unrelated fibromyalgia patients . This data might be useful for evaluating the incorporation of this test in rheumatologic procedures for women with fibromyalgia . The observed frequency of FMR1 premutation carriers ( 3 of 700 , 0.4 % ) is not significantly different from the estimated rate in the general female population ( 1/250 - 1/400 ) ( P=0.539 , P=0.716 ) . Clinical examination of the FMR1 premutation carriers identified revealed that all of them had important neurological symptoms with regard to muscular symptoms , neurocognitive alterations and neurovegetative impairments . With regard to other clinical aspects of the disease the cases apparently did not differ from the average fibromyalgia patients . On the basis of our results an FMR1 screening among fibromyalgia female patients would not be recommended . However it would be worthwhile to further evaluate the different clinical presentations that fibromyalgia patients might present based on their FMR1 premutation carrier status", "The objective of this study was to test whether a previous observed Acetyl-L-carnitine ( ALC ) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents . This was a six-week , r and omized clinical trial undertaken in an outpatient child and adolescent clinic . Subjects included 40 out patients ( 28 boys and 12 girls ) between the ages of 7–13 who met the DSM-IV-TR diagnostic criteria for ADHD . All study subjects were r and omly assigned to receive treatment using capsules of ALC doses ranging from 500 to 1,500 mg/day depending on the weight of the child plus methylpheni date at a dose of 20–30 mg/day depending on weight or Placebo plus methylpheni date at a dose of 20–30 mg/day depending on weight . The principal measure of outcome was the Teacher and Parent attention deficit/hyperactivity disorder Rating Scale- IV . No difference was observed between the two groups on the Parent and Teacher Rating Scale scores ( df = 1 ; F = 0.10 ; P = 0.74 and df = 1 ; F = 0.22 ; P = 0.63 respectively ) . Side effects consisting of headache and irritability were observed more frequently in the methylpheni date plus placebo group . The results of this study do not support the application of ALC as an adjunctive therapy to methylpheni date in children and adolescents with ADHD", "In a double-blind , placebo study , acetyl-L-carnitine was administered to 7 probable Alzheimer 's disease patients who were then compared by clinical and 31P magnetic resonance spectroscopic measures to 5 placebo-treated probable AD patients and 21 age-matched healthy controls over the course of 1 year . Compared to AD patients on placebo , acetyl-L-carnitine-treated patients showed significantly less deterioration in their Mini-Mental Status and Alzheimer 's Disease Assessment Scale test scores . Furthermore , the decrease in phosphomonoester levels observed in both the acetyl-L-carnitine and placebo AD groups at entry was normalized in the acetyl-L-carnitine-treated but not in the placebo-treated patients . Similar normalization of high-energy phosphate levels was observed in the acetyl-L-carnitine-treated but not in the placebo-treated patients . This is the first direct in vivo demonstration of a beneficial effect of a drug on both clinical and CNS neurochemical parameters in AD", "Attention deficit hyperactivity disorder ( ADHD ) is a frequent behavioral problem in young boys with fragile X syndrome ( FXS ) , and its treatment is critical for improving social ability . The short‐term efficacy of stimulant medications like methylpheni date ( MPH ) is well established in children with ADHD . FXS boys treated with MPH have improved attention span and socialization skills ; however their mood becomes unstable at higher doses . Therefore , alternative pharmacological treatment of ADHD symptoms is desirable . A recent study showed that carnitine has a beneficial effect on the hyperactive – impulsive behavior in boys with ADHD without side effects . Our previous placebo‐controlled trial indicated that L‐acetylcarnitine ( LAC ) reduces hyperactivity in FXS boys . The objective of this study was to determine the efficacy of LAC in a larger sample of FXS boys with ADHD . The study design was r and omized , double blind placebo controlled , parallel , and multicenter ( with eight centers involved in Italy , France , and Spain ) . Sixty‐three FXS males with ADHD ( aged 6–13 years ) were enrolled ; 7 patients dropped out , 56 completed the one‐year treatment , and 51 were included in the statistical analysis . Both groups improved their behavior , showing that psychosocial intervention has a significant therapeutic effect . However , we observed a stronger reduction of hyperactivity and improvement of social behavior in patients treated with LAC , compared with the placebo group , as determined by the Conners ' Global Index Parents and the Vinel and Adaptive Behavior Scale . Our results show that LAC ( 20–50 mg/kg/day ) represents a safe alternative to the use of stimulant drugs for the treatment of ADHD in FXS children . © 2008 Wiley‐Liss ," ]

[ "Abstract Background The aim of the study was to compare ligation anopexy ( LA ) and conventional hemorrhoidectomy ( CH ) in treatment of second- and third-degree hemorrhoids . Methods A prospect i ve controlled r and omized clinical trial included 100 patients who underwent CH ( CH group ) and 100 patients who underwent LA ( LA group ) . A detailed history was taken from all the patients . The effectiveness , safety , postoperative complications , operative time , length of hospital stay , time until first bowel movement , time until return to work , and postoperative pain score were assessed . Results There was no significant difference between groups regarding age , sex , and preoperative symptoms . The LA group had significantly shorter operative times , earlier first bowel movement , and an earlier return to work/activities . The postoperative pain score in the LA group was significantly lower than that in the CH group on days 1 , 3 , 7 , and 14 after surgery . There was no significant difference between groups as regards postoperative complications . Conclusions LA is safe , and as effective as CH in the treatment of grade II and grade III hemorrhoids , with shorter operative times , earlier mobilization , and lower postoperative pain scores", "The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement aims to improve the reporting of r and omized controlled trials ( RCTs ) ; however , it lacks guidance on the reporting of patient-reported outcomes ( PROs ) , which are often inadequately reported in trials , thus limiting the value of these data . In this article , we describe the development of the CONSORT PRO extension based on the method ological framework for guideline development proposed by the Enhancing the Quality and Transparency of Health Research ( EQUATOR ) Network . Five CONSORT PRO checklist items are recommended for RCTs in which PROs are primary or important secondary end points . These recommendations urge that the PROs be identified as a primary or secondary outcome in the abstract , that a description of the hypothesis of the PROs and relevant domains be provided ( ie , if a multidimensional PRO tool has been used ) , that evidence of the PRO instrument 's validity and reliability be provided or cited , that the statistical approaches for dealing with missing data be explicitly stated , and that PRO-specific limitations of study findings and generalizability of results to other population s and clinical practice be discussed . Examples and an up date d CONSORT flow diagram with PRO items are provided . It is recommended that the CONSORT PRO guidance supplement the st and ard CONSORT guidelines for reporting RCTs with PROs as primary or secondary outcomes . Improved reporting of PRO data should facilitate robust interpretation of the results from RCTs and inform patient care", " This multicentre r and omized clinical trial studied how symptoms improved after either stapled anopexy or diathermy excision of haemorrhoids", "AIM The study aim ed in a multicentric r and omized controlled trial to define the role of a more extensive mucosal resection on recurrence of mucosal prolapse in patients with Stage III haemorrhoids undergoing stapled haemorrhoidopexy . METHOD In all , 135 patients were r and omized to treatment with a PPH-01/03 ( Ethicon EndoSurgery ) or an EEA ( Covidien ) stapler . They were review ed after a minimum follow-up of 4 years to determine the rate of recurrent mucosal prolapse and general condition ( wellness evaluation score ) . Postoperative bowel dysfunction was assessed using the Rome III criteria . RESULTS Eighty-seven ( 65 % ) of the 135 patients ( 48 in the EEA stapler group and 37 in the PPH group ) were available for long-term follow-up . The two groups were comparable for age , gender and duration of follow-up ( mean 49.3 ± 5.4 months and 49.0 ± 5.3 months respectively ) . In the EEA group , 11 ( 23 % ) patients had some degree of recurrent prolapse compared with 12 ( 32 % ) in the PPH group ( P = 0.409 ) . Persistence of anal bleeding was significantly higher in the PPH group ( P = 0.04 ) while the postoperative Haemorrhoid Symptom Score was significantly better in the EEA group ( 1.73 ± 1.65 vs 3.17 ± 1.94 , P 0.001 ) . The wellness evaluation score was significantly better in the EEA group ( 1.2 ± 1.27 vs 0.6 ± 1.0 , P = 0.028 ) . Furthermore , 7 ( 15 % ) of the patients in the EEA group complained of some evacuation disturbance compared with 13 ( 36 % ) in the PPH group ( P = 0.021 ) . CONCLUSION The study failed to demonstrate any significant difference in the long-term recurrence rate of Stage III haemorrhoids using EEA or PPH . Nevertheless , use of the larger volume EEA provides better symptom resolution compared with PPH", "Objective : Unlike excisional haemorrhoidectomy , stapled anopexy ( SA ) , which does not involve radical excision , has theoretical advantages , thus offering potential patient benefits . We compared the clinical efficacy , safety and patient acceptability of SA , with closed haemorrhoidectomy ( CH ) . Patients and methods : 182 patients with symptomatic haemorrhoids ( grade s II , III , IV ) were r and omly assigned to receive SA or CH and were followed for up to 1 year ( 6 , 12 , 24 , 48 weeks ) after operation . Postoperative pain , symptom control , complications , re-treatment rates , patient satisfaction , and quality of life were compared on an intention-to-treat basis . Results : Postoperative pain in the SA group ( n = 91 ) was significantly lower ( p = 0.004 , Mann – Whitney U test ) . At 1 year there were no significant differences in the symptom load , symptom severity or the disease severity between the two groups . Overall complication rates were similar but faecal urgency was reported more frequently following SA ( p = 0.093 , Fisher ’s exact test ) . Despite a similar rate of residual symptoms , prolapse control was better with CH ( p = 0.087 , Fisher ’s exact test ) , and more patients in the SA group required re-treatment for residual prolapse at 1 year ( p = 0.037 , Fisher ’s exact test ) . However , more patients rated SA as an excellent operation at 6 and 12 weeks ( p = 0.008 and 0.033 , binary logistic regression ) and were willing to undergo a repeat procedure if required ( p = 0.018 , Fisher ’s exact test ) . Conclusion : Stapled anopexy offers a significantly less painful alternative to excisional haemorrhoidectomy and achieves a higher patient acceptability . Although the overall symptom control and safety are similar in the majority of the patients , the re-treatment rate for recurrent prolapse at 1 year is higher following SA when compared to CH", "Summary Background Two commonly performed surgical interventions are available for severe ( grade II – IV ) haemorrhoids ; traditional excisional surgery and stapled haemorrhoidopexy . Uncertainty exists as to which is most effective . The eTHoS trial was design ed to establish the clinical effectiveness and cost-effectiveness of stapled haemorrhoidopexy compared with traditional excisional surgery . Methods The eTHoS trial was a large , open-label , multicentre , parallel-group , pragmatic r and omised controlled trial done in adult participants ( aged 18 years or older ) referred to hospital for surgical treatment for grade II – IV haemorrhoids . Participants were r and omly assigned ( 1:1 ) to receive either traditional excisional surgery or stapled haemorrhoidopexy . R and omisation was minimised according to baseline EuroQol 5 dimensions 3 level score ( EQ-5D-3L ) , haemorrhoid grade , sex , and centre with an automated system to stapled haemorrhoidopexy or traditional excisional surgery . The primary outcome was area under the quality of life curve ( AUC ) measured with the EQ-5D-3L descriptive system over 24 months , assessed according to the r and omised groups . The primary outcome measure was analysed using linear regression with adjustment for the minimisation variables . This trial is registered with the IS RCT N registry , number IS RCT N80061723 . Findings Between Jan 13 , 2011 , and Aug 1 , 2014 , 777 patients were r and omised ( 389 to receive stapled haemorrhoidopexy and 388 to receive traditional excisional surgery ) . Stapled haemorrhoidopexy was less painful than traditional excisional surgery in the short term and surgical complication rates were similar between groups . The EQ-5D-3L AUC score was higher in the traditional excisional surgery group than the stapled haemorrhoidopexy group over 24 months ; mean difference −0·073 ( 95 % CI −0·140 to −0·006 ; p=0·0342 ) . EQ-5D-3L was higher for stapled haemorrhoidopexy in the first 6 weeks after surgery , the traditional excisional surgery group had significantly better quality of life scores than the stapled haemorrhoidopexy group . 24 ( 7 % ) of 338 participants who received stapled haemorrhoidopexy and 33 ( 9 % ) of 352 participants who received traditional excisional surgery had serious adverse events . Interpretation As part of a tailored management plan for haemorrhoids , traditional excisional surgery should be considered over stapled haemorrhoidopexy as the surgical treatment of choice . Funding National Institute for Health Research Health Technology Assessment programme", "Introduction The aim of the study was to compare short- and medium-term outcomes of transanal haemorrhoidal dearterialisation ( THD ) versus stapled haemorrhoidopexy ( SH ) for the treatment of second- and third-degree haemorrhoids . Methods Patients with second- or third-degree haemorrhoids who failed conservative treatment were r and omly allocated to THD or SH . Preoperative and postoperative symptoms , postoperative pain , time until return to normal activities , complications , patient satisfaction and recurrence rates were all assessed prospect ively . Patients were followed up at 2 , 8 months and when the study was completed . Results Twenty-eight patients ( 43 % third degree ) underwent THD and 24 ( 38 % third degree ) underwent SH . There were no significant differences in terms of postoperative pain , expected pain and analgesia requirements , but more THD patients returned to work within 4 days ( P sub-mucosal haematoma after surgery , one SH patient occlusion of the rectal lumen and two rectal bleeding . At 8-month follow-up , two SH patients complained of faecal urgency . At 38-month follow-up ( range 33–48 months ) , all short-term complications resolved . Patient satisfaction ( “ excellent/good outcome ” , THD 89 vs. SH 87 % ) and recurrence rate ( THD 14 vs. SH 13 % ) were similar in the two groups . Conclusions Short-term results although similar seem to suggest SH may result in increased morbidity while return to work is quicker after THD . Medium-term results demonstrate that THD and SH have similar effectiveness", "PURPOSE To evaluate efficacy and safety of superior rectal artery embolization of hemorrhoidal disease as a first-line invasive treatment . MATERIAL S AND METHODS This prospect i ve study was conducted between 2014 and 2015 on 25 consecutive patients ( 16 men and 9 women with a mean age of 53 y [ range , 30 - 76 y ] ) with grade II-III hemorrhoids refractory to medical treatment . A transfemoral superselective superior rectal artery branch embolization was performed using 2- and 3-mm diameter microcoils . Over the following 12 months , clinical outcomes were evaluated using the French bleeding score , Goligher prolapse score , visual analog scale ( VAS ) score for pain , quality -of-life score . The primary endpoint was relief of symptoms by 12 months based on a 2-point minimum improvement on VAS score and bleeding score . RESULTS At 12 months after embolization , clinical success was obtained in 18 patients ( 72 % ) , 8 of whom had 2 embolizations . VAS score decreased from 4.6 to 2.3 ( P bleeding score decreased from 5.5 to 2.3 ( P Quality -of-life and prolapse scores also showed improvement ( P complications . Complete clinical failure was observed in 7 patients . After coil embolization , the collateral supply to the hemorrhoidal cushions was significantly related to any recurrence ( P = .001 ) . CONCLUSIONS Hemorrhoidal artery coil embolization was found to be a safe and effective treatment for grade II-III hemorrhoids", "Objective An improved underst and ing of the pathophysiology of haemorrhoids has result ed in the introduction of new surgical techniques including stapled haemorrhoidopexy ( SH ) . This r and omized controlled trial compared the long‐term effectiveness of SH with rubber b and ligation ( RBL ) in the treatment of grade II circumferential symptomatic haemorrhoids", "Introduction Exact data on the prevalence of hemorrhoids are rare . Therefore , we design ed a study to investigate the prevalence of hemorrhoids and associated risk factors in an adult general population . Methods Between 2008 and 2009 , consecutive patients were included in a prospect i ve study . They attended the Austrian national wide health care program for colorectal cancer screening at four medical institutions . A flexible colonoscopy and detailed examination were conducted in all patients . Hemorrhoids were defined according to a st and ardized grading system . Independent variables included baseline characteristics , sociodemographic data , and health status . Potential risk factors were calculated by univariate and multivariate analysis . Results Of 976 participants , 380 patients ( 38.93 % ) suffered from hemorrhoids . In 277 patients ( 72.89 % ) , hemorrhoids were classified as grade I , in 70 patients ( 18.42 % ) as grade II , in 31 patients ( 8.16 % ) as grade III , and in 2 patients ( 0.53 % ) as grade IV . One hundred seventy patients ( 44.74 % ) complained about symptoms associated with hemorrhoids , whereas 210 patients ( 55.26 % ) reported no symptoms . In the univariate and multivariate analysis , body mass index ( BMI ) had a significant effect on the occurrence of hemorrhoids with p = 0.0391 and p = 0.0282 , respectively . Even when correcting for other potential risk factors , an increase in the BMI of one increased the risk of hemorrhoids by 3.5 % . Conclusion Hemorrhoids occur frequently in the adult general population . Notably , a considerable number of people with hemorrhoids do not complain about symptoms . In addition , a high BMI can be regarded as an independent risk factor for hemorrhoids", "Aim The long‐term results of stapled haemorrhoidopexy for prolapsed haemorrhoids were assessed using uniform methods to acquire data and pre‐set definitions of failure , recurrence , residual symptoms and impaired continence ", "Background Traditional treatment of fourth-degree haemorrhoidal disease ( HD ) is conventional haemorrhoidectomy and is frequently associated with significant pain and morbidity . In recent years , the use of transanal haemorrhoidal dearterialization ( THD ) for the treatment of HD has increased . The procedure aims to decrease the arterial blood flow to the haemorrhoids . Moreover , since a rectal mucopexy to treat the prolapsing component has become part of the THD technique , this treatment is also indicated for more advanced HD . The aim of this study was to assess the possible role of THD in the treatment of fourth-degree HD . Methods All patients with non-fibrotic fourth-degree HD were offered the THD procedure with mucopexy . Excision of skin tags was added to THD and mucopexy , when needed . A specific score was used to assess HD severity , ranging from 0 ( no HD ) to 20 ( worst HD ) . The mean preoperative score was 18.1 ± 1.8 . Results Thirty-five consecutive patients ( mean age 50.4 ± 13.8 years ; 19 men ) with fourth-degree HD were prospect ively enroled . An average of 6 arteries were identified and transfixed . Mucopexy was achieved with a 3–6 sector plication of rectal mucosa . Mean operating time was 33 ± 12 min . No intraoperative complications were recorded . Postoperative morbidity included 3 ( 8.6 % ) haemorrhoidal thromboses ( 1 requiring surgery ) and 2 ( 5.7 % ) episodes of bleeding ( 1 requiring surgical haemostasis ) . Five patients ( 14.3 % ) had urinary retention requiring catheterization . At a median follow-up of 10 months ( range 2–28 months ) , symptoms had resolved or significantly improved in 33 ( 94 % ) patients . Nine patients ( 25.7 % ) reported irregular bleeding , 3 patients ( 8.6 % ) mild anal pain , 4 patients ( 11.4 % ) transient anal burning and 4 patients ( 11.4 % ) tenesmus . Ten patients ( 28.6 % ) experienced some degree of residual prolapse , significant only in 2 ( 5.7 % ) who required further surgery . There was no anorectal stenosis , and no faecal incontinence was reported . At a median follow-up of 10 months , the symptomatic score was 2.5 ± 2.5 ( P Transanal haemorrhoidal dearterialization seems to be a safe and effective treatment for fourth-degree HD providing a significant improvement of symptoms for the majority of patients . When present , persisting symptoms are mostly transient , occasional or limited in severity , and only a very few patients require further intervention . Larger series and longer follow-up to further assess the role of THD in this challenging group of pts", "Purpose This study was design ed to demonstrate the usefulness of a method of regional anesthesia for circular stapler anopexy for prolapsing hemorrhoids . Methods Thirty-three patients consented to stapled anopexy under perianal local anesthesia . Eighteen patients with stapled anopexy under general anesthesia were controls . The perianal block was applied with 40 ml of ropivacaine , 4.75 mg/ml , injected immediately peripheral to the external sphincter . A submucosal block with 15 ml of ropivacaine , 2 mg/ml , was added after applying the pursestring suture . Postoperative pain was rated by the patient for 14 days by using a ten-point visual analogue scale . Patients also su bmi tted a preoperative and postoperative ( 3–6 months ) symptom question naire to rate anal symptoms . Results No operation was converted to general anesthesia . Operation time was similar in both groups . All patients in the local anesthesia group were pain free at discharge . The sums of pain scores during 14 days for daily average pain and peak pain were similar in both groups ( average pain 23 ( local anesthesia ) vs. 35 ( general anesthesia ) ; peak pain 39 ( local anesthesia ) vs. 50 ( general anesthesia ) ; P > 0.05 ) . The preoperative symptom scores were 7.8 ( local anesthesia ) vs. 8.9 ( general anesthesia ) points , and the follow-up scores were 2.2 ( local anesthesia ) and 2.7 ( general anesthesia ) , a significant improvement ( P = 0.001 ) in both groups but not different between groups . Conclusions A perianal local block is easy to apply and has a high degree of acceptance among patients . The operation time , postoperative pain , and success rates of the operation equaled those of stapled anopexy performed under general anesthesia . The advantages are quicker turnover between cases and simpler management of pain-free postoperative patients in day surgery", "The aim of the study was to compare the early results in 52 patients r and omly allocated to undergo either stapled or open hemorrhoidectomy . Seventy-four patients with grade III and IV hemorrhoids were r and omly allocated to undergo either stapled ( 37 patients ) or open ( 37 patients ) hemorrhoidectomy . Stapled hemorrhoidectomy was performed with the use of a circular stapling device . Open hemorrhoidectomy was accomplished according to the Milligan-Morgan technique . Postoperative pain was assessed by means of a visual analogue scale ( V.A.S. ) . Recovery evaluation included return to pain-free defecation and normal activities . A 6-month clinical follow-up and a 17.5 ( 10 to 27)-month median telephone follow-up was obtained in all patients . Operation time for stapled hemorrhoidectomy was shorter ( median 25 [ range 15 to 49 ] minutes versus 30 [ range 20 to 44 ] minutes , p = 0.041 ) . Median ( range ) V.A.S. scores in the stapled group were significantly lower ( V.A.S. score after 4 hours : 4 [ 2 to 6 ] versus 5 [ 2 to 8 ] , p = 0.001 ; V.A.S. score after 24 hours : 3 [ 1 to 6 ] versus 5 [ 3 to 7 ] , p = 0.000 ; V.A.S. score after first defecation : 5 [ 3 to 8 ] versus 7 [ 3 to 9 ] , p = 0.000 ) . Resumption of pain-free defecation was significantly faster in the stapled group ( 10 [ 6 to 14 ] days vs 12 [ 9 to 19 ] days , p = 0.001 ) . At follow-up 4 weeks and 6 months postoperatively the median ( range ) symptom severity score was similar in both groups ( 1 [ 0 to 2 ] versus 0 [ 0 to 3 ] , p = 0.150 and 0 [ 0 to 2 ] versus 0 [ 0 to 2 ] , p = 0.731 ) . At long-term follow-up occasional pain was present in 6/37 ( 16.2 ) patients in the stapled group and 7/37 ( 18.9 % ) in the Milligan-Morgan group ( p = 1.000 ) ; episodes of bleeding were reported by 8/37 ( 21.6 % ) patients in the stapled group and 5/37 ( 13.5 % ) patients in the Milligan-Morgan group ( p = 0.542 ) . No problems related to continence and defecation were reported in either group . Patients were satisfied with the operation in 33/37 ( 89.2 % ) cases in the stapled group and 31/37 ( 83.8 % ) cases in the Milligan-Morgan group ( p = 0.735 ) . Hemorrhoidectomy with a circular staple device is easy to perform and achieves better results than the Milligan-Morgan technique in terms of postoperative pain and recovery . Comparable results are obtained at long-term follow-up", "BACKGROUND Optimal surgical intervention for low- grade haemorrhoids is unknown . Rubber b and ligation ( RBL ) is probably the most common intervention . Haemorrhoidal artery ligation ( HAL ) is a novel alternative that may be more efficacious . OBJECTIVE The comparison of HAL with RBL for the treatment of grade II/III haemorrhoids . DESIGN A multicentre , parallel-group r and omised controlled trial . PERSPECTIVE UK NHS and Personal Social Services . SETTING 17 NHS Trusts . PARTICIPANTS Patients aged ≥ 18 years presenting with grade II/III ( second- and third-degree ) haemorrhoids , including those who have undergone previous RBL . INTERVENTIONS HAL with Doppler probe compared with RBL . OUTCOMES Primary outcome - recurrence at 1 year post procedure ; secondary outcomes - recurrence at 6 weeks ; haemorrhoid severity score ; European Quality of Life-5 Dimensions , 5-level version ( EQ-5D-5L ) ; Vaizey incontinence score ; pain assessment ; complications ; and cost-effectiveness . RESULTS A total of 370 participants entered the trial . At 1 year post procedure , 30 % of the HAL group had evidence of recurrence compared with 49 % after RBL [ adjusted odds ratio ( OR ) = 2.23 , 95 % confidence interval ( CI ) 1.42 to 3.51 ; p = 0.0005 ] . The main reason for the difference was the number of extra procedures required to achieve improvement/cure . If a single HAL is compared with multiple RBLs then only 37.5 % recurred in the RBL arm ( adjusted OR 1.35 , 95 % CI 0.85 to 2.15 ; p = 0.20 ) . Persistence of significant symptoms at 6 weeks was lower in both arms than at 1 year ( 9 % HAL and 29 % RBL ) , suggesting significant deterioration in both groups over the year . Symptom score , EQ-5D-5L and Vaizey score improved in both groups compared with baseline , but there was no difference between interventions . Pain was less severe and of shorter duration in the RBL group ; most of the HAL group who had pain had mild to moderate pain , resolving by 3 weeks . Complications were low frequency and not significantly different between groups . It appeared that HAL was not cost-effective compared with RBL . In the base-case analysis , the difference in mean total costs was £ 1027 higher for HAL . Quality -adjusted life-years ( QALYs ) were higher for HAL ; however , the difference was very small ( 0.01 ) result ing in an incremental cost-effectiveness ratio of £ 104,427 per additional QALY . CONCLUSIONS At 1 year , although HAL result ed in fewer recurrences , recurrence was similar to repeat RBL . Symptom scores , complications , EQ-5D-5L and continence score were no different , and patients had more pain in the early postoperative period after HAL . HAL is more expensive and unlikely to be cost-effective in terms of incremental cost per QALY . LIMITATIONS Blinding of participants and site staff was not possible . FUTURE WORK The incidence of recurrence may continue to increase with time . Further follow-up would add to the evidence regarding long-term clinical effectiveness and cost-effectiveness . The polysymptomatic nature of haemorrhoidal disease requires a vali date d scoring system , and the data from this trial will allow further assessment of validity of such a system . These data add to the literature regarding treatment of grade II/III haemorrhoids . The results dovetail with results from the eTHoS study [ Watson AJM , Hudson J , Wood J , Kilonzo M , Brown SR , McDonald A , et al. Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease ( eTHoS ) : a pragmatic , multicentre , r and omised controlled trial . Lancet 2016 , in press . ] comparing stapled haemorrhoidectomy with excisional haemorrhoidectomy . Combined results will allow expansion of analysis , allowing surgeons to tailor their treatment options to individual patients . TRIAL REGISTRATION Current Controlled Trials IS RCT N41394716 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 88 . See the NIHR Journals Library website for further project information", "The original operation for open hemorrhoidectomy as described by Milligan – Morgan is no longer used . There is a great variation in how the operation is described in clinical trials . A number of modifications have been proposed attempting to reduce postoperative pain . An anatomical plane for the dissection was first described by Loder and Phillips [ 1 ] . They encountered small fibers passing from the internal sphincter to the anal cushions and emphasized the importance of dividing these fibers close to the cushions leaving an intact surface over the internal sphincter . Gerjy et al. described a subdermal fascia continuing into a membrane covering the internal sphincter , which was easily identified after incision of the skin of the pedicle [ 2 ] . In addition , Loder and Phillips were the first to suggest diathermy dissection and coagulation [ 1 ] . A better knowledge of hemorrhoidal vascular anatomy , demonstrating , how the arterial supply to the hemorrhoids crosses the rectal wall , has reduced the need for pedicle ligation . Seow-Chonen et al. demonstrated in a r and omized study that diathermy dissection , when compared to scissor dissection , result ed in less postoperative pain and Bessa et al. showed how diathermy coagulation of the pedicle was superior to ligation in reducing postoperative pain [ 3 , 4 ] . We adapted these principles and also minimized excision of the skin and the hemorrhoid . In addition , we left a part of the hemorrhoid intra-anally to reduce any impact on anal continence . We called this modification “ minimal open hemorrhoidectomy ” ( MOH ) . Material s and", "Background There is a lack of st and ardised outcomes for haemorrhoidal disease making comparison between trials difficult . A need for a very well vali date d severity score is essential to facilitate meta- analysis of comparative studies , enabling evidence -based clinical practice . Methods The Hubble trial provides a large cohort of patients with haemorrhoidal disease r and omised to rubber b and ligation ( RBL ) or haemorrhoidal artery ligation . The haemorrhoid severity score ( HSS ) was collected on each patient at baseline , 6 weeks and 1 year after intervention . This allows for the responsiveness of the HSS instrument to be examined and compared with a more specific instrument , the Vaizey incontinence score ( also collected ) . Responsiveness was tested using four methods ( effect size , st and ardised response means ( SRM ) , significance of change , and responsiveness statistic ) . Results The four tests of responsiveness demonstrated that the HSS was more responsive to changes in the patient ’s health status following both of the interventions compared to the Vaizey question naire . For example , between baseline and 6 weeks , the RBL intervention effect size scores and SRM calculations indicated a non-significant small amount of change ( 0.20 and 0.16 respectively ) . However , using the HSS , the effect size and SRM demonstrated a large magnitude of change ( 1.12 and 1.01 , respectively ) which was significant . Similar results were observed at 1 year . Significance of change scores and the index of responsiveness were also higher for the HSS question naire than the Vaizey across both treatment modalities . Conclusions The HSS is a highly responsive tool for the detection of changes in haemorrhoid symptoms . It should form an essential patient-reported outcome tool for future studies on haemorrhoidal disease", "AIM This multicentre study , based on the largest patient population ever published , aims to evaluate the efficacy of Doppler-guided transanal haemorrhoidal dearterialization ( THD Doppler ) in the treatment of symptomatic haemorrhoids and to identify the factors predicting failure for an effective mid-term outcome . METHOD Eight hundred and three patients affected by Grade II ( 137 , 17.1 % ) , III ( 548 , 68.2 % ) and IV ( 118 , 14.7 % ) symptomatic haemorrhoidal disease underwent THD Doppler , with a rectal mucopexy in patients with haemorrhoidal prolapse . The disease was assessed through a specifically design ed symptom question naire and scoring system . A uni- and multivariate analyses of the potential predictive factors for failure were performed . RESULTS The morbidity rate was 18.0 % , represented mainly by pain or tenesmus ( 106 patients , 13.0 % ) . Acute bleeding requiring surgical haemostasis occurred in seven patients ( 0.9 % ) . No serious or life-threatening complications occurred . After a mean follow-up period of 11.1 ± 9.2 months , the overall success rate was 90.7 % ( 728 patients ) , with a recurrence of haemorrhoidal prolapse , bleeding , and both symptoms in 51 ( 6.3 % ) , 19 ( 2.4 % ) and 5 ( 0.6 % ) patients , respectively . Sixteen out of 47 patients undergoing re-operation had a conventional haemorrhoidectomy . All the symptoms were significantly improved in each domain of the score ( P absence of morbidity and performance of a distal Doppler-guided dearterialization were associated with a better outcome . CONCLUSION THD Doppler is a safe and effective therapy for haemorrhoidal disease . If this technique is to be employed , an accurate distal Doppler-guided dearterialization and a tailored mucopexy are m and atory to contain and reduce the symptoms" ]

[ "OBJECTIVE To evaluate associations between psychosocial and social-environmental variables and diabetes self-management , and diabetes control . RESEARCH DESIGN AND METHODS Baseline data from a type 2 diabetes self-management r and omized trial with 463 adults having elevated BMI ( M = 34.8 kg/m2 ) were used to investigate relations among demographic , psychosocial , and social-environmental variables ; dietary , exercise , and medication-taking behaviors ; and biologic outcomes . RESULTS Self-efficacy , problem solving , and social-environmental support were independently associated with diet and exercise , increasing the variance accounted for by 23 and 19 % , respectively . Only diet contributed to explained variance in BMI ( β = −0.17 , P = 0.0003 ) and self-rated health status ( β = 0.25 , P only medication-taking behaviors contributed to lipid ratio ( total – to – HDL ) ( β = −0.20 , P = 0.0001 ) and A1C ( β = −0.21 , P enhancing self-efficacy , problem solving , and social-environmental support to improve self-management of diabetes", "OBJECTIVE This study examined the impact of a 6-month , empowerment-based diabetes self-management support ( DSMS ) intervention on clinical outcomes , self-care behaviors , and quality of life ( QOL ) compared to a 6-month control period . METHODS This control-intervention cohort study recruited 77 African-American adults with type 2 diabetes . Baseline , 6-month , and 12-month assessment s measured A1C , weight , body mass index ( BMI ) , blood pressure , lipids , self-care behaviors , and QOL . During the control period , participants received weekly educational newsletters . During the intervention period , participants attended weekly DSMS groups as frequently as they needed . Sessions were guided by participants ' self-management questions and concerns , and also emphasized experiential learning , coping , problem-solving , and goal - setting . RESULTS The control period found significant improvements for diastolic BP ( p serum cholesterol ( p following a healthy diet ( p monitoring blood glucose ( p A1C ( p weight ( p BMI ( p LDL ( p A1C ( p empowerment-based , DSMS intervention is promising for improving and /or maintaining diabetes-related health , particularly A1C . PRACTICAL IMPLICATION S Incorporating empowerment principles in DSMS interventions may be useful for supporting patients ' self-management efforts in \" real-world \" setting", "OBJECTIVE To conduct a 1-year r and omized clinical trial to evaluate a remote comprehensive diabetes self-management education ( DSME ) intervention , Diabetes TeleCare , administered by a dietitian and nurse/certified diabetes educator ( CDE ) in the setting of a federally qualified health center ( FQHC ) in rural South Carolina . RESEARCH DESIGN AND METHODS Participants were recruited from three member health centers of an FQHC and were r and omized to either Diabetes TeleCare , a 12-month , 13-session curriculum delivered using telehealth strategies , or usual care . RESULTS Mixed linear regression model results for repeated measures showed a significant reduction in glycated hemoglobin ( GHb ) in the Diabetes TeleCare group from baseline to 6 and 12 months ( 9.4 ± 0.3 , 8.3 ± 0.3 , and 8.2 ± 0.4 , respectively ) compared with usual care ( 8.8 ± 0.3 , 8.6 ± 0.3 , and 8.6 ± 0.3 , respectively ) . LDL cholesterol was reduced at 12 months in the Diabetes TeleCare group compared with usual care . Although not part of the original study design , GHb was reduced from baseline to 12 and 24 months in the Diabetes TeleCare group ( 9.2 ± 0.4 , 7.4 ± 0.5 , and 7.6 ± 0.5 , respectively ) compared with usual care ( 8.7 ± 0.4 , 8.1 ± 0.4 , and 8.1 ± 0.5 , respectively ) in a post hoc analysis of a subset of the r and omized sample who completed a 24-month follow-up visit . CONCLUSIONS Telehealth effectively created access to successfully conduct a 1-year remote DSME by a nurse CDE and dietitian that improved metabolic control and reduced cardiovascular risk in an ethnically diverse and rural population", " This article describes the design and implementation of an online diabetes self-management intervention for a sample of inner-city African Americans with diabetes . Study participants were r and omly assigned to the treatment ( 26 ) and control ( 21 ) conditions . The results indicate that treatment group participants were more likely to achieve positive outcomes in terms of lowered hemoglobin A1c and body mass index measurements than were control group members . These findings support the development of telehealth interventions to promote effective chronic disease management in medically underserved communities", "OBJECTIVE The Informatics for Diabetes Education and Telemedicine ( IDEATel ) project r and omized ethnically diverse underserved older adults with diabetes to a telemedicine intervention or usual care . Intervention participants had lower A1C levels over 5 years . New analyses were performed to help better underst and this difference . RESEARCH DESIGN AND METHODS IDEATel r and omized Medicare beneficiaries with diabetes ( n = 1,665 ) to receive home video visits with a diabetes educator and upload glucose levels every 4–6 weeks or usual care ( 2000–2007 ) . Annual measurements included BMI , A1C ( primary outcome ) , and completion of question naires . Mixed-model analyses were performed using r and om effects to adjust for clustering within primary care physicians . RESULTS At baseline , A1C levels ( mean ± SD ) were 7.02 ± 1.25 % in non-Hispanic whites ( n = 821 ) , 7.58 ± 1.78 % in non-Hispanic blacks ( n = 248 ) , and 7.79 ± 1.68 % in Hispanics ( n = 585 ) . Over time , lower A1C levels were associated with more glucose uploads ( P = 0.02 ) and female sex ( P = 0.002 ) . Blacks , Hispanics , and insulin-users had higher A1C levels than non-Hispanic whites ( P 0.0001 ) . BMI was not associated with A1C levels . Blacks and Hispanics had significantly fewer uploads than non-Hispanic whites over time . Hispanics had the highest baseline A1C levels and showed the greatest improvement in the intervention , but , unlike non-Hispanic whites , Hispanics did not achieve A1C levels cohort of underserved older adults with diabetes . The IDEATel telemedicine intervention was associated with improvement in glycemic control , particularly in Hispanics , who had the highest baseline A1C levels , suggesting that telemedicine has the potential to help reduce disparities in diabetes management", "OBJECTIVE The objective of this study was to evaluate the impact of a problem-based empowerment patient education program specifically tailored for urban African Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS The study used a r and omized controlled trial ( RCT ) pretest/post-test design with repeated measures . Patients were r and omly assigned to either a six-week intervention group or a six-week wait-listed control group . After completing the six sessions , patients were invited to participate in one of two follow-up conditions ; attend a monthly support group or receive a monthly phone call from a nurse . Assessment measures included HbA1C , lipids , blood pressure , weight , self-management behavior and psychosocial adaptation . RESULTS Both control and intervention patients showed a broad array of small-to-modest positive changes during the six-week RCT . These gains were maintained or improved upon during the one-year follow-up period . For patients in the two follow-up conditions , a positive correlation was seen between the number of follow-up contacts and their one-year HbA1C values . CONCLUSIONS We believe that results of this study can be attributed to volunteer bias , study effects ( ie , providing study data on several occasions to patients and their physicians during the one-year study period ) , and impact of the interventions . However , the study design does not allow us to examine the relative impact of these three factors on the patient improvements seen over the one-year study period", "OBJECTIVES We evaluated lifestyle interventions for diabetic persons who live in rural communities . METHODS We conducted a 12-month r and omized clinical trial ( n = 152 ) of \" intensive-lifestyle \" ( modeled after the NIH Diabetes Prevention Program ) and \" reimbursable-lifestyle \" ( intensive-lifestyle intervention delivered in the time allotted for Medicare reimbursement for diabetes education related to nutrition and physical activity ) interventions with usual care as a control . RESULTS Modest weight loss occurred by 6 months among intensive-lifestyle participants and was greater than the weight loss among usual-care participants ( 2.6 kg vs 0.4 kg , P lost 2 kg or more than usual-care participants ( 49 % vs 25 % , P weight change were observed between reimbursable-lifestyle and usual-care participants . Glycated hemoglobin was reduced among all groups ( P Improvement in both weight and glycemia was attainable by lifestyle interventions design ed for persons who had type 2 diabetes and lived in rural communities" ]

[ "OBJECTIVES Complaints of fatigue are frequent in patients with obstructive sleep apnea ( OSA ) ; however , the impact of continuous positive airway pressure ( CPAP ) on fatigue remains unclear . METHODS Fifty-nine men and women with OSA were r and omly assigned to therapeutic or placebo CPAP in a double-blind fashion for a 3-week intervention period . Four outcome measures were assessed : ( 1 ) fatigue/vigor measured with the Multidimensional Fatigue Symptom Inventory -- Short Form ( MFSI-sf ) , the ( 2 ) fatigue and ( 3 ) vigor subscales of the Profile of Mood States -- Short Form ( POMS ) , and ( 4 ) the Epworth Sleepiness Scale ( ESS ) . Data were analyzed using repeated- measures analysis of variance . RESULTS Compared with patients receiving placebo CPAP , those patients treated with therapeutic CPAP showed significant reductions in the apnea-hypopnea index , as well as decreases in both measures of fatigue and increases in vigor ( P values sleepiness scores were not observed in the entire sample ( P > 0.05 ) ; however , in a subset of patients with excessive sleepiness at the onset of treatment , ESS scores were significantly reduced with use of therapeutic CPAP ( P CPAP significantly reduced fatigue and increased energy in patients with OSA . Therapeutic CPAP significantly reduced daytime sleepiness in patients who reported excessive sleepiness at the onset of treatment", "BACKGROUND Cognitive complaints are reported frequently after breast cancer treatments . Their association with neuropsychological ( NP ) test performance is not well-established . METHODS Early-stage , posttreatment breast cancer patients were enrolled in a prospect i ve , longitudinal , cohort study prior to starting endocrine therapy . Evaluation included an NP test battery and self-report question naires assessing symptoms , including cognitive complaints . Multivariable regression models assessed associations among cognitive complaints , mood , treatment exposures , and NP test performance . RESULTS One hundred eighty-nine breast cancer patients , aged 21 - 65 years , completed the evaluation ; 23.3 % endorsed higher memory complaints and 19.0 % reported higher executive function complaints ( > 1 SD above the mean for healthy control sample ) . Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments ( P = .01 ) , poorer NP verbal memory performance ( P = .02 ) , and higher depressive symptoms ( P NP visual memory performance ( P = .03 ) and higher depressive symptoms ( P combined chemotherapy and radiation treatment ( P = .05 ) approached statistical significance . CONCLUSIONS About one in five post-adjuvant treatment breast cancer patients had elevated memory and /or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms ; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints . These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance , although their etiology and biology appear to be multifactorial , motivating further transdisciplinary research", "This investigation evaluates two common measures of cancer-related fatigue , one multidimensional/retrospective and one unidimensional/same day . Fifty-two African American survivors of diverse cancers completed fatigue visual analogue scales once daily , and the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) once weekly , for four weeks . Zero-order correlations showed retrospective fatigue was significantly related to average , peak , and most recent same-day fatigue . Multilevel r and om coefficient modeling showed unidimensional fatigue shared the most variance with the MFSI-SF 's General subscale for three weeks , and with the Vigor subscale for one week . Research ers and clinicians may wish to prioritize multidimensional measures when assessing cancer-related fatigue , if appropriate", "OBJECTIVE Insomnia is frequently comorbid with other medical and psychological disorders . This secondary data analysis investigated whether an Internet-delivered cognitive behavioral therapy for insomnia ( CBT-I ) intervention could also reduce comorbid psychological and fatigue symptoms . METHOD Data from a pilot r and omized controlled trial ( RCT ) testing the efficacy of Internet-delivered CBT-I relative to a waitlist control was used to examine changes in symptoms of depression , anxiety , mental health quality of life ( QOL ) , and fatigue . RESULTS Group by time interactions from repeated measures analyses revealed significant post intervention improvements in Internet participants ( n = 22 ) relative to control participants ( n = 22 ) on all psychological symptoms , mental health QOL , and fatigue . A small post hoc sub sample of Internet participants with mild or moderate depression also showed large effect size changes in these constructs ( depression , anxiety , mental health QOL , and fatigue ) . CONCLUSION Internet-delivered CBT-I appears to not only improve sleep but also reduce comorbid psychological and fatigue symptoms", "Women with breast cancer are one of the largest groups of cancer survivors . This research examined whether breast cancer has a long-term impact on quality of life ( QOL ) by comparing 5-year disease-free survivors to age-matched controls and by comparing women who sustained a recurrence to disease-free survivors . Controls were recruited using the neighborhood control methodology . QOL ( physical , emotional , social , and spiritual ) was assessed during in-person interviews . There were no differences between disease-free survivors ( n = 267 ) and controls ( n = 187 ) on many indicators of QOL . However , survivors reported more difficulties with physical functioning , more physical symptoms , and more faith than did controls ( all ps worse QOL on most indices , less positive affect , more general fatigue , and more intrusive and avoidant thoughts ( all ps indices of marriage , work experiences , or spirituality . These findings suggest that the QOL of long-term survivors who remain disease-free is comparable to that of women their age with the exception of physical functioning . Women who sustain a recurrence suffer an impaired QOL in some , but not all , domains", "Purpose Fatigue is one of the most disturbing complaints of cancer patients and is often the reason for discontinuing treatment . This r and omized controlled study tested the hypothesis that increased morning bright light , compared to dim light , would result in less fatigue in women with breast cancer undergoing chemotherapy . Methods Thirty-nine women newly diagnosed with stage I – III breast cancer were r and omized to either bright white light ( BWL ) or dim red light ( DRL ) treatment and were instructed to use the light box for 30 min every morning throughout the first four cycles of chemotherapy . The Multidimensional Fatigue Symptom Inventory was administered prior to the start of chemotherapy ( baseline ) , during the chemotherapy treatment week of cycle 1 ( C1TW ) , the last week ( recovery week ) of cycle 1 ( C1RW ) , the chemotherapy treatment week of cycle 4 ( C4TW ) , and the last week ( recovery week ) of cycle 4 ( C4RW ) . Results The DRL group reported increased fatigue at C1TW ( p = 0.003 ) and C4TW ( p increases in fatigue levels in the DRL group were not mediated through nor associated with changes in sleep or in circadian rhythms as measured with wrist actigraphy . Conclusions The results of this study suggest that morning bright light treatment may prevent overall fatigue from worsening during chemotherapy . Although our hypothesis that overall fatigue would improve with bright light treatment was not supported , the lack of deterioration in total fatigue scores suggests that bright morning light may be a useful intervention during chemotherapy for breast cancer", "OBJECTIVE In April 2005 a phase III r and omized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints : increase of lean body mass , decrease of resting energy expenditure ( REE ) , increase of total daily physical activity , decrease of interleukin-6 and tumor necrosis factor-alpha , and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) . METHODS All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid , carbocysteine , and vitamins A , C , and E , all orally . Patients were then r and omized to one of the following five arms : 1 ) medroxyprogesterone acetate/megestrol acetate ; 2 ) pharmacologic nutritional support containing eicosapentaenoic acid ; 3 ) L-carnitine ; 4 ) thalidomide ; or 5 ) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide . Treatment duration was 4 mo . The sample comprised 475 patients . RESULTS By January 2007 , 125 patients , well balanced for all clinical characteristics , were included . No severe side effects were observed . As for efficacy , an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3 , 4 , and 5 , whereas arm 2 showed a significant worsening of lean body mass , REE , and MFSI-SF . Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1 , 3 , and 5 versus arm 2 . A significant inferiority of arm 2 versus arms 3 , 4 , and 5 for the primary endpoints lean body mass , REE , and MFSI-SF was observed on the basis of t test for changes . CONCLUSION The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen . The study is still in progress and the final results should confirm these data", "Background While exercise acts to combat inflammation and aging , the ability to exercise may itself be compromised by inflammation and inflammation 's impact on muscle recovery and joint inflammation . A number of nutritional supplements have been shown to reduce inflammation and improve recovery . The purpose of the current investigation was to examine the effect of a multi-nutrient supplement containing branched chain amino acids , taurine , anti-inflammatory plant extracts , and B vitamins on inflammatory status , endothelial function , physical function , and mood in middle-aged individuals . Methods Thirty-one healthy and active men ( N = 16 , mean age 56 ± 6.0 yrs ) and women ( N = 15 , mean age = 52 ± 7.5 yrs ) participated in this investigation . Subjects completed one 28 day cycle of placebo supplementation and one 28 day cycle of multi-nutrient supplementation ( separated by a one week washout period ) in a balanced , r and omized , double-blind , cross-over design . Subjects completed weekly perceptual logs ( PROMIS-57 , KOOS ) and pre- and post- testing around the supplementation period . Testing consisted of brachial artery flow mediated dilation ( FMD ) , blood measures , and physical performance on vertical jump , h and grip strength , and balance ( dispersion from center of pressure ) . Significance for the investigation was p ≤ 0.05 . Results IL-6 significantly decreased in both men ( from 1.2 ± 0.2 to 0.7 ± 0.4 pg·mL-1 ) and women ( from 1.16 ± 0.04 to 0.7 ± 0.4 pg·mL-1 ) . Perceived energy also improved for both men ( placebo : 1.8 ± 0.7 ; supplement : 3.7 ± 0.8 AUC ) and women ( placebo : 1.2 ± 0.7 ; supplement : 2.8 ± 0.8 AUC ) . Alpha-1-antichymotrypsin ( from 108.9 ± 38.6 to 55.5 ± 22.2 ug·mL-1 ) , Creatine Kinase ( from 96 ± 34 to 67 ± 23 IU·L-1 ) , general pain , and joint pain decreased in men only , while anxiety and balance ( from 0.52 ± 0.13 to 0.45 ± 0.12 cm ) improved in women only . Men showed increased performance in vertical jump power ( from 2642 ± 244 to 3134 ± 282 W ) and grip strength ( from 42.1 ± 5.9 to 48.5 ± 4.9 kg ) . Conclusions A multi-nutrient supplement is effective in improving inflammatory status in both men and women , markers of pain , joint pain , strength , and power in men only , and both anxiety and balance ( a risk factor for hip fracture ) in women . Therefore , a multi-nutrient supplement may help middle-aged individuals to prolong physical function and maintain a healthy , active lifestyle", "Objective : To examine the hypothesis that young adults with major depressive disorder ( MDD ) would show increased affective bias to painful and nonpainful experimental heat stimuli , as evidence d by an increased responsiveness to warm and hot temperatures . Pain and depression often occur together . Pain is both a sensation and an affective experience . Similarly , depression is associated frequently with somatic symptoms as well as emotional dysphoria . Existing evidence indicates that MDD may be associated with altered pain processing . However , the extent to which alterations in experimentally controlled heat pain sensations are related to increased affective bias in MDD is unknown . Method : Grade d nonnoxious and noxious heat stimuli were delivered r and omly with a thermode applied to the volar surface of the left arm of 15 unmedicated subjects with current MDD and 15 age- and gender-matched healthy comparison subjects . MDD and non-MDD subjects rated the intensity and unpleasantness of all stimuli . Results : Two main results were observed . First , MDD relative to non-MDD subjects showed decreased heat pain thresholds . Second , a significantly increased affective bias ( unpleasantness/intensity ) was observed in subjects with MDD , particularly over the range of nonnoxious heat stimuli . This bias was independent of the change in sensory pain thresholds . Conclusion : These findings represent corroborative evidence of abnormal affective heat pain processing in young adults with MDD , and suggest that MDD is associated with “ emotional allodynia , ” a qualitatively altered negative emotional response to normally nonaversive thermal stimuli . MDD = major depressive disorder", "Chronic inflammation is one of the main features of cancer cachexia . Experimental and clinical studies showed that cyclooxygenase-2 inhibitors , such as celecoxib , may be beneficial in counteracting major symptoms of this devastating syndrome . We carried out a prospect i ve phase II clinical trial to test the safety and effectiveness of an intervention with the COX-2 inhibitor celecoxib ( 300 mg/day for 4 months ) on key variables of cachexia ( lean body mass , resting energy expenditure , serum levels of proinflammatory cytokines , and fatigue ) in patients with advanced cancer at different sites . A sample of 24 patients was enrolled from January to December 2008 and all were deemed assessable . A significant increase of lean body mass and a significant decrease of TNF-α were observed . Moreover , an improvement of grip strength , quality of life , performance status , and Glasgow prognostic score was shown . There were no grade 3/4 toxicities . Patient compliance was very good ; no patient had to reduce the celecoxib dosage nor interrupt treatment . Our results showed that the COX-2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia . Although the treatment of cancer cachexia , a multifactorial syndrome , is more likely to yield success with a multitargeted approach ; in the present study , we were able to show that a treatment , such as celecoxib , addressing a single target , albeit very important as chronic inflammation , could have positive effects . Therefore , phase III clinical trials are warranted to test the efficacy and safety of celecoxib", "OBJECTIVE Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease . PATIENTS AND METHODS On the basis of our previously published studies and clinical experience , we have developed an innovative approach consisting of diet with high polyphenol content ( 400 mg ) , p.o . pharmaconutritional support enriched with n - 3 fatty acids ( eicosapentaenoic acid and docosahexaenoic acid ) 2 cans ( 237 mL each ) per day , medroxiprogesterone acetate 500 mg/d , antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d , and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d . The treatment is administered for 16 weeks . The following variables are evaluated : ( a ) clinical variables ( stage and Eastern Cooperative Oncology Group performance status ) ; ( b ) nutritional variables ( lean body mass , appetite , and resting energy expenditure ) ; ( c ) laboratory variables ( serum levels of proinflammatory cytokines , C-reactive protein , and leptin and blood levels of reactive oxygen species and antioxidant enzymes ) ; and ( d ) quality of life variables ( European Organization for Research and Treatment of Cancer QLQ-C30 , EQ-5Dindex , and EQ-5DVAS ) . A phase II nonr and omized study has been design ed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress . RESULTS As of January 2004 , 28 patients have been enrolled : 25 patients were evaluable and 14 of them have completed the treatment ( 20 patients have completed 2 months of treatment ) . As for clinical response , five patients improved , three patients remained unchanged , and six patients worsened . The Eastern Cooperative Oncology Group performance status ( grade ) 1 remained unchanged . As for nutritional/functional variables , the lean body mass increased significantly at 2 and 4 months . As for laboratory variables , reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly . As for quality of life , it comprehensively improved after treatment . CONCLUSIONS The treatment has been shown to be effective for clinical response , increase of lean body mass , decrease of reactive oxygen species and proinflammatory cytokines , and improvement of quality of life . The treatment has been shown to be safe with good compliance of patients . The study is in progress ( 14 further patients will be included )", "BACKGROUND Patients with chronic heart failure ( HF ) and with elevated depression symptoms are at greater risk of morbidity and mortality . Somatic symptoms of depression are particularly prevalent in HF and are related to worse disease prognosis . T'ai chi practice is related to increased emotional well-being in various clinical population s ; however , relatively little is known about t'ai chi 's effects on somatic versus cognitive symptom dimensions of depression in HF . PURPOSE The objective of the study was to measure whether a t'ai chi intervention effectively reduces somatic and /or cognitive symptoms of depression in patients with HF . METHODS Patients with HF were assigned to either t'ai chi training ( n=16 ) or a usual-care group ( n=12 ) . At baseline and after the 12-week intervention period , participants were evaluated for changes in depressive symptoms using Beck Depression Inventory ( BDI ) total scores ( BDI-t ) and subcategorized scores of BDI-somatic ( BDI-s ) and BDI-cognitive ( BDI-c ) , and for symptoms of fatigue using the Multidimensional Fatigue Symptom Inventory-Short Form . RESULTS Patients with HF in the t'ai chi group compared to the usual-care group had reduced BDI-s ( p≤0.017 ) , but not BDI-c ( p=0.50 ) scores from pre- to postintervention . Although t'ai chi did not significantly reduce fatigue , changes in physical fatigue ( p≤0.05 ) were independently associated with changes in BDI-t scores . CONCLUSIONS T'ai chi practice reduced somatic symptoms of depression , which have been linked to worse prognosis in HF . Reductions in fatigue appear to explain some but not all of the reductions in somatic symptoms of depression ", "OBJECTIVE To determine the feasibility and efficacy of a physical activity behavioural change intervention in managing cancer-related fatigue among gynaecological cancer survivors during and post anti-cancer treatments . METHODS A two arm , single blind , r and omised controlled trial was conducted within the Northern Irel and regional Cancer Centre . Thirty three sedentary gynaecological cancer survivors ( stage I-III ; ≤3 years post diagnosis ) , experiencing cancer-related fatigue ( mild-severe ) took part . Participants were r and omly assigned to a behavioural change , moderate intensity physical activity intervention ( n=16 ) or a Contact Control group ( n=17 ) . The primary outcome was fatigue ( Multidimensional Fatigue Symptom Inventory-Short Form and Functional Assessment in Chronic Illness Therapy-Fatigue subscale ) . Secondary outcomes included quality of life , physical functioning , positive and negative affect , depression , body composition , sleep dysfunction and self-reported physical activity . Feasibility was assessed based on the recruitment rate , programme and physical activity adherence and participants ' programme evaluation , including optional focus groups ( n=16 ) . RESULTS Twenty five percent of eligible women took part ( 33/134 ) . Participants were 8.7 ( SD=9.1 ) months post diagnosis , with a mean age of 53 ( SD=10.3 ) years . The majority of the sample had a diagnosis of ovarian ( n=12 ) or endometrial cancer ( n=11 ) . Significant differences favouring the intervention group were observed for fatigue at 12 weeks and 6 months follow-up ( 12 week : mean difference=-11.06 ; 95 % confidence interval (CI)=-21.89 to -0.23 ; effect size (d)=0.13 ; p=0.046 ; 6 month : mean difference=-19.48 ; 95 % CI=-19.67 to -19.15 ; effect size (d)=0.20 ; p=0.01 ) . A mean of 10 calls ( SD=1.2 calls ) were delivered to the Physical Activity Group , and 10 ( SD=1.6 calls ) to the CC group . The intervention was positively perceived based on exit question naire and focus group findings . CONCLUSIONS A physical activity behavioural change intervention for gynaecological cancer survivors is feasible in terms of participants ' programme adherence and evaluation , and the intervention demonstrates improvements in fatigue . However , confirmation in the form of a larger fully powered RCT is warranted", "OBJECTIVE The concept of symptom clusters is relatively new in cancer patients ' symptom management . This study , which spanned four cycles of chemotherapy , combined three commonly seen pre-treatment symptoms in cancer patients ( i.e. sleep disturbances , fatigue and depression ) into one symptom cluster , to explore the associations between pre-treatment cluster categories and longitudinal profiles of these same symptoms during chemotherapy . METHODS This was a prospect i ve study . Seventy-six women with newly diagnosed stage I-III breast cancer , scheduled to receive at least four cycles of adjuvant or neoadjuvant anthracycline-based chemotherapy participated . Data were collected at seven time points before and during treatment . Sleep quality was measured with the Pittsburgh Sleep Quality Index . Fatigue was measured with the Multidimensional Fatigue Symptom Inventory -- Short Form . Depressive symptoms were measured with the Center of Epidemiological Studies --Depression . Patients were divided into three groups based on the number of symptoms they experienced before the start of chemotherapy ( i.e. no symptoms , 1 - 2 symptoms or all three symptoms ) and a symptom cluster index ( SCI ) was computed . RESULTS All women reported worse sleep , more fatigue and more depressive symptoms during treatment compared with baseline ( all p's worse symptoms during treatment compared with those who began with fewer symptoms ( all p's sleep disturbances , greater fatigue and more depressive symptoms during chemotherapy . Specific interventions for these pre-treatment symptoms may improve the frequency and severity of these same symptoms during chemotherapy , when they are most severe and most disruptive to quality of life", "PURPOSE A phase III , r and omized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass ( LBM ) , resting energy expenditure ( REE ) , and fatigue- and relevant secondary endpoints : appetite , quality of life , grip strength , Glasgow Prognostic Score ( GPS ) and proinflammatory cytokines . PATIENTS AND METHODS Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were r and omly assigned to one of five treatment arms : arm 1 , medroxyprogesterone ( 500 mg/day ) or megestrol acetate ( 320 mg/day ) ; arm 2 , oral supplementation with eicosapentaenoic acid ; arm 3 , L-carnitine ( 4 g/day ) ; arm 4 , thalidomide ( 200 mg/day ) ; and arm 5 , a combination of the above . Treatment duration was 4 months . RESULTS Analysis of variance showed a significant difference between treatment arms . A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints . An analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) significantly increased in arm 5 . REE decreased significantly and fatigue improved significantly in arm 5 . Appetite increased significantly in arm 5 ; interleukin (IL)-6 decreased significantly in arm 5 and arm 4 ; GPS and Eastern Cooperative Oncology Group performance status ( ECOG PS ) score decreased significantly in arm 5 , arm 4 , and arm 3 . Toxicity was quite negligible , and was comparable between arms . CONCLUSION The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite , IL-6 , GPS , and ECOG PS score was the combination regimen that included all selected agents", "OBJECTIVE Insomnia is a common complaint among cancer survivors . Fortunately , cognitive-behavioral therapy for insomnia ( CBT-I ) has been shown to be an effective treatment in this population . However , it is rarely implemented given its limited availability . To address this barrier , we examined the ability of an easily accessible online CBT-I program to improve insomnia symptoms in cancer survivors . METHODS Twenty-eight cancer survivors with insomnia were r and omly assigned to either an Internet insomnia intervention ( n = 14 ) or to a waitlist control group ( n = 14 ) . The online program , Sleep Healthy Using The Internet , delivers the primary components of CBT-I ( sleep restriction , stimulus control , cognitive restructuring , sleep hygiene , and relapse prevention ) . Pre- and post- assessment data were collected via online question naires and daily sleep diaries . RESULTS Participants in the Internet group showed significant improvements at post- assessment compared with those in the control group in overall insomnia severity ( F(1,26 ) = 22.8 ; p sleep efficiency ( F(1,24 ) = 11.45 ; P = 0.002 ) , sleep onset latency ( F(1,24 ) = 5.18 ; P = 0.03 ) , soundness of sleep ( F(1,24 ) = 9.34 ; P = 0.005 ) , restored feeling upon awakening ( F(1,24 ) = 11.95 ; P = 0.002 ) , and general fatigue ( F(1,26 ) = 13.88 ; P = 0.001 ) . Although other group × time interactions were not significant , overall adjusted effect sizes for all sleep variables as well as for fatigue , depression , anxiety , and quality of life ranged from small to large . CONCLUSIONS CBT-I delivered through an interactive , individually tailored Internet intervention may be a viable treatment option for cancer survivors experiencing insomnia", "BACKGROUND Safe , effective interventions to improve cancer-related fatigue ( CRF ) are needed because it remains a prevalent , distressing , and activity-limiting symptom . Based on pilot data , a phase III trial was developed to evaluate the efficacy of American ginseng on CRF . METHODS A multisite , double-blind trial r and omized fatigued cancer survivors to 2000 mg of American ginseng vs a placebo for 8 weeks . The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) at 4 weeks . Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided , two- sample t test . Toxicities were evaluated by self-report and the National Cancer Institute 's Common Terminology Criteria for Adverse Events ( CTCAE ) provider grading . RESULTS Three hundred sixty-four participants were enrolled from 40 institutions . Changes from baseline in the general subscale of the MFSI-SF were 14.4 ( st and ard deviation [ SD ] = 27.1 ) in the ginseng arm vs 8.2 ( SD = 24.8 ) in the placebo arm at 4 weeks ( P = .07 ) . A statistically significant difference was seen at 8 weeks with a change score of 20 ( SD = 27 ) for the ginseng group and 10.3 ( SD = 26.1 ) for the placebo group ( P = .003 ) . Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment . Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms . CONCLUSIONS Data support the benefit of American ginseng , 2000 mg daily , on CRF over an 8-week period . There were no discernible toxicities associated with the treatment . Studies to increase knowledge to guide the role of ginseng to improve CRF are needed", "The Rotterdam Symptom Checklist ( RSCL ) is a well-known instrument for the assessment of symptom-related distress among cancer patients . Despite its broad application , the utility of the RSCL with patients of some cancers is hindered by the omission of several important physical symptoms and method ological limitations of previous validation studies . The aims of the present study were to modify the RSCL through the addition of several physical symptoms and to subsequently vali date the modified version of the Rotterdam Symptom Checklist ( RSCL-M ) with a heterogeneous sample of cancer patients from the United States . A total of 1,005 male and female cancer patients from two midwestern states completed the RSCL-M and several other self-report instruments . Results indicated that the RSCL-M is a reliable and valid instrument for use with cancer patients in the United States and is sensitive to differences in physical distress across groups expected to have distinct symptom-related distress profiles", "STUDY OBJECTIVE Fatigue and sleep disturbances are two of the most common and distressing symptoms of cancer patients . A relationship between the two symptoms was reported in symptom cluster studies ; however , only subjective measurements of sleep were examined and most studies were cross-sectional . In this study of women with breast cancer undergoing chemotherapy , we explored the longitudinal relationship between fatigue and sleep measured both subjectively and objective ly . DESIGN Prospect i ve study . Data were collected at 7 time points : before ( baseline ) and during the 3 weeks of cycle 1 and cycle 4 chemotherapy . PARTICIPANTS Ninety-seven women with newly diagnosed stage I-III breast cancer who were scheduled to receive at least four 3-week cycles of chemotherapy . MEASUREMENT AND RESULTS Objective sleep parameters were measured with an Actillume actigraph ( Ambulatory Monitoring Inc. ) . Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index ( PSQI ) . Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) . Fatigue became worse during both cycles of chemotherapy ( P-values Subjective sleep quality was poor at baseline and remained unchanged throughout treatment . Objective nighttime and daytime total sleep time increased compared to baseline during the treatment administration week of both cycles ; daytime total wake time decreased during the treatment week of both cycles and during the last 2 week of cycle 4 . Mixed model results revealed that fatigue was positively associated with total PSQI scores and with objective measures of total nap time , and negatively associated with total wake time during the day ( all P-values poor sleep and objective measures of daytime sleepiness , but not with nocturnal sleep as measured with actigraphy . This relationship between fatigue and sleep warrants further studies to explore their possible common underlying etiology", "Background Fatigue is one of the most common and distressing complaints among cancer patients , not only during radiation and chemotherapy , but also for months to years after the completion of treatment . Fatigue interferes with patients ’ daily lives , reduces their quality of life , and is often a significant reason why patients discontinue treatment . We hypothesized that some of the fatigue may be related to disrupted circadian rhythms and low light exposure . The main objective of this study therefore was to investigate the association between fatigue and light exposure among patients with breast cancer . Methods As part of a larger , ongoing prospect i ve study on fatigue , sleep , and circadian rhythms in patients with breast cancer , an analysis of 63 women newly diagnosed with stage I – IIIA breast cancer and scheduled to receive four cycles of adjuvant or neoadjuvant anthracycline-based chemotherapy was conducted . Data were collected before and during weeks 1 , 2 , and 3 of cycle 1 and cycle 4 . Fatigue was assessed using the Short Form of Multidimensional Fatigue Symptom Inventory . Light exposure was recorded with a wrist actigraph . Results There were significant correlations between fatigue levels and light exposure ( r=−0.28 to −0.45 ) within both cycle 1 and cycle 4 , such that higher levels of fatigue were associated with less light exposure . There were also significant correlations between changes in light exposure and changes in fatigue within the first 2 weeks of each cycle ( r=−0.28 to −0.52 ) . Conclusions Increased fatigue was significantly correlated with decreased light exposure among patients with breast cancer . Although the cause and effect of exacerbated fatigue and decreased light exposure can not be confirmed by the current study , and lower light exposure may just in part be due to the fatigued patients spending less time outdoors in bright light , two hypotheses are proposed about the mechanisms by which light may alleviate the fatigue of patients with breast cancer . These results suggest the need for prospect i ve intervention studies of light therapy for breast-cancer-related fatigue", "Purpose : To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support , antioxidants , and drugs , all given orally , in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress . Patients and Methods : An open early-phase II study was design ed according to the Simon two-stage design . The integrated treatment consisted of diet with high polyphenols content ( 400 mg ) , antioxidant treatment ( 300 mg/d α-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C ) , and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA ( eicosapentaenoic acid and docosahexaenoic acid ) , 500 mg/d medroxyprogesterone acetate , and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib . The treatment duration was 4 months . The following variables were evaluated : ( a ) clinical ( Eastern Cooperative Oncology Group performance status ) ; ( b ) nutritional [ lean body mass ( LBM ) , appetite , and resting energy expenditure ] ; ( c ) laboratory [ proinflammatory cytokines and leptin , reactive oxygen species ( ROS ) and antioxidant enzymes ] ; ( d ) quality of life ( European Organization for Research and Treatment of Cancer QLQ-C30 , Euro QL-5D , and MFSI-SF ) . Results : From July 2002 to January 2005 , 44 patients were enrolled . Of these , 39 completed the treatment and were assessable . Body weight increased significantly from baseline as did LBM and appetite . There was an important decrease of proinflammatory cytokines interleukin-6 ( IL-6 ) and tumor necrosis factor-α , and a negative relationship worthy of note was only found between LBM and IL-6 changes . As for quality of life evaluation , there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30 , Euro QL-5DVAS , and multidimensional fatigue symptom inventory-short form scores . At the end of the study , 22 of the 39 patients were “ responders ” or “ high responders . ” The minimum required was 21 ; therefore , the treatment was effective and more importantly was shown to be safe . Conclusion : The efficacy and safety of the treatment have been shown by the study ; therefore , a r and omized phase III study is warranted . ( Cancer Epidemiol Biomarkers Prev 2006;15(5):1030–4" ]

[ "Background Enhanced secondary preventive follow-up after stroke or transient ischemic attack ( TIA ) is necessary for improved adherence to recommendations regarding blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) levels . We investigated whether nurse-led , telephone-based follow-up was more efficient than usual care at improving BP and LDL-C levels at 12 months after hospital discharge . Methods We r and omized 537 patients to either nurse-led , telephone-based follow-up ( intervention ) or usual care ( control ) . BP and LDL-C measurements were performed at 1 month ( baseline ) and 12 months post-discharge . Intervention group patients who did not meet target values at baseline received additional follow-up , including titration of medication and lifestyle counselling , to reach treatment goals ( BP , LDL-C 2.5 mmol/L ) . Results At 12 months , mean systolic BP , diastolic BP and LDL-C was 3.3 ( 95 % CI 0.3 to 6.3 ) mmHg , 2.3 mmHg ( 95 % CI 0.5 to 4.2 ) and 0.3 mmol/L ( 95 % CI 0.1 to 0.4 ) lower in the intervention group compared to controls . Among participants with values above the treatment goal at baseline , the difference in systolic BP and LDL-C was more pronounced ( 8.0 mmHg , 95 % CI 4.0 to 12.1 , and 0.6 mmol/L , 95 % CI 0.4 to 0.9 ) . A larger proportion of the intervention group reached the treatment goal for systolic BP ( 68.5 vs. 56.8 % , p = 0.008 ) and LDL-C ( 69.7 % vs. 50.4 % , p Nurse-led , telephone-based secondary preventive follow-up , including medication adjustment , was significantly more efficient than usual care at improving BP and LDL-C levels by 12 months post-discharge . Trial Registration IS RCT N Registry IS RCT", "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", "Nir Z , Zolotogorsky Z , Sugarman H : Structured nursing intervention versus routine rehabilitation after stroke . Am J Phys Med Rehabil 2004;83:522–529 . Objective : The goal of this study was to examine the effect of a structured , comprehensive nursing intervention on the course of rehabilitation over the first 6 mos after a first-ever stroke . Design : Intervention ( experimental ) study . The participants were 155 elderly stroke survivors who were admitted to a geriatric rehabilitation department . Stratified r and om sampling generated intervention and control groups . The intervention was design ed to work together with the routine rehabilitation program and consisted of 12 consecutive weekly meetings . The control group received only the routine rehabilitation program . Study variables were measured at entry to study and after 3- and 6-mo intervals . Results : Although there were no significant differences between the two groups at entry to study , at 3 and 6 mos after stroke , the intervention group showed better scores than the control group in functional status ( FIM ™ instrument ) , depression ( Geriatric Depression Scale ) , self-perceived health , self-esteem , and dietary adherence . Conclusion : The nursing intervention had both short- and long-term effects on functional , psychological , and emotional variables . Serious consideration should be given to implementing comprehensive nursing interventions during rehabilitation tailored to meet the specific needs of stroke survivors and their caregivers", "The aim was to study if health outcome and secondary prevention were satisfactory 1 year after stroke and if nurse-led interventions 3 months after stroke could have impact . Design was a r and omized controlled open trial in a 1-year population . Primary outcome was health status 1 year after stroke . One month after stroke , survivors were r and omized into intervention group ( IG ) with follow-up by a specialist nurse ( SN ) after 3 months ( n = 232 ) , and control group ( CG ) with st and ard care ( n = 227 ) , all to be followed up 1 year after stroke . At the first follow-up , patients grade d their health , replied to the EuroQol-5 Dimensions ( EQ-5D ) health outcome questions , health problems were assessed , and supportive counseling was provided in the IG . Health problems requiring medical interventions were primarily referred to a general practitioner ( GP ) . One year after stroke , 391 survivors were followed up . Systolic blood pressure ( BP ) had decreased in IG ( n = 194 ) from median 140 to 135 ( P = .05 ) , but about half were above the limit 139 in both groups . A larger proportion ( 22 % ) had systolic BP > 155 in the CG ( n = 197 ) than in the IG ( 14 % ; P = .05 ) . In the IG , 62 % needed referrals compared with the 75 % in the CG ( P = .009 ) . Forty percent in the IG and 52.5 % in the CG ( P = .04 ) reported anxiety/depression . In the IG , 75 % and 67 % in the CG rated their general health as fairly good or very good ( P = .05 ) . Although nurse-led interventions could have some effect , the results were not optimal . A more powerful strategy could be closer collaboration between the SN and a stroke clinician , before referring to primary care", "Background : Few population -based studies with long-term follow-up have compared risk of recurrent stroke and cardiac events after first ischemic stroke . The relative risk of these two outcomes may inform treatment decisions . Methods : In the population -based Northern Manhattan Study , first ischemic stroke patients age 40 or older were prospect ively followed for recurrent stroke , myocardial infa rct ion ( MI ) , and cause-specific mortality . Fatal cardiac events were defined as death secondary to MI , congestive heart failure , sudden death/arrhythmia , and cardiopulmonary arrest . Risk of events ( with 95 % CIs ) was calculated using Kaplan – Meier survival analysis and adjusted for sex and age using Cox proportional hazard models . Results : Mean age ( n = 655 ; median follow-up 4.0 years ) was 69.7 ± 12.7 years . The risk of recurrent stroke was more than twice that of cardiac events ( including nonfatal MI ) at 30 days and approximately twice cardiac risk at 5 years . The age- and sex-adjusted 5-year risk of fatal or nonfatal recurrent stroke was 18.3 % ( 14.8 to 21.7 % ) , and the 5-year risk of MI or fatal cardiac event was 8.6 % ( 6.0 to 11.2 % ) . The adjusted 5-year risk of nonfatal stroke ( 14.8 % , 11.6 to 17.9 % ) was approximately twice as high as fatal cardiac events ( 6.4 % , 4.1 to 8.6 % ) and four times higher than risk of fatal stroke ( 3.7 % , 2.1 to 5.4 % ) . Conclusions : Cardiac mortality is nearly twice as high as mortality owing to recurrent stroke , but long-term risk of all stroke , fatal or nonfatal , is approximately twice the risk of all cardiac events . The high risk of nonfatal recurrent stroke reinforces the importance of therapies aim ed at preventing stroke recurrence in addition to preventing cardiac events", "INTRODUCTION Many stroke survivors would benefit from modification of their lifestyle in order to reduce their risk of recurrent stroke . We investigated if tailored smoking cessation advice would yield a higher smoking cessation rate and a higher rate with sustained abstinence in ex-smokers in the intervention group than among controls . MATERIAL AND METHODS Patients admitted with an acute stroke or a transient ischaemic attack were included in a r and omised controlled trial focusing on control of lifestyle risk factors and hypertension . Here , we report the intervention focused on smoking cessation . We used multiple logistic regression analysis to identify patient characteristics associated with smoking cessation . Analyses were by intention to treat excluding those who died or suffered severe disease . RESULTS We included 254 patients with a history of smoking . Two years after inclusion , 15 of 57 ( 26 % ) baseline smokers in the intervention group had stopped smoking versus eight of 56 ( 14 % ) among controls ( p = 0.112 ) . Living with a partner ( p = 0.012 ) , having at least ten years of education ( p = 0.012 ) , and not being exposed to smoking at home ( p = 0.036 ) were independent predictors of smoking cessation . CONCLUSION We did not achieve our aim of higher smoking cessation rates in the intervention group . Future smoking cessation interventions should be more intensive , focus on patients ' social circumstances and , if possible , involve patients ' relatives . FUNDING This study was supported by the Ludvig and Sara Elsass Foundation , the Lundbeck Foundation and The Danish Heart Foundation ( Grant 07 - 4-B703-A1378 - 22384F ) . TRIAL REGISTRATION This protocol is registered with Clinical Trials.gov ( NCT 00253097 )", "Lowering blood pressure ( BP ) in stroke survivors reduces the risk of recurrent stroke . We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an intervention group compared with a control group . A total of 349 patients who had sustained acute stroke or transient ischemic attack were r and omly assigned to either usual care or to 4 home visits by a nurse . During the visits , the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle . A total of 303 patients completed the 1-year follow up . No change in systolic BP was noted in either the intervention group or the control group . Because of an increase in diastolic BP in the control group ( P = .03 ) , a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007 ) . Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group . Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P proportion of patients on antihypertensive medication increased in the intervention group ( P = .002 ) . Patients were compliant with antihypertensive therapy , and 92 % of the hypertensive patients in the intervention group followed the advice to see a general practitioner ( GP ) for BP checkups . At follow-up , 187 patients ( 62 % ) were hypertensive , with no difference in the rate of hypertension seen between the groups . Our data indicate that home visits by nurses did not result in a lowering of BP . Patients complied with antihypertensive therapy and GP visits in the case of hypertension . Nonetheless , the majority of patients were hypertensive at the 1-year follow up", "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", "BACKGROUND Adopting healthy behaviors is critical for secondary stroke prevention , but many patients fail to follow national guidelines regarding diet , exercise , and abstinence from risk factors . Compliance often decreases with time after hospital discharge , yet few studies have examined programs promoting long-term adherence to health behaviors . Goal setting and telephone follow-up have been proven to be effective in other areas of medicine , so this study evaluated the effectiveness of a guideline -based , goal - setting telephone follow-up program for patients with ischemic stroke . METHODS This was a multicenter , assessor-blinded , parallel-group , r and omized controlled trial . Ninety-one stroke patients were r and omized to either a control group or an intervention group . Intervention consisted of predischarge education and 3 goal - setting follow-up sessions conducted by phone . Data were collected at baseline and during the third and sixth months after hospital discharge . RESULTS Six months after discharge , patients in the intervention group exhibited significantly higher medication adherence than patients in the control group . There were no statistically significant differences in physical activity , nutrition , low-salt diet adherence , blood pressure monitoring , smoking abstinence , unhealthy use of alcohol , and modified Rankin Scale ( mRS ) scores between the 2 groups . CONCLUSIONS Goal - setting telephone follow-up intervention for ischemic stroke patients is feasible and leads to improved medication adherence . However , the lack of group differences in other health behavior subcategories and in themRS score indicates a need for more effective intervention strategies to help patients reach guideline -recommended targets", "BACKGROUND Reduction of blood pressure ( BP ) after stroke or TIA decreases stroke recurrence and is a major goal of secondary Stroke Prevention Clinics ( SPCs ) . Health care providers need effective screening processes to identify those clients at highest risk of not achieving BP targets and those clients at highest risk ofnon-adherence to medication . METHODS This multicentred , r and omized controlled study used a screening process to identify SPC patients with psychosocial/cognitive deficits ( e.g. , lack of confidence in the utility of medications , poor memory , mild cognitive impairment ) who were experiencing difficulty managing their BP to target values and evaluated whether a model of nurse-led case management program ( monthly telephone calls , motivational interviewingfor lifestyle change , plus home BP monitoring and use ofdosettes for medication administration ) would improve BP measures and adherence to medications . RESULTS Both intervention ( n=29 ) and usual care groups ( n=27 ) showed a trend-for'reduced BP at six months ( Median ql-q3 , Systolic BR p=0.46 ; Diastolic BR p=0.37 ) . Diabetic patients , irrespective of the group to which they were r and omized , were less likely to meet Best Practice Guideline targets than those without diabetes ( Chi Square test , p=0.0001 ) . CONCLUSION Stroke and TIA patients with diabetes may require additional re sources and support in order to reach BP target values", "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", "SIR— Interventions with an educational or counselling component have been reported to be effective in a variety of patient groups to encourage smoking cessation [ 1 ] , lower blood pressure ( BP ) [ 2 , 3 ] , achieve modest reductions in cholesterol [ 4 ] , and promote weight loss [ 5 ] . Evaluation of the impact of education on physical outcomes is lacking in stroke disease , despite evidence that inadequate provision of information may adversely affect compliance with secondary prevention and psychosocial outcomes [ 6 ] . We describe a single-blind r and omised controlled trial of health education and counselling for patients with stroke or transient ischaemic attack ( TIA ) , and its effects on risk factors , satisfaction , mood and perceived health status" ]

[ "OBJECTIVE This study evaluates the efficacy of agomelatine , the first antidepressant that is an agonist at MT(1)/MT(2 ) receptors and an antagonist at 5-HT(2C ) receptor , in the prevention of relapse of depression following successful response . METHOD Patients with DSM-IV-TR major depressive disorder who responded to an 8- or 10-week course of agomelatine 25- or 50-mg daily treatment were r and omly assigned to receive continuation treatment with agomelatine ( n=165 ) or placebo ( n=174 ) during a 24-week , r and omized , double-blind treatment period . The main outcome measure was time to relapse during the double-blind treatment period . The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis . The study was conducted from February 2005 to February 2007 . RESULTS During the 6-month evaluation period , the incidence of relapse was significantly lower in patients who continued treatment than in those switched to placebo ( P=.0001 ) . The cumulative relapse rate at 6 months for agomelatine-treated patients was 21.7 % ; that for placebo-treated patients was 46.6 % . Agomelatine was also superior to placebo in preventing relapse in the subset of patients with baseline 17-item Hamilton Depression Rating Scale total score > or = 25 . Measures of tolerability and safety of both doses of agomelatine were similar to placebo . No pattern of early relapse or adverse events suggestive of withdrawal symptoms was obtained after abrupt cessation of agomelatine . CONCLUSIONS The findings are important in 2 respects . First , agomelatine is an effective and safe antidepressant continuation therapy , which confirms efficacy seen in short-term studies . Second , few early relapses were observed in the patient group switched to placebo : the survival curve for placebo separated gradually from that of patients taking agomelatine . We suggest this reflects solely the underlying properties of the illness , which is only possible due to the lack of discontinuation syndrome after agomelatine withdrawal . It underlines the novel clinical profile of agomelatine , which quite likely reflects its innovative pharmacology . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53193024", "The anxiolytic effect of Silexan , a patented active substance with an essential oil produced from Lav and ula angustifolia flowers , was investigated in patients with anxiety-related restlessness and disturbed sleep . 170 out- patients with a diagnosis of restlessness ( ICD-10 R45.1 ) , a Hamilton Anxiety Scale ( HAMA ) total score ≥18 points and ≥2 points for HAMA items ' Tension ' and ' Insomnia ' participated in this r and omized , double-blind trial and received 80 mg Silexan or placebo once daily for 10 weeks . Patients with clinical ly important other psychiatric or neurological disorders potentially interfering with the assessment of treatment efficacy were excluded . Outcome variables were the HAMA as well as the Pittsburgh Sleep Quality Index ( PSQI ) , the Zung Self-rating Anxiety Scale , a State Check inventory and the Clinical Global Impressions question naire . In the Silexan group the HAMA total score decreased from an average of 25.5±6.0 points at baseline to 13.7±7.0 points at treatment end , compared to a decrease from 26.5±6.1 to 16.9±9.8 for placebo , corresponding to decreases of 12.0 and 9.3 points ( marginal means ) , respectively ( group difference : p=0.03 , ANCOVA with factor treatment and baseline value as covariate ) . In all outcome measures the treatment effect of Silexan was more pronounced than with placebo . According to the HAMA , 48.8 % and 33.3 % of the patients were responders ( Silexan , placebo ; reduction ≥50 % ; p=0.04 ) and 31.4 % and 22.6 % achieved remission ( HAMA ) . 33.7 % ( Silexan ) and 35.7 % ( placebo ) of the participants reported adverse events . The study confirms the calming and anxiolytic efficacy of Silexan", "Mixed anxiety and depressive disorder ( MADD ; ICD-10 F41.2 ) is a condition characterized by subsyndromal symptoms of anxiety and depression , neither of which are clearly predominant . Silexan has been demonstrated to be efficacious in subsyndromal and syndromal anxiety disorders and co-morbid depressive symptoms . In this study 318 adult out- patients with MADD according to ICD-10 criteria , a total score ≥18 points on the Hamilton Anxiety Rating Scale ( HAMA ) , and at least moderately severe anxious and depressed mood were r and omized and received 1 × 80 mg Silexan or placebo in double-blind fashion for a scheduled period of 70 days . Primary outcome measures were the HAMA and Montgomery Åsberg Depression Rating Scale ( MADRS ) total score changes between baseline and treatment end . The HAMA total score decreased by 10.8±9.6 points for Silexan and by 8.4±8.9 points for placebo ( treatment group difference : p Compared to placebo , the patients treated with Silexan had a better over-all clinical outcome and showed more pronounced improvements of impaired daily living skills and health related quality of life . Eructation was the only adverse event with a substantially higher incidence under Silexan . The study thus demonstrates that Silexan is efficacious and safe in the treatment of MADD", "Background : Although antidepressants are still a commonly used treatment for social anxiety disorder ( SAD ) , a significant proportion of patients fail to remit following antidepressants . However , no st and ard approach has been established for managing such patients . This study aim ed to examine the effectiveness of cognitive behavioral therapy ( CBT ) as an adjunct to usual care ( UC ) compared with UC alone in SAD patients who remain symptomatic following antidepressant treatment . Methods : This was a prospect i ve r and omized open-blinded end-point study with two parallel groups ( CBT + UC , and UC alone , both for 16 weeks ) conducted from June 2012 to March 2014 . SAD patients who remain symptomatic following antidepressant treatment were recruited , and a total sample size of 42 was set based on pilot results . Results : Patients were r and omly allocated to CBT + UC ( n = 21 ) or UC alone ( n = 21 ) . After 16 weeks , adjusted mean reduction in the Liebowitz Social Anxiety Scale from baseline for CBT + UC and UC alone was −40.87 and 0.68 , respectively ; the between-group difference was −41.55 ( −53.68 to −29.42 , p were 85.7 and 10.0 % for CBT + UC and UC alone , respectively ( p ) . The corresponding remission rates were 47.6 and 0.0 % , respectively ( p = 0.0005 ) . Significant differences were also found in favor of CBT + UC for social anxiety symptoms , depressive symptoms , and functional impairment . Conclusions : Our results suggest that in SAD patients who have been ineffectively treated with antidepressants , CBT is an effective treatment adjunct to UC over 16 weeks in reducing social anxiety and related symptoms", "Background : Agomelatine is a novel agent that acts on melatonergic ( MT1 , MT2 ) receptors and serotonergic ( 5-HT2C ) receptors . Pre clinical data and data from clinical trials in major depression suggest that agomelatine may have anxiolytic properties . A r and omized , double-blind , placebo-controlled trial was design ed to assess the efficacy of agomelatine in generalized anxiety disorder ( GAD ) . Methods : One hundred twenty-one patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition GAD and no comorbid disorders were r and omized to agomelatine ( 25 - 50 mg/d ) or placebo for 12 weeks . The primary outcome measure was the Hamilton Anxiety Rating Scale , whereas secondary outcome measures included the Clinical Global Impression scales , the Leeds Sleep Evaluation Question naire , and the Sheehan Disability Scale . Safety measures included assessment of spontaneously reported adverse events , laboratory monitoring , and the Discontinuation Emergent Signs and Symptoms Scale to evaluate discontinuation symptoms . Results : Analysis of covariance of change in the last Hamilton Anxiety Rating Scale total score from baseline demonstrated significant superiority of agomelatine 25 to 50 mg as compared with placebo ( E [ SE ] = −3.28 [ 1.58 ] ; 95 % confidence interval = −6.41 to −0.15 ; P = 0.040 ) . Data on secondary outcome measures , including clinical response , symptoms of insomnia , and improvement in associated disability , were consistent with the efficacy of agomelatine . Safety analysis indicated that agomelatine was tolerated as well as placebo and was devoid of discontinuation emergent symptoms . Conclusions : This study suggests that agomelatine is effective in the treatment of GAD and is well tolerated . Additional trials , using an active comparator and extending over a longer period , are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for anxiety disorders", "The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) as maintenance monotherapy for patients with generalized anxiety disorder ( GAD ) . Time-to-event ( anxiety symptom recurrence ; maximum 52 weeks ) multicenter , r and omized-withdrawal , parallel-group , double-blind , placebo-controlled study of quetiapine XR ( 50–300 mg/day ) following open-label run-in ( 4–8 weeks ) and open-label stabilization ( ≥12 weeks ) . Primary variable : time from r and omization to anxiety event . Secondary variables included : Hamilton Anxiety Rating Scale ( HAM-A ) total , HAM-A psychic/somatic anxiety factors , Clinical Global Impression-Severity of Illness ( CGI-S ) , and Quality of Life , Enjoyment and Satisfaction Question naire ( Q-LES-Q ) scores ; adverse events ( AE ) reporting . Four hundred and thirty-two patients , stabilized on quetiapine XR , were r and omized to continue quetiapine XR ( N=216 ) or switch to placebo ( N=216 ) . Risk of anxiety symptom recurrence was significantly reduced by 81 % for quetiapine XR versus placebo : hazard ratio=0.19 ( 95 % confidence interval 0.12–0.31 ; P receiving quetiapine XR ( N=22 , 10.2 % ) than placebo ( N=84 , 38.9 % ) experienced anxiety symptom recurrence . Significant differences were observed between quetiapine XR and placebo in : HAM-A total , psychic/somatic , CGI-S ( all P Q-LES-Q ( P 10 % ) during open-label treatment were dry mouth , sedation , somnolence , dizziness , fatigue , and constipation . During r and omized treatment , the most common AEs for quetiapine XR were headache and nasopharyngitis . Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR , with tolerability results consistent with the known profile of quetiapine ", "The efficacy and tolerability of extended-release quetiapine fumarate ( quetiapine XR ) once-daily monotherapy in generalized anxiety disorder ( GAD ) was assessed . This multicentre , double-blind , r and omized , placebo- and active-controlled , phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk ( 8-wk active treatment , 2-wk post-treatment drug-discontinuation ) study period ; 873 patients were r and omized to 50 mg or 150 mg quetiapine XR , 20 mg paroxetine , or placebo . Primary endpoint was change from r and omization at week 8 in Hamilton Rating Scale for Anxiety ( HAMA ) total score . At week 8 , all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo ; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR . Significant separation from placebo ( -2.90 ) in HAMA total score was observed at day 4 for 50 mg quetiapine XR ( -4.43 , p quetiapine XR ( -3.86 , p paroxetine ( -2.69 ) . Remission ( HAMA total score 7 ) rates at week 8 were significantly higher for 150 mg quetiapine XR ( 42.6 % , p paroxetine ( 38.8 % , p adverse events ( AEs ) were dry mouth , somnolence , fatigue , dizziness , and headache , for quetiapine XR , and nausea , headache , dizziness for paroxetine . A lower proportion of patients reported sexual dysfunction with quetiapine XR [ 0.9 % ( 50 mg ) , 1.8 % ( 150 mg ) ] than with placebo ( 2.3 % ) or paroxetine ( 7.4 % ) . The incidence of AEs potentially related to extrapyramidal symptoms was : quetiapine XR : 50 mg , 6.8 % , 150 mg , 5.0 % ; placebo , 1.8 % ; and paroxetine , 8.4 % . Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD , with symptom improvement seen as early as day 4", "BACKGROUND There is debate about combining benzodiazepines with selective serotonin reuptake inhibitors in the acute treatment of panic disorder . Although this medication combination is widely used in clinical practice , there is no well-tested , optimal method of coadministering these medications for the treatment of panic disorder . The purpose of this study was to test the efficacy of early coadministration of clonazepam with sertraline in the treatment of panic disorder . METHODS Fifty patients with panic disorder were r and omized into a double-blind clinical trial . Patients received open-label sertraline for 12 weeks ( target dose , 100 mg/d ) , and in addition were r and omized to groups receiving either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the first 4 weeks of the trial . The clonazepam dose was then tapered during 3 weeks and discontinued . RESULTS Thirty-four ( 68 % ) of 50 patients completed the trial . Drop-out rates were similar in the sertraline/placebo vs the sertraline/clonazepam group ( 38 % vs 25 % ) ( P = .5 ) . An intent-to-treat analysis ( on last observation carried forward data ) revealed a much greater proportion of responders in the sertraline/clonazepam compared with the sertraline/placebo group at the end of week 1 of the trial ( 41 % vs 4 % ) ( P = .003 ) . There was also a significant between-group difference at the end of week 3 with 14 ( 63 % ) of 22 of the sertraline/clonazepam group responding to treatment vs 8 ( 32 % ) of 25 of the sertraline/placebo group ( P = .05 ) . This difference was not observed at other times during the trial . CONCLUSION These data indicate that rapid stabilization of panic symptoms can be safely achieved with a sertraline/clonazepam combination , supporting the clinical utility of this type of regimen for facilitating early improvement of panic symptoms relative to sertraline alone", "Background Generalized anxiety disorder ( GAD ) is generally considered to be a chronic condition , waxing and waning in severity ; however prospect i ve investigation of the course of GAD in community sample s is lacking . This study seeks to fill that gap , by identifying the whole spectrum of generalized anxiety syndromes , sub-typing them according to their duration and frequency of occurrence , and evaluating their long-term course and outcome in the community . Method The prospect i ve Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults ( N = 591 ) ( aged 20 years at first interview ) by six interviews over a period of 20 years ( 1979–1999 ) . GAD syndromes were defined by DSM-III symptom criteria without applying any exclusion criteria . A spectrum of generalized anxiety was defined by duration : 6 months ( DSM-IV ) , 1 month ( DSM-III ) , ≤2 weeks ( with weekly occurrence over one year ) , and anxiety symptoms . From 1978 ( screening ) to 1999 the annual presence of symptoms and treatment was assessed . Persistence of anxiety was defined by the almost daily presence of symptoms over the previous 12 months . Results The annual incidence of DSM-III GAD increased considerably between the ages of 20 and 40 . The average age of onset of symptoms was 15.6 years ; in 75 % of cases it occurred before the age of 20 . 75 of 105 DSM-III GAD cases had at least one follow-up . At their individual last follow-up , 12 of those 75 subjects ( 16 % ) were re-diagnosed as having GAD , 22 ( 29 % ) manifested subthreshold syndromes or anxiety symptoms , while 39 cases , the majority , ( 52 % ) were symptom-free ; 5 of the 12 re-diagnosed GAD cases were persistent ( corresponding to 7 % of all 75 initial GAD cases ) . In their twenties they were treated at some time in 6 % of all years , but in their thirties this figure rose to 12 % . At their individual last follow-up 26 % of 6-month GAD subjects and 22 % of 1-month GAD subjects were still being treated . Treated vs. non-treated subjects did not differ in terms of gender but did differ in severity , persistence and in comorbidity with bipolar-II disorder , social phobia , obsessive-compulsive syndromes and substance-use disorders . Limitations Results are based on a relatively small sample and can not be generalized to adults aged over 40 years . Conclusions The course of DSM-III-defined GAD may not be chronic , as previously suggested , but mainly recurrent with intervening symptom-free periods of recovery in about half of cases . Over a period of 20 years there was more improvement than progression within the anxiety spectrum", "OBJECTIVE To evaluate the feasibility , acceptability , and preliminary efficacy of a novel behavioral intervention for reducing symptoms of selective mutism and increasing functional speech . METHOD A total of 21 children ages 4 to 8 with primary selective mutism were r and omized to 24 weeks of Integrated Behavior Therapy for Selective Mutism ( IBTSM ) or a 12-week Waitlist control . Clinical outcomes were assessed using blind independent evaluators , parent- , and teacher-report , and an objective behavioral measure . Treatment recipients completed a three-month follow-up to assess durability of treatment gains . RESULTS Data indicated increased functional speaking behavior post-treatment as rated by parents and teachers , with a high rate of treatment responders as rated by blind independent evaluators ( 75 % ) . Conversely , children in the Waitlist comparison group did not experience significant improvements in speaking behaviors . Children who received IBTSM also demonstrated significant improvements in number of words spoken at school compared to baseline , however , significant group differences did not emerge . Treatment recipients also experienced significant reductions in social anxiety per parent , but not teacher , report . Clinical gains were maintained over 3 month follow-up . CONCLUSION IBTSM appears to be a promising new intervention that is efficacious in increasing functional speaking behaviors , feasible , and acceptable to parents and teachers", "Abstract Objective . Anxiety disorders are frequently under-diagnosed conditions in primary care , although they can be managed effectively by general practitioners . Methods . This paper is a short and practical summary of the World Federation of Biological Psychiatry ( WFSBP ) guidelines for the pharmacological treatment of anxiety disorders , obsessive – compulsive disorder ( OCD ) and posttraumatic stress disorder ( PTSD ) for the treatment in primary care . The recommendations were developed by a task force of 30 international experts in the field and are based on r and omized controlled studies . Results . First-line pharmacological treatments for these disorders are selective serotonin reuptake inhibitors ( for all disorders ) , serotonin-norepinephrine reuptake inhibitors ( for some ) and pregabalin ( for generalized anxiety disorder only ) . A combination of medication and cognitive behavior/exposure therapy was shown to be a clinical ly desired treatment strategy . Conclusions . This short version of an evidence -based guideline may improve treatment of anxiety disorders , OCD , and PTSD in primary care", "A previous review summarized what was then known about the potential role of pregabalin in the treatment of patients with generalized anxiety disorder ( GAD ) : this review provides an up date on its pharmacological properties and presumed mechanism of action , the liability for abuse , and efficacy and tolerability in patients with GAD . Pregabalin has a similar molecular structure to the inhibitory neurotransmitter gamma amino butyric acid ( GABA ) but its mechanism of action does not appear to be mediated through effects on GABA . Instead , its anxiolytic effects may arise through high-affinity binding to the alpha-2-delta sub-unit of the P/Q type voltage-gated calcium channel in “ over-excited ” presynaptic neurons , thereby reducing the release of excitatory neurotransmitters such as glutamate . The findings of r and omized controlled trials and meta-analyses together indicate that pregabalin is efficacious in both acute treatment and relapse prevention in GAD , with some evidence of an early onset of effect , and broad efficacy in reducing the severity of psychological and physical symptoms of anxiety . It also has efficacy as an augmenting agent after non-response to antidepressant treatment in GAD . Continuing vigilance is needed in assessing its potential abuse liability but the tolerability profile of pregabalin may confer some advantages over other pharmacological treatments in the short term for treatment in patients with GAD", "Although St John 's wort ( Hypericum perforatum ) is one of the most widely used and studied herbal medicines for depression , less is known about its efficacy in anxiety disorders , in spite of the fact that patients with anxiety disorders are among the most likely to self-medicate using alternative treatments . Pharmacokinetic evidence for the serotonergic , domaminergic and GABAminergic activity of hypericum , and a recent successful open-label study , suggests that it may be effective for obsessive – compulsive disorder ( OCD ) . Sixty subjects were r and omized to 12 weeks of treatment with St John 's wort ( LI 160 ) or matching placebo . Subjects with Hamilton Depression Scale scores of 16 or above were excluded . A flexible-dose schedule was utilized ( 600–1800 mg/day ) . The mean change on the Yale – Brown Obsessive – Compulsive Scale ( Y-BOCS ) with St John 's wort ( 3.43 ) was not significantly different than the mean change found with placebo ( 3.60 ) ( P=899 ) . No significant differences were found on any of the Y-BOCS subscales . The percentage of patients rated as ‘ much ’ or ‘ very much ’ improved at endpoint was not significantly different between St John 's wort ( 17.9 % ) and placebo ( 16.7 % ) ( P=0.905 ) . Only one patient from each group discontinued due to adverse events [ sinus infection ( St John 's wort ) ; confusion ( placebo ) ] . The results fail to support the efficacy of St John 's wort for OCD", "BACKGROUND Paroxetine has demonstrated efficacy in depression and anxiety disorders , including generalized anxiety disorder ( GAD ) . This 32-week study evaluated the maintained efficacy and safety of paroxetine in GAD by assessing the potential for relapse after discontinuation of medication . METHOD Adults ( N = 652 ) with DSM-IV GAD and a Clinical Global Impressions-Severity of Illness ( CGI-S ) score > or = 4 received paroxetine ( 20 - 50 mg/day ) for 8 weeks . Patients whose CGI-S score had decreased by at least 2 points to r and omly assigned to double-blind treatment with paroxetine ( N = 278 ) or placebo ( N = 288 ) for a further 24 weeks . The primary efficacy parameter was the proportion of patients relapsing ( an increase in CGI-S score of at least 2 points to a score efficacy ) during double-blind treatment . RESULTS Significantly fewer paroxetine than placebo patients relapsed during the 24-week double-blind phase ( 10.9 % vs. 39.9 % ; p Placebo patients were almost 5 times more likely to relapse than paroxetine patients ( estimated hazard ratio = 0.213 [ 95 % CI = 0.1 to 0.3 ] ; p secondary efficacy parameters , including functional status . Twice as many paroxetine patients as placebo patients ( 73 % ) achieved remission . Paroxetine was well tolerated , with no unexpected adverse events reported . CONCLUSION Paroxetine was found to be effective and well tolerated for both the short- and long-term treatment of DSM-IV GAD . Continued treatment with paroxetine significantly reduced the potential for relapse of GAD symptoms", "In this study , we evaluated the efficacy and safety of kava kava ( Piper methysticum ) in generalized anxiety disorder . Data were analyzed from three r and omized , double-blind , placebo-controlled trials of kava , including one study with an active comparator ( venlafaxine ) , in adult out patients with DSM-IV generalized anxiety disorder . The pooled sample ( n=64 ) included the following number of participants : kava , n=28 ; placebo , n=30 ; and venlafaxine , n=6 . Given the comparability of the study design s , the data comparing kava and placebo were then pooled for further efficacy and safety analyses . No significant differences were observed between the treatment groups in any of the trials . In the pooled analyses , no effects were found for kava , while a significant effect in favor of placebo was observed in participants with higher anxiety at baseline . No evidence of hepatotoxicity was found with kava , and all of the treatments were well tolerated . Findings from these three controlled trials do not support the use of kava in DSM-IV generalized anxiety disorder", "After initial interviews with 20,291 adults in the National Institute of Mental Health Epidemiologic Catchment Area Program , we estimated prospect i ve 1-year prevalence and service use rates of mental and addictive disorders in the US population . An annual prevalence rate of 28.1 % was found for these disorders , composed of a 1-month point prevalence of 15.7 % ( at wave 1 ) and a 1-year incidence of new or recurrent disorders identified in 12.3 % of the population at wave 2 . During the 1-year follow-up period , 6.6 % of the total sample developed one or more new disorders after being assessed as having no previous lifetime diagnosis at wave 1 . An additional 5.7 % of the population , with a history of some previous disorder at wave 1 , had an acute relapse or suffered from a new disorder in 1 year . Irrespective of diagnosis , 14.7 % of the US population in 1 year reported use of services in one or more component sectors of the de facto US mental and addictive service system . With some overlap between sectors , specialists in mental and addictive disorders provided treatment to 5.9 % of the US population , 6.4 % sought such services from general medical physicians , 3.0 % sought these services from other human service professionals , and 4.1 % turned to the voluntary support sector for such care . Of those persons with any disorder , only 28.5 % ( 8.0 per 100 population ) sought mental health/addictive services . Persons with specific disorders varied in the proportion who used services , from a high of more than 60 % for somatization , schizophrenia , and bipolar disorders to a low of less than 25 % for addictive disorders and severe cognitive impairment . Applications of these descriptive data to US health care system reform options are considered in the context of other variables that will determine national health policy", "OBJECTIVE The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo . METHOD Forty-six out patients suffering from moderate to severe panic disorder with or without agoraphobia ( DSM-III-R criteria ) were r and omly assigned to a 10-week treatment protocol of regular aerobic exercise ( running ) , clomipramine ( 112.5 mg/day ) , or placebo pills . RESULTS The dropout rate was 31 % for the exercise group , 27 % for the placebo group , and 0 % for the clomipramine group . In comparison with placebo , both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures ( analysis of variance , last-observation-carried-forward method and completer analysis ) . A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively . Depressive symptoms were also significantly improved by exercise and clomipramine treatment . CONCLUSIONS These results suggest that regular aerobic exercise alone , in comparison with placebo , is associated with significant clinical improvement in patients suffering from panic disorder , but that it is less effective than treatment with clomipramine", "BACKGROUND The efficacy of selective serotonin reuptake inhibitors in the acute treatment of social anxiety disorder ( social phobia ) is well established . OBJECTIVE To evaluate whether the efficacy of paroxetine hydrochloride in this disorder is maintained in the long term . METHODS This was a placebo-controlled multicenter study comprising a single-blind acute treatment phase ( 12 weeks ) and a r and omized , double-blind maintenance treatment phase ( 24 weeks ) for patients who had responded to paroxetine during the acute phase . Four hundred thirty-seven adult patients with social anxiety disorder ( according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria , code 300.23 ) entered the acute phase , and 323 continued into the maintenance phase ( 162 paroxetine and 161 placebo ) . The principal outcome measure was the proportion of patients relapsing during the maintenance phase . RESULTS Two hundred fifty-seven patients completed the study ( 136 paroxetine-treated and 121 placebo-treated patients ) . Significantly fewer patients relapsed in the paroxetine group than in the placebo group ( 14 % vs 39 % ; odds ratio , 0.24 ; 95 % confidence interval , 0.14 - 0.43 ; P paroxetine group showed improvement as shown on the Clinical Global Impression global improvement rating compared with the placebo group ( 78 % vs 51 % ; odds ratio , 3.66 ; 95 % confidence interval , 2.22 - 6.04 ; P placebo , paroxetine treatment significantly ( P symptoms of social anxiety as shown on the Liebowitz Social Anxiety Scale , Social Phobia Inventory , Sheehan Disability Scale , Symptom Checklist-90 score , and EuroQol visual analogue scale , indicating decreased disability and increased well-being . Paroxetine was well tolerated . CONCLUSION Paroxetine is an effective long-term treatment for social anxiety disorder", "BACKGROUND Agomelatine was efficacious in reducing symptoms in a short-term placebo-controlled trial in generalized anxiety disorder ( GAD ) and in preventing relapse in a longer term placebo-controlled study . An additional short-term placebo-controlled study is required by regulatory agencies to confirm the efficacy of agomelatine in GAD . METHOD This 12-week , placebo-controlled , double-blind , r and omized , parallel group , international , multicenter study was design ed to confirm the efficacy of agomelatine 25 - 50 mg/d in the treatment of patients with a primary DSM-IV-TR diagnosis of GAD . The primary outcome measure was the Hamilton Anxiety Rating Scale ( HARS ) total score . Assay sensitivity was evaluated by including an escitalopram ( 10 - 20 mg/d ) group . SETTING S The study was undertaken in 45 clinical centers in Argentina , Czech Republic , Finl and , South Korea , Pol and , Russia , and Slovakia from April 2010 to July 2011 . RESULTS One hundred thirty-nine out patients were included in the agomelatine group , 131 in the placebo group , and 142 in the escitalopram group . Agomelatine significantly reduced mean ( SD ) HARS total score ( agomelatine-placebo difference : 4.71 [ 1.03 ] , P including psychic and somatic HARS subscales , response rate ( estimate [ st and ard error ] ) ( agomelatine-placebo difference : 27.4 % [ 5.9 % ] , P .0001 ) , remission on the HARS ( agomelatine-placebo difference : 16.8 % [ 5.4 % ] , P = .002 ) , Clinical Global Impressions-Severity of Illness scale ( CGI-S ) ( P .001 ) , functional impairment ( P .0001 ) , and sleep quality ( P more severely ill patients ( HARS total score ≥ 25 with or without CGI-S ≥ 5 at baseline ) . Agomelatine was well tolerated by patients , with no more adverse events than placebo . Escitalopram was similarly efficacious but was accompanied by a higher incidence of adverse events compared to placebo . CONCLUSIONS In clinical practice , agomelatine has at least similar efficacy to that of escitalopram for the short-term treatment of GAD and is well tolerated . TRIAL REGISTRATION Controlled-Trials.com identifier : IS RCT N03554974", "OBJECTIVE The primary disadvantage of high-potency benzodiazepine treatment for panic disorder is the difficulty of discontinuing the treatment . During treatment discontinuation , new symptoms may emerge and anxiety may return , preventing many patients from successfully discontinuing their treatment . In this controlled , r and omized trial the authors investigated the efficacy of a cognitive-behavioral program for patients with panic disorder who were attempting to discontinue treatment with high-potency benzodiazepines . METHOD Out patients treated for panic disorder with alprazolam or clonazepam for a minimum of 6 months and expressing a desire to stop taking the medication ( N = 33 ) were r and omly assigned to one of two taper conditions : a slow taper condition alone or a slow taper condition in conjunction with 10 weeks of group cognitive-behavioral therapy . RESULTS The rate of successful discontinuation of benzodiazepine treatment was significantly higher for the patients receiving the cognitive-behavioral program ( 13 of 17 ; 76 % ) than for the patients receiving the slow taper program alone ( four of 16 ; 25 % ) . There was no difference in the likelihood of discontinuation success between the patients treated with alprazolam and those who received clonazepam . At the 3-month follow-up evaluation , 77 % of the patients in the cognitive-behavioral program who successfully discontinued benzodiazepine treatment remained benzodiazepine free . CONCLUSIONS These findings support the efficacy of cognitive-behavioral interventions in aiding benzodiazepine discontinuation for patients with panic disorder", "BACKGROUND A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia , the Panic and Agoraphobia Scale ( P & A ) . The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients ( panic attacks , avoidance , anticipatory anxiety , disability and worries about health ) . The application of this scale in a double-blind placebo-controlled panic disorder trial is described . At the same time , the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy . METHODS Patients with Panic disorder ( DSM-IV ) were r and omly assigned to three treatment modalities : running ( n=45 ) , clomipramine ( n=15 ) or placebo ( n=15 ) . Treatment efficacy was measured with the Panic and Agoraphobia Scale ( P & A ) and other rating scales . RESULTS According to the P & A and other scales , both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment . Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise . The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability . CONCLUSIONS The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments . Analysis of the scales five subscores may help to underst and mechanisms of action of panic disorder treatments", "This study evaluated once-daily , extended-release quetiapine fumarate ( quetiapine XR ) monotherapy in generalized anxiety disorder ( GAD ) . This was a 10-week ( 8-week active treatment/2-week posttreatment drug-discontinuation/tapering phase ) , double-blind , r and omized , placebo-controlled study ( D1448C00009 ) . Primary end point was change from r and omization at week 8 in Hamilton Anxiety Rating Scale ( HAM-A ) total score . Overall , 951 patients with GAD were r and omized ( quetiapine XR : 50 mg/d , n = 234 ; 150 mg/d , n = 241 ; 300 mg/d , n = 241 ; placebo , n = 235 ) . At week 8 , HAM-A total scores significantly ( P with quetiapine XR 50 mg/d ( −13.31 ) and 150 mg/d ( −13.54 ) , but not 300 mg/d ( −11.87 ; P = 0.240 ) . At week 1 , HAM-A total scores significantly improved versus placebo ( −5.94 ) with quetiapine XR 50 mg/d ( −7.47 ; P Versus placebo at week 8 , quetiapine XR 50 and 150 mg/d significantly improved HAM-A psychic ( P 0.001 , respectively ) and somatic ( P 0.01 , respectively ) cluster scores , HAM-A response ( ≥50 % total score reduction ; P , and Clinical Global Impression-Improvement categorical changes ( P For quetiapine XR 150 mg/d , significant ( P seen for HAM-A remission ( total score , ≤7 ) and Clinical Global Impression-Severity of Illness scores . For quetiapine XR 300 mg/d , improvements in these secondary variables were not significantly different versus placebo . Pittsburgh Sleep Quality Index global scores improved with all 3 doses ( quetiapine : XR 50 mg/d , −4.07 [ P . Adverse events ( > 10 % with quetiapine XR ) were dry mouth , somnolence , sedation , dizziness , headache , and fatigue . Quetiapine XR ( 50/150 mg/d ) monotherapy was effective at week 8 in patients with GAD ; symptom improvement was seen at week 1 for all doses ( 50/150/300 mg/d ) . Safety and tolerability were consistent with the known profile of quetiapine", "The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates . Thirty-six out patients with generalized anxiety disorder ( DSM III-R ) , after a 2-week wash-out , were r and omized to one of the following three treatments for 4 weeks ( n = 12 per group ) : valepotriates ( mean daily dose : 81.3 mg ) , diazepam ( mean daily dose : 6.5 mg ) , or placebo . A parallel , double-blind , flexible-dose , placebo-controlled design was employed . No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale ( HAM-A ) or in the trait part of the state-trait anxiety inventory ( STAI-trait ) . Moreover , the three groups presented a significant reduction in the total HAM-A scores . On the other h and , only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait . Although the principal analysis ( HAM-A between group comparison ) found negative results ( probably due to the small sample size in each group ) , the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety . However , since the number of subjects per group was very small , the present results must be viewed as preliminary . Thus , further studies addressing this issue are warranted", "OBJECTIVE This study evaluated the efficacy and tolerability of agomelatine in the prevention of relapse in patients with generalized anxiety disorder ( GAD ) . METHOD Patients with GAD ( Hamilton Anxiety Rating Scale [ HARS ] ≥ 22 , with items 1 and 2 ≥ 2 , item 1 + 2 ≥ 5 ; Montgomery-Asberg Depression Rating Scale [ MADRS ] ≤ 16 ; and HARS total score between screening and baseline ) who responded to a 16-week course of agomelatine 25 - 50 mg/d treatment were r and omly assigned to receive continuation treatment with agomelatine ( n = 113 ) or placebo ( n = 114 ) for 26 weeks . The main outcome measure was time to relapse during this maintenance period . The estimated risk of relapse was calculated using the Kaplan-Meier method , and groups were compared using a log-rank test stratified for country . The study was undertaken in 31 clinical centers in Canada , Denmark , Estonia , Finl and , Hungary , and Sweden from November 2007 to September 2009 . RESULTS During the 6-month maintenance period , the proportion of patients that relapsed during the double-blind period in the agomelatine group ( 22 patients , 19.5 % ) was lower than in the placebo group ( 35 patients , 30.7 % ) . The risk of relapse over time was significantly lower for patients who continued treatment than for those switched to placebo ( P = .046 , log-rank test stratified for country ) . Agomelatine was also superior to placebo in preventing relapse in the subset of more severe patients with baseline HARS total score ≥ 25 and CGI-S score ≥ 5 . The tolerability of agomelatine was good throughout the study , and there were no differences in discontinuation symptoms after withdrawal of agomelatine in comparison to maintenance on agomelatine . CONCLUSIONS The present study extends the positive findings of an earlier short-term study of agomelatine in GAD , demonstrating that agomelatine is effective and well-tolerated in the longer-term treatment of this chronic disorder . TRIAL REGISTRATION www.is rct n.org identifier : IS RCT N38094599", "Abstract Objectives . Regular aerobic exercise ( running ) has been shown to be superior to a pill placebo in the treatment of panic disorder . Combined drug and exercise treatment has not been investigated in r and omized controlled studies to date . Methods . This is a r and omized , 10-week , controlled , parallel group , pilot study . A total of 75 out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 ) received either ( 1 ) exercise plus paroxetine 40 mg/day ( n=21 ) , ( 2 ) relaxation plus paroxetine ( n=17 ) , ( 3 ) exercise plus pill placebo ( n=20 ) , or ( 4 ) relaxation plus pill placebo ( n=17 ) . Changes in the Panic and Agoraphobia Scale ( P&A ) , and the Clinical Global Impression Scale ( CGI ) underwent repeated measure analysis . Results . Effects sizes were large for all groups ( d=1.53–3.87 ) , however not significantly different . Paroxetine-treated patients were significantly more improved than placebo-treated patients . On the CGI , patients in the exercise groups ( plus paroxetine or placebo ) had a trend toward better improvement compared to relaxation ( P=0.06 ) . Response and remission rates were higher in the paroxetine compared to pill placebo groups . Conclusions . While paroxetine was superior to placebo , aerobic exercise did not differ from relaxation training in most efficacy measures", "Abstract : The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia , respectively . There is limited evidence to support their effectiveness for these common symptoms . The Internet has been used to a limited extent for research , but it is not known whether r and omized controlled trials can be conducted entirely using Internet technology . We performed a r and omized , double-blind , placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality . E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants ( 1551 ) from 45 states over an 8-week period . Participants were first asked to read study information , complete an online informed consent process , and undergo electronic identity verification . In order to be eligible for the study , participants were required to have 1 ) anxiety as documented by scores of at least 0.5 st and ard deviations above the mean on the State-Trait Anxiety Inventory State subtest ( STAI-State ) on 2 separate occasions , and 2 ) insomnia , defined as a \" problem getting to sleep or staying asleep over the past 2 weeks . \" We r and omly assigned 391 eligible participants to 1 of the following 3 groups , and mailed 28 days ' supply : kava with valerian placebo ( n = 121 ) , valerian with kava placebo ( n = 135 ) , or double placebo ( n = 135 ) . The primary outcome measures were changes from baseline in anxiety ( STAI-State question naire ) and insomnia ( Insomnia Severity Index [ ISI ] ) compared with placebo . Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI . Those receiving kava had similar reductions in STAI-State score ( 2.7 point greater reduction in placebo compared with kava ; 95 % confidence interval [ CI ] , −0.8 to + 6.2 ) . Those receiving valerian and placebo had similar improvements in sleep ( 0.4 point greater reduction in the placebo than the valerian group ; 95 % CI , −1.3 to + 2.1 ) . Results were similar when limited to the 83 % of participants who adhered to study compounds for all 4 weeks . Neither kava nor valerian relieved anxiety or insomnia more than placebo . This trial demonstrates the feasibility of conducting r and omized , blinded trials entirely via the Internet . Abbreviations : ISI = Insomnia Severity Index , STAI = State-Trait Anxiety Inventory ", "Opinion statementThe last decade has seen considerable advances in the treatment of anxiety disorders in children and adolescents and a considerable expansion of the evidence base for psychopharmacologic interventions in this population . The extant data suggest that , for fear-based anxiety disorders ( e.g. , generalized anxiety disorder , social phobia/social anxiety disorder , and separation anxiety disorder ) , selective serotonin reuptake inhibitors ( SSRIs ) , and selective serotonin norepinephrine reuptake inhibitors ( SSNRIs ) are well tolerated and offer considerable benefit . However , the salutary effects of SSRIs and SSNRIs in pediatric anxiety disorders are consistently amplified by the addition of psychotherapy , particularly in individuals with social anxiety disorder . Additionally , several key demographic and clinical factors , including male sex , non-minority status , and better family functioning and younger age predict greater symptomatic improvement in youth with fear-based anxiety disorders . Thus , current data suggest that in addition to several forms of psychotherapy , including cognitive-behavioral therapy ( CBT ) , SSRIs , and SSNRIs are efficacious in the treatment of these conditions in youth and that CBT + an SSRI may be associated with greater improvement than would be expected with either treatment as monotherapy . Finally , given that some children and adolescents may exhibit partial response to current pharmacotherapies , benzodiazepines , anti-histamines , and other agents may have adjunctive roles , despite a lack of data in terms of large , r and omized controlled trials", "The objective was to examine duloxetine 60 - 120 mg/day treatment for relapse prevention in adults with generalized anxiety disorder ( GAD ) . Adult patients ( N=887 ; mean age=43.3 years ; 61.0 % female ) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks . Patients who completed open-label phase and were treatment responders ( > or=50 % reduction in Hamilton Anxiety Rating Scale total score to duloxetine or placebo for a 26-week double-blind continuation phase . Relapse was defined as > or=2-point increase in illness severity ratings or by discontinuation due to lack of efficacy . During the double-blind phase , placebo-treated patients ( N=201 ) relapsed more frequently ( 41.8 % ) than duloxetine-treated patients ( 13.7 % , N=204 , P outcome measure ( P Duloxetine 60 - 120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD", "We compared the effect on withdrawal severity and acute outcome of a 25 % per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients . Patients unable to tolerate taper were permitted to slow the taper rate . Ninety percent of patients experienced a withdrawal reaction , but it was rarely more than mild to moderate . Nonetheless , 32 % of long half-life and 42 % of short half-life benzodiazepine-treated patients were unable to achieve a drug-free state . The most difficulty was experienced in the last half of taper . Baseline personality , high Eysenck neuroticism , female sex , and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life . These findings suggest that personality factors contribute significantly to the patient 's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines", "In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines", "BACKGROUND Anxiety disorders are common psychiatric conditions affecting children and adolescents . Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders , little is known about their relative or combined efficacy . METHODS In this r and omized , controlled trial , we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder , generalized anxiety disorder , or social phobia to receive 14 sessions of cognitive behavioral therapy , sertraline ( at a dose of up to 200 mg per day ) , a combination of sertraline and cognitive behavioral therapy , or a placebo drug for 12 weeks in a 2:2:2:1 ratio . We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4 , 8 , and 12 . RESULTS The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7 % for combination therapy ( P cognitive behavioral therapy ( P sertraline ( P placebo ( 23.7 % ) . Combination therapy was superior to both monotherapies ( P Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response ; combination therapy had a greater response than cognitive behavioral therapy , which was equivalent to sertraline , and all therapies were superior to placebo . Adverse events , including suicidal and homicidal ideation , were no more frequent in the sertraline group than in the placebo group . No child attempted suicide . There was less insomnia , fatigue , sedation , and restlessness associated with cognitive behavioral therapy than with sertraline . CONCLUSIONS Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders ; a combination of the two therapies had a superior response rate . ( Clinical Trials.gov number , NCT00052078 .", "OBJECTIVE Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder ( SAD ) . The present relapse prevention study investigated relapse rates during a 24-week , r and omized , double-blind , placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with escitalopram . METHOD A total of 517 patients with a primary diagnosis of generalized SAD ( per DSM-IV criteria ) and a Liebowitz Social Anxiety Scale ( LSAS ) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses ( 10 - 20 mg/day ) of escitalopram . Of these patients , 371 responded ( Clinical Global Impressions-Improvement scale [ CGI-I ] score of 1 or 2 ) and were r and omly assigned to 24 weeks of double-blind treatment with escitalo-pram ( 10 or 20 mg/day ) ( N = 190 ) or placebo ( N = 181 ) , continuing with the dose level administered at the end of the open-label period . Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy , as judged by the investigator . The study was conducted from January 2001 to June 2002 . RESULTS Survival analysis of relapse and time to relapse showed a significant advantage for escitalopram compared to placebo ( log-rank test : p risk of relapse was 2.8 times higher for placebo-treated patients than for escitalopram-treated patients ( p escitalopram-treated patients relapsing ( 22 % vs. 50 % ) , at both doses . Escitalopram was well tolerated during double-blind treatment of generalized SAD , and only 2.6 % of the escitalopram-treated patients withdrew because of adverse events . The overall discontinuation rate , excluding relapses , was 13.2 % for patients treated with escitalopram and 8.3 % for patients treated with placebo . CONCLUSION Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD", "The effects of an abrupt interruption of agomelatine , a new melatonergic/serotonergic antidepressant , were explored in a double-blind , placebo-controlled study . Paroxetine was used as active control . After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day , sustained remitted depressed patients were r and omized for 2 weeks , under double-blind conditions , to placebo or to their initial antidepressant treatment . Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the Discontinuation Emergent Signs and Symptoms ( DESS ) checklist . One hundred and ninety-two sustained remitted patients were r and omized to the 2-week discontinuation period . Patients who discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine . Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms , during the first week , compared to those who continued with paroxetine ( respective mean number of emergent symptoms : 7.3±7.1 and 3.5±4.1 , P to paroxetine , abrupt cessation of agomelatine is not associated with discontinuation symptoms ", "BACKGROUND R and omized controlled psychosocial treatment studies on selective mutism ( SM ) are lacking . METHOD Overall , 24 children with SM , aged 3 - 9 years , were r and omized to 3 months treatment ( n = 12 ) or wait list ( n = 12 ) . Primary outcome measure was the School Speech Question naire . RESULTS A significant time by group interaction was found ( p = .029 ) with significantly increased speech in the treatment group ( p = .004 ) and no change in wait list controls ( p = .936 ) . A time by age interaction favoured younger children ( p = .029 ) . Clinical trail registration : Norwegian Research CouncilNCT01002196 . CONCLUSIONS The treatment significantly improved speech . Greater improvement in the younger age group highlights the importance of an early intervention", "The anxiolytic efficacy of the orally administered lavender oil preparation Silexan was investigated in generalized anxiety disorder ( GAD ) in comparison to placebo and paroxetine . In this r and omized , double-blind , double-dummy trial 539 adults with GAD according to DSM-5 criteria and a Hamilton Anxiety Scale ( HAMA ) total score ⩾ 18 points participated and received 160 or 80 mg Silexan , 20 mg paroxetine , or placebo once daily for 10 wk . The primary efficacy endpoint was the HAMA total score reduction between baseline and treatment end . The HAMA total score decreased by 14.1 ± 9.3 points for Silexan 160 mg/d , 12.8 ± 8.7 points for Silexan 80 mg/d , 11.3 ± 8.0 points for paroxetine , and 9.5 ± 9.0 points for placebo ( mean ± s.d . ) . Silexan 160 and 80 mg/d were superior to placebo in reducing the HAMA total score ( p ( HAMA total score reduction : p ) . In the Silexan 160 mg/d group 73/121 patients ( 60.3 % ) showed a HAMA total score reduction ⩾ 50 % of the baseline value and 56 ( 46.3 % ) had a total score for Silexan 80 mg/d , 57/132 ( 43.2 % ) and 45 ( 34.1 % ) for paroxetine , and 51/135 ( 37.8 % ) and 40 ( 29.6 % ) for placebo . In addition , Silexan showed a pronounced antidepressant effect and improved general mental health and health-related quality of life . Incidence densities of adverse events ( AEs ) were 0.006 AEs/d for Silexan 160 mg/d , 0.008 AEs/d for 80 mg/d , 0.011 AEs/d for paroxetine , and 0.008 AEs/d for placebo . In GAD Silexan is more efficacious than placebo . AE rates for Silexan were comparable to placebo and lower than for the active control paroxetine" ]

[ "Background Adjustment for prognostic covariates can lead to increased power in the analysis of r and omized trials . However , adjusted analyses are not often performed in practice . Methods We used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas . We assessed ( 1 ) how large an increase in power can be expected in practice ; and ( 2 ) the impact of adjustment for covariates that are not prognostic . Results Adjustment for known prognostic covariates led to large increases in power for most outcomes . When power was set to 80 % based on an unadjusted analysis , covariate adjustment led to a median increase in power to 92.6 % across the 12 outcomes ( range 80.6 to 99.4 % ) . Power was increased to over 85 % for 8 of 12 outcomes , and to over 95 % for 5 of 12 outcomes . Conversely , the largest decrease in power from adjustment for covariates that were not prognostic was from 80 % to 78.5 % . Conclusions Adjustment for known prognostic covariates can lead to substantial increases in power , and should be routinely incorporated into the analysis of r and omized trials . The potential benefits of adjusting for a small number of possibly prognostic covariates in trials with moderate or large sample sizes far outweigh the risks of doing so , and so should also be considered", "PURPOSE The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue . METHODS Twenty four male Sprague Dawley rats were allotted r and omly to four groups including : control ( taking normal diet ) ; low dose ( supplemented with 0.01 g/kg/day Nigella sativa ) ; normal dose ( supplemented with 0.1 g/kg/day Nigella sativa ) and high dose ( supplemented with 1 g/kg/day Nigella sativa ) . All of supplements administered in powder form mixed with rats ' pellet for 28 days . To assess liver toxicity , liver enzymes measurement and histological study were done at the end of supplementation . RESULTS The finding revealed that there was no significant change in serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) between treatment groups . Histopathological study showed very minimal and mild changes in fatty degeneration in normal and high doses of Nigella sativa treated group . Inflammation and necrosis were absent . CONCLUSION The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg supplemented for a period of 28 days result ed no changes in liver enzymes level and did not cause any toxicity effect on the liver function", "Hypertension ( HT ) is a lifestyle‐related disease and dietary modifications are effective for its management and prevention . We conducted a r and omized , double‐blind , placebo‐controlled trial to evaluate the efficacy of treatment with an oral Nigella sativa ( NS ) seed extract supplement in patients with mild HT . Subjects were r and omized into three groups : a placebo and two test groups that received 100 and 200 mg of NS extract twice a day . After 8 weeks , systolic blood pressure ( SBP ) values in both case groups were found to be significantly reduced when compared with the baseline values for each group . In addition , the decrease in SBP in the two case groups was statistically significant relative to the placebo group ( P , diastolic blood pressure ( DBP ) values in the case groups were found to be significantly reduced from the baseline and a significant reduction was also observed in these groups ( P reduced both SBP and DBP in a dose‐dependent manner . Meanwhile , NS extract caused a significant decline in the level of total and low‐density‐lipoprotein (LDL)‐cholesterol relative to baseline data . No complications caused by NS were observed . The results suggest that the daily use of NS seed extract for 2 months may have a blood pressure‐lowering effect in patients with mild HT", "BACKGROUND Diabetic patients with hypertension and dyslipidemia are at a high risk of cardiovascular complications . OBJECTIVES To determine the effect of Nigella sativa supplementation on the lipid profile , mean arterial pressure , and heart rate in persons with type 2 diabetes on oral hypoglycemic agents ( OHA ) . DESIGN Single-blind , nonr and omized . SETTING Diabetes clinic of a university hospital in Saudi Arabia . PATIENTS AND METHODS Type-2 diabetic patients were recruited by purposive sampling and assigned to treatment or control at the discretion of the investigator with the patient blinded to treatment . Before the intervention and every 3 months thereafter until the end of the treatment period , the following parameters were measured : triglycerides ( TG ) , total cholesterol ( TC ) , low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol ( HDL-C ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , heart rate ( HR ) , and body mass index ( BMI ) . Results at the baseline and each subsequent visit were compared between the two groups . MAIN OUTCOME MEASURE(S ) Lipid and cardiovascular parameters , and BMI . RESULTS Fifty-seven patients were assigned to receive N sativa 2 g daily for one year and 57 were assigned to receive an identical regimen of placebo , along with OHA . A significant decrease in HDL-C and increase in the TC/HDL-C and LDL-C/HDL-C ratios were seen in the control group . The N sativa group had a significant decline in TC , LDL-C , TC/HDL-C and LDL-C/HDL-C ratios , compared with the respective baseline data and the control group . HDL-C was significantly elevated in the N sativa group . The control group showed a significant elevation in MAP . The N sativa group had a significant reduction in SBP , DBP , MAP and HR and a significant decrease in DBP , MAP and HR as compared with the control group . CONCLUSION N sativa supplementation improves total cholesterol , mean arterial pressure and heart rate in type 2 diabetes patients on oral hypoglycemic agents . LIMITATIONS There were 9 subjects in each group lost to follow up ; thus the sample size could not be maintained as per the sample size calculation . The study was nonr and omized and thus there was a possibility of allocation bias . ( Clinical trial registration number : CTRI/2013/06/003781 , Clinical Trial Registry of India )", "Carum carvi L. ( Apiaceae ) is known as caraway , and its derivatives find wide medicinal use for health purpose s , including for gastrointestinal problems and obesity . Since there is inconsistency among the reports on the safety of this plant in humans , this research was aim ed at assessing the safety of a characterized caraway aqueous extract ( CAE ) in a r and omized , triple-blind , placebo-controlled study . Seventy , overweight and obese , healthy women were r and omly assigned into placebo ( n = 35 ) and plant extract ( n = 35 ) groups . Participants received either 30 ml/day of CAE or placebo . Subjects were examined at baseline and after 12 weeks for changes in heart rate , blood pressure , urine test , 25-item blood chemistries , and general health status . No significant changes of blood pressure , heart rate , urine specific gravity , and serum blood tests were observed between the two groups before and after treatment . However , in the complete blood count test , red blood cell levels were significantly ( p platelet distribution width was significantly decreased after the dietary CAE treatment , as compared with placebo . No negative changes were observed in the general health status of the two groups . This preliminary study suggests that the oral intake of CAE appears to be without any adverse effects at a dosage of 30 ml daily for a period of 12 weeks", "The efficacy and safety of the st and ardized herbal combination preparation of Enteroplant , consisting of peppermint oil ( 90 mg ) and caraway ( 50 mg ) in an enteric coated capsule , have been studied in a double-blind , placebo-controlled multicentre trial in patients with non-ulcer dyspepsia . A total of 45 patients were included in the trial after thorough physical and gastro-enterological examination . The primary outcome variables were the change in the intensity of pain and the global clinical impression ( Clinical Global Impression [ CGI ] , Item 2 ) , which were evaluated for 39 patients ( test preparation : 19 , placebo : 20 ) . After four weeks of treatment both target parameters were significantly improved for the group of patients treated with the peppermint oil/caraway oil combination compared to the placebo group ( p = 0.015 and 0.008 , respectively ) . Before the start of treatment all patients in the test preparation group reported moderate to severe pain , while by the end of the study 63.2 % of these patients were free of pain . The pain symptoms had improved in a total of 89.5 % of the patients in the active treatment group . After 4 weeks the Clinical Global Impressions were improved for 94.5 % of the patients treated with the peppermint oil/caraway oil combination . The trial medication was also superior to placebo with respect to pain frequency , medical prognosis , the severity of the disorder and the efficacy index ( CGI , Items 1 and 3 ) , which were adopted as secondary end-points for evaluation of efficacy . There were similarly favourable findings for the herbal combination , compared with placebo , with respect to the reduction of other gastrointestinal symptoms . The combination preparation was found to be excellently tolerated . There was a total of 7 adverse events ( test preparation : 4 , placebo : 3 ) , with a causal association with the treatment being ascribed in one case for the test preparation group and one case for the placebo group", "This study aims to evaluate efficacy and safety of Nigella sativa oil supplementation in patients with chronic kidney disease Stage 3 and 4 due to diabetic nephropathy . It was a prospect i ve , comparative , and open-label study . Patients were r and omized into two groups . Group 1 ( Control ) received conservative management of diabetic nephropathy , whereas Group 2 ( Test ) received N. sativa oil ( 2.5 mL , once daily and per orally ) along with conservative management for 12 weeks . Blood glucose , hemogram , and kidney function test were done at 0 , 6 , and 12 weeks of treatment . Significance of differences between pre- and post-treatment values in each group was assessed using Student 's paired t-test and between the groups using unpaired t-test . We found a drop in blood glucose , serum creatinine , blood urea , and 24 h total urinary protein levels and a rise in glomerular filtration rate , 24 h total urinary volume , and hemoglobin level in the treatment group compared to the control group", "BACKGROUND Experimental evidence s have demonstrated that Nigella sativa Linn . seed ( NS ) has positive modulation effects on aged rats with memory impairments , prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats . NS has neuroprotective , nephroprotective , lung protective , cardioprotective , hepatoprotective activities as established by previous studies on animals . Several clinical trials with NS on human have also demonstrated beneficial effect . AIM OF THE STUDY The present study was design ed to investigate the effects of NS on memory , attention and cognition in healthy elderly volunteers . Furthermore , safety profile of NS was assessed during the nine-week study period . METHODS Forty elderly volunteers were recruited and divided r and omly into group A and group B -- each consisting of 20 volunteers . The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner . All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks . The neuropsychological tests were logical memory test , digit span test , Rey-Osterrieth complex figure test , letter cancellation test , trail making test and stroop test . Safety profile was assessed by measuring biochemical markers of Cardiac ( total cholesterol , triglycerides and high density lipoprotein cholesterol , very low density lipoprotein , low density lipoprotein cholesterol , creatine kinase-MB ) ; Liver ( aspartate aminotransferase , alanin aminotransferase , alkaline phosphatase , total protein , albumin , bilirubin ) and Kidney ( creatinine and blood urea nitrogen ) through using commercial kits . RESULTS There was significant difference ( p score of logical memory test-I and II , total score of digit span , 30 min delayed-recall , percent score in Rey-Osterrieth complex figure test , time taken to complete letter cancellation test , time taken in trail making test-A and test-B , score in part C of stroop test due to ingestion of NS for nine weeks . There were not statistically significant changes ( p>0.05 ) in any of the biochemical markers of cardiac , liver , kidney function during this nine-week study period . CONCLUSIONS The current study demonstrates the role of NS in enhancing memory , attention and cognition . Therefore , whether NS could be considered as potential food supplement for preventing or slow progressing of Alzheimer disease needs further investigations . However , study with Alzheimer 's patients with large population size for longer period of time is recommended before using NS daily and extensive phytochemical investigations are recommended for novel drug discovery from NS for treating cognitive disorders", "Nigella sativa L. seeds ( N. sativa ) have been used as a traditional remedy for a wide range of diseases including hypertension . The present study was performed to explore the effects of N. sativa oil on blood pressure ( BP ) in healthy volunteers . In a double-blind , r and omized study , 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were r and omly allocated to receive 2.5 mL N. sativa oil or placebo two times a day for 8 weeks . The systolic and diastolic BPs , body mass index and blood levels of aspartate transaminase , alanine transaminase , alkaline phosphatase , creatinine and blood urea nitrogen were determined at baseline and endpoint . Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint . Other parameters did not significantly change in both groups at the endpoint . No adverse effects were reported . In conclusion , oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects", "UNLABELLED Diabetes mellitus is a common chronic disease affecting millions of people world wide . St and ard treatment is failing to achieve required correction of blood glucose in many patients . Therefore , there is a need for investigating potential hypoglycemic drugs or herbs to improve glycemic control in diabetic patients . Nigella sativa seeds were used as an adjuvant therapy in patients with diabetes mellitus type 2 added to their anti-diabetic medications . A total of 94 patient were recruited and divided r and omly into three dose groups . Capsules containing Nigella sativa were administered orally in a dose of 1 , 2 and 3 gm/day for three months . The effect of Nigella sativa on the glycemic control was assessed through measurement of fasting blood glucose ( FBG ) , blood glucose level 2 hours postpr and ially ( 2 hPG ) , and glycosylated hemoglobin ( HbA1c ) . Serum C-peptide and changes in body weight were also measured . Insulin resistance and beta-cell function were calculated usin the homeostatic model assessment ( HOMA2 ) . Nigella sativa at a dose of 2 gm/day caused significant reductions in FBG , 2hPG , and HbA1 without significant change in body weight . Fasting blood glucose was reduced by an average of 45 , 62 and 56 mg/dl at 4 , 8 and 12 weeks respectively . HbAlC was reduced by 1.52 % at the end of the 12 weeks of treatment ( P Insulin resistance calculated by HOMA2 was reduced significantly ( P B-cell function was increased ( P Nigella sativa in a dose of 1 gm/day also showed trends in improvement in all the measured parameters but it was not statistically significant from the baseline . However , no further increment in the beneficial response was observed with the 3 gm/day dose . The three doses of Nigella sativa used in the study did not adversely affect either renal functions or hepatic functions of the diabetic patients throughout the study period . IN CONCLUSION the results of this study indicate that a dose of 2 gm/ day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients ", "AIM To evaluate the safety , efficacy and tolerability of Nigella sativa ( N. sativa ) in patients with hepatitis C not eligible for interferon (IFN)-α . METHODS Thirty patients with hepatitis C virus ( HCV ) infection , who were not eligible for IFN/ribavirin therapy , were included in the present study . Inclusion criteria included : patients with HCV with or without cirrhosis , who had a contraindication to IFN-α therapy , or had refused or had a financial constraint to IFN-α therapy . Exclusion criteria included : patients on IFN-α therapy , infection with hepatitis B or hepatitis I virus , hepatocellular carcinoma , other malignancies , major severe illness , or treatment non-compliance . Various parameters , including clinical parameters , complete blood count , liver function , renal function , plasma glucose , total antioxidant capacity ( TAC ) , and polymerase chain reaction , were all assessed at baseline and at the end of the study . Clinical assessment included : hepato and /or splenomegaly , jaundice , palmar erythema , flapping tremors , spider naevi , lower-limb edema , and ascites . N. sativa was administered for three successive months at a dose of ( 450 mg three times daily ) . Clinical response and incidence of adverse drug reactions were assessed initially , periodically , and at the end of the study . RESULTS N. sativa administration significantly improved HCV viral load ( 380808.7 ± 610937 vs 147028.2 ± 475225.6 , P = 0.001 ) and TAC ( 1.35 ± 0.5 vs 1.612 ± 0.56 , P = 0.001 ) . After N. sativa administration , the following laboratory parameters improved : total protein ( 7.1 ± 0.7 vs 7.5 ± 0.8 , P = 0.001 ) , albumin ( 3.5 ± 0.87 vs 3.69 ± 0.91 , P = 0.008 ) , red blood cell count ( 4.13 ± 0.9 vs 4.3 ± 0.9 , P = 0.001 ) , and platelet count ( 167.7 ± 91.2 vs 198.5 ± 103 , P = 0.004 ) . Fasting blood glucose ( 104.03 ± 43.42 vs 92.1 ± 31.34 , P = 0.001 ) and postpr and ial blood glucose ( 143.67 ± 72.56 vs 112.1 ± 42.9 , P = 0.001 ) were significantly decreased in both diabetic and non-diabetic HCV patients . Patients with lower-limb edema decreased significantly from baseline compared with after treatment [ 16 ( 53.30 % ) vs 7 ( 23.30 % ) , P = 0.004 ] . Adverse drug reactions were unremarkable except for a few cases of epigastric pain and hypoglycemia that did not affect patient compliance . CONCLUSION N. sativa administration in patients with HCV was tolerable , safe , decreased viral load , and improved oxidative stress , clinical condition and glycemic control in diabetic patients", "BACKGROUND Inflammation is one of the primary mechanisms in the development of metabolic complications . Although anti-inflammatory characteristics of Nigella sativa ( NS ) have been indicated in animal models , clinical trials related to the effects of NS on inflammatory parameters are relatively scarce . OBJECTIVE The aim of the present study was to determine the effects of NS oil combined with a calorie-restricted diet on systemic inflammatory biomarkers in obese women . METHODS In this double-blind placebo-controlled r and omized clinical trial , 90 volunteer obese ( body mass index = 30 - 34.9 kg/m(2 ) ) women aged 25 - 50 years were recruited . Participants were r and omly divided into two groups , an intervention group ( n = 45 ) and a placebo group ( n = 45 ) . Each group received either : ( 1 ) a low-calorie diet with 3 g/day of NS oil or ( 2 ) a low-calorie diet with 3 g/day placebo for 8 weeks . RESULTS A total of 84 females ( intervention group = 43 ; placebo group = 41 ) completed the trial . Subjects in the intervention group did not report any side effects with the NS oil supplementation . NS oil decreased serum levels of tumor necrosis factor-alpha ( -40.8 % vs -16.1 % , P = .04 ) and high-sensitivity C-reactive protein ( -54.5 % vs -21.4 % , P = .01 ) compared to the placebo group . However , there were no significant changes in interleukin-6 levels ( -8.6 vs -2.4 % , P = .6 ) in the NS group compared to the placebo group . CONCLUSIONS NS oil supplementation combined with a calorie-restricted diet may modulate systemic inflammatory biomarkers in obese women . However , more studies are needed to clarify the efficacy of NS oil as an adjunct therapy to improve inflammatory parameters in obese subjects", "Pre clinical studies have shown beneficial effects of black seed ( Nigella sativa L. ) in the prevention and treatment of renal stones . Hence , we design ed a study to evaluate the renal-stone-dissolving efficacy of black seed . Sixty patients with renal stones were r and omly enrolled in two arms of a r and omized , triple-blind , placebo-controlled , clinical trial . The patients were treated by black seed capsules ( 500 mg ) or placebo two times per day for 10 weeks . Patients were assessed in terms of size of renal stones by using sonography before and after intervention . In the black seed group , 44.4 % of patients excreted their stones completely , and the size of the stones remained unchanged and decreased in 3.7 % and 51.8 % of patients , respectively . In contrast , in the placebo group , 15.3 % of the patients excreted their stones completely , 11.5 % had reduction in stone size , 15.3 % had increase in stone size , and 57.6 % had no change in their stone size . The difference in the mean size of renal stones after the study was significant between the two groups ( p ) . N. sativa L. , as compared with placebo , is demonstrated to have significant positive effects on disappearance or reduction of size of kidney stones", "OBJECTIVE The seed extracts from Nigella sativa is used by Unani physicians of traditional medicine ( Hakims or Tabibs ) and Ayurvedic practitioners ( Vaids ) in the treatment of several medical disorders including dyslipidemia , obesity , and hypertension . It is , therefore , important to prove or disprove the effectiveness , safety , and tolerability of powdered N. sativa ( Kalonji ) seed in capsules on serum lipid levels , blood sugar , blood pressure , and body weight in adults . DESIGN The study design was a r and omized , double-blind trial . SETTING S/LOCATION Conducted at Aga Khan University Hospital , Karachi , from February 2006 to January 2007 . SUBJECTS Half of the respondents received powdered N. sativa ( Kalonji ) seed in capsule and the rest received a placebo . INTERVENTION/ OUTCOME Baseline and after-intervention variables recorded were the following : body-mass index , waist-hip ratio , blood pressure , fasting blood sugar , serum lipids , serum alanine aminotransferase , and serum creatinine . RESULTS One hundred and twenty-three ( 123 ) patients were recruited . Sixty-four ( 64 ) and 59 patients were r and omized to the intervention and the control arms , respectively . Thirty-nine ( 39 ) patients in the intervention group and 34 in the control group completed the study . Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant because of small sample size . CONCLUSIONS Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant . A larger study with adequate sample size is recommended" ]

[ "Abstract Background : The lipid-lowering effect of fenofibrate is accompanied by a rise in plasma homocysteine ( HCY ) , a potential risk factor for venous thromboembolism ( VTE ) . This study investigated the relationship between HCY and the risk of VTE in patients treated with fenofibrate . Methods : The relationship between HCY and deep-vein thrombosis or pulmonary embolism was investigated in 9522 participants of the 5-year Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) trial . All subjects received fenofibrate during a 6-week active run-in phase before r and omization . A Cox proportional-hazards model was used to assess the effect of HCY on risk of venous thromboembolic events . Results : During active-drug run-in , HCY rose on average by 6.5 μmol/L , accompanied by a substantial rise in plasma creatinine ( + 12 % ) . Fenofibrate-induced changes in HCY and creatinine were fully reversible in the placebo group but persisted in the treatment group until reversing at the end of therapy . During follow-up , 1.8 % had at least one episode of deep-vein thrombosis or pulmonary embolism : 103 on fenofibrate and 68 on placebo ( log-rank p=0.006 ) . In multivariate analysis , every 5 μmol/L higher baseline HCY was associated with 19 % higher risk of VTE . Fenofibrate treatment was associated with 52 % higher risk , but the change in HCY with fenofibrate was not significantly associated with VTE after adjustment for baseline HCY . Conclusions : Hyperhomocysteinemia is prospect ively associated with VTE . Fenofibrate may predispose individuals with high pretreatment HCY towards VTE . The fenofibrate-induced increase in HCY did not , however , explain the risk associated with fenofibrate therapy", "This study aim ed to compare the effects of ω-3 fatty acids and fibrate treatment on plasma levels and activities of hemostatic risk factors on glucose and lipid metabolism in subjects with isolated hypertriglyceridemia . Seventy-three subjects with elevated triglyceride levels were allocated into one of the following treatment options : bezafibrate ( 200 mg twice daily ) , ω-3 fatty acids ( 1 g twice daily ) or placebo . Plasma lipids , glucose homeostasis markers ( fasting and 2-h post-glucose load plasma glucose levels and HOMA ) , as well as plasma levels/activities of fibrinogen , factor VII and PAI-1 were determined at baseline , on the day of r and omization , and after 4 and 12 weeks of the treatment . Not only did bezafibrate improve plasma lipids , but it also increased glucose sensitivity and tended to reduce post-glucose loads of plasma glucose . Except for the reduction in plasma triglycerides , ω-3 fatty acids produced no effect on the lipid profile and insulin sensitivity . Both treatment options reduced , to similar extents , plasma levels of fibrinogen and PAI-1 and factor VII coagulant activity . Our study indicates that , although fibrates exhibit more-pronounced metabolic effects than do ω-3 fatty acids , both these treatment options are equipotent in producing a complex beneficial effect on hemostasis in isolated hypertriglyceridemic subjects", " Summary The effects of bezafibrate 400 mg/day ( slow release formulation ) on plasma lipids/lipoproteins and on selected haemostatic parameters were evaluated in a double blind cross-over study in patients with Type IIb and IV hyperlipoproteinaemia . Placebo treatment did not influence any of those parameters , but the drug significantly reduced plasma triglycerides ( −45 % ) and VLDL cholesterol , as well as causing a 12 % fall in total cholesterol and a 20 % increase in HDL cholesterol . Apo AI levels were significantly increased following bezafibrate and Apo B was reduced by about 20 % . In addition to changes in the plasma lipid profile , bezafibrate reduced the sensitivity of platelets to the aggregatory effect of collagen , with no effect on TXB2 production . Fibrinogen levels after bezafibrate treatment were significantly lowered , the effect being more marked in patients with hyperfibrinogenaemia . Bezafibrate did not influence the plasma fibrinolytic profile . It is concluded that bezafibrate , besides its beneficial effects on the plasma lipoprotein profile , can exert beneficial changes on specific haemostatic parameters ", "Summary Background Amputations in people with type 2 diabetes mellitus substantially impair their quality of life and impose high costs on health-care systems . Our aim was to assess the effect of fenofibrate on amputation events in a large cohort of patients with type 2 diabetes . Methods In the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study , 9795 patients aged 50–75 years with type 2 diabetes were r and omly assigned by computer-generated r and omisation sequence to receive fenofibrate 200 mg per day ( n=4895 ) or matching placebo ( n=4900 ) for 5 years ' duration . Information about non-traumatic amputation — a prespecified tertiary endpoint of the study —was routinely gathered . Clinicians who were masked to treatment allocation adjudicated amputations as minor or major ( below or above the ankle , respectively ) . Amputations were also classified on the basis of whether or not large-vessel disease was present in the limb , to distinguish those related to large-artery atherosclerosis from those predominantly related to microvascular disease . Analysis was by intention to treat ( ITT ) . The FIELD study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N64783481 . Findings All 9795 patients were included in the ITT population . 115 patients had one or more non-traumatic lower-limb amputations due to diabetes . Previous cardiovascular disease , microvascular disease , previous non-traumatic amputation or skin ulcer , smoking , and longer duration of diabetes were more frequent in patients who had amputations during the trial than in those who had other cardiovascular events or in those who had neither event ( all p . Mean lipid concentrations differed between patients who had on- study amputations and those who had other cardiovascular events or neither event , but by no more than 0·2 mmol/L. The risks of first amputation ( 45 vs 70 events ; hazard ratio [ HR ] 0·64 , 95 % CI 0·44–0·94 ; p=0·02 ) and minor amputation events without known large-vessel disease ( 18 vs 34 events ; 0·53 , 0·30–0·94 ; p=0·027 ) were lower for patients assigned to fenofibrate than for patients assigned to placebo , with no difference between groups in risk of major amputations ( 24 vs 26 events ; 0·93 , 0·53–1·62 ; p=0·79 ) . Interpretation Classic markers of macrovascular and microvascular risk were associated with lower extremity amputations in patients with type 2 diabetes . Treatment with fenofibrate was associated with a lower risk of amputations , particularly minor amputations without known large-vessel disease , probably through non-lipid mechanisms . These findings could lead to a change in st and ard treatment for the prevention of diabetes-related lower-limb amputations . Funding Laboratoires Fournier SA ( now part of Solvay Pharmaceuticals ) and National Health and Medical Research Council of Australia", "CONTEXT Apart from lowering lipid levels , peroxisome proliferator-activated receptor ( PPAR ) alpha activators ( fibrates ) produce many other favorable effects that may contribute to their clinical effectiveness in dyslipidemic and diabetic patients . OBJECTIVE The objective of this study was to compare the impact of a short-term treatment with fenofibrate and the American Heart Association ( AHA ) step 1 diet on systemic inflammation , hemostasis , and monocyte secretory function in relationship with their metabolic actions . DESIGN , SETTING , PARTICIPANTS , AND INTERVENTIONS This was a prospect i ve , r and omized , placebo-controlled trial involving the group of 91 ambulatory patients with impaired glucose tolerance ( IGT ) ( diagnosed on the basis of the American Diabetes Association criteria ) , r and omly divided into three groups , simultaneously treated for 30 d with the AHA step 1 diet ( n = 30 ) , micronized fenofibrate ( 267 mg/d , n = 31 ) , or placebo ( n = 30 ) . The control group included 34 age- , sex- , and weight-matched subjects with normal glucose tolerance . Eighty-six ( 95 % ) patients and all control subjects completed the study . MAIN OUTCOME MEASURES Plasma markers of inflammation and hemostasis and monocyte release of proinflammatory cytokines were measured . RESULTS Compared with subjects with normal glucose tolerance , IGT patients exhibited higher plasma levels/activities of fibrinogen , factor VII , plasminogen activator inhibitor-1 , high-sensitivity C-reactive protein , and oxidized low-density lipoproteins . Lipopolysaccharide-activated monocytes from IGT patients released significantly more TNF-alpha , IL-1beta , IL-6 , and monocyte chemoattractant protein-1 in comparison with monocytes from control subjects . Thirty-day treatment with fenofibrate but not with the AHA step 1 diet : 1 ) improved lipid/lipoprotein profile and glucose metabolism , and 2 ) reversed or alleviated all the above-mentioned abnormalities . The favorable effects of fenofibrate on plasma high-sensitivity C-reactive protein and on monocyte release of TNF-alpha , IL-1beta , IL-6 , and monocyte chemoattractant protein-1 did not correlate with its action on plasma lipids but was related to the improvement in insulin sensitivity and weakly to free fatty acid-lowering action . CONCLUSIONS Our study is the first to show that relatively small disturbances in glucose metabolism are associated with marked and multidirectional abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function . Moreover , fenofibrate may exhibit early pleiotropic effects in patients with IGT", "Background — The American Heart Association Cardiovascular Health score ( CVH score ) is inversely associated with cardiovascular disease ( CVD ) incidence , but the mechanisms underlying this association warrant exploration . Methods and Results — We related the CVH score to circulating biomarkers and prevalent sub clinical CVD ( defined as ≥1 of the following : increased carotid intima-media thickness or stenosis , left ventricular hypertrophy [ by ECG or echocardiography ] , left ventricular systolic dysfunction , microalbuminuria , and a reduced ankle-brachial index ) in 2680 Framingham Study participants ( mean age , 58 years ; 55 % women ) . After adjustment for age and sex , an ideal CVH score ( nonsmoking status , ideal body mass index , regular physical activity , healthy diet , and an optimal profile of serum cholesterol , blood pressure , and glucose ; 1 point for each ) was associated with higher circulating concentrations of natriuretic peptides ( N-terminal pro-atrial natriuretic peptide and B-type natriuretic peptide ) and lower blood concentrations of plasminogen activator inhibitor-1 , aldosterone , C-reactive protein , D-dimer , fibrinogen , homocysteine , and growth differentiation factor-15 levels ( P The incidence of CVD ( 267 events over 16 years ) was inversely associated with the CVH score in age- and sex-adjusted models ( hazard ratio , 0.77 per 1-unit increase in CVH score ; 95 % confidence interval , 0.70–0.86 ) , which was slightly attenuated upon adjustment for biomarkers and sub clinical disease ( hazard ratio , 0.87 ; 95 % confidence interval , 0.78–0.97 ) . Conclusion — In our prospect i ve community-based study , the inverse association between an ideal cardiovascular health score and CVD incidence was partly attributable to its favorable impact on CVD biomarker levels and sub clinical disease", "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 .", "Low fibrinolytic activity , as measured by euglobulin ( EFA ) , has been observed in obese subjects , and hypofibrinolysis may play a role in the pathogenesis of atherosclerosis and its complications . Blood fibrinolytic activity is regulated through a complex system of activators and inhibitors , especially plasminogen activator inhibitors ( PA Inhibitors ) . In a group of 35 non-diabetic subjects with a wide range of body mass index ( BMI ) , EFA was negatively correlated , and PA Inhibitor activity positively correlated , with BMI and plasma insulin levels . In a population of 49 non-diabetic obese women ( differing from a control group of normal weight by lower EFA and higher level , of PA Inhibitor activity , plasma insulin and triglyceride ) , the PA Inhibitor activity was positively correlated with BMI , insulin and triglyceride . The increase in PA Inhibitor activity was associated with a high value of PA Inhibitor 1 antigen measured by an immuno-radiometric assay , indicating that the increased activity was due to a high level of circulating PA Inhibitor 1 . Plasma insulin was lowered in obese non-diabetic subjects , without modification of the body weight , by a 24 hour fast or by treatment with Metformin . After 24 hours ' fast , ten obese subjects had lower levels of insulin and PA Inhibitor activity and an increase in EFA . Treatment for 15 days by 1.75 g Metformin ( or placebo ) , on a weight maintaining diet , induced , in the Metformin group , a decrease in plasma insulin , triglyceride and PA Inhibitor activity and an increase in EFA , while no change was observed in the placebo group . ( ABSTRACT TRUNCATED AT 250 WORDS", "A r and omized , double-blind , placebo-controlled study was undertaken in 20 hypertriglyceridemic men [ plasma triglyceride ( TG ) , > 2.3 mM ] with low levels ( investigate the ability of micronized fenofibrate ( Tricor or Lipidil ; 200 mg/day ) to affect atherogenic and thrombogenic plasma risk factors in the fed and fasted state . Each patient underwent ( a ) 4 weeks of dietary stabilization , ( b ) 8 weeks of treatment with fenofibrate or placebo , ( c ) a 5-week washout period , and ( d ) 8-weeks of treatment with the alternative medication . An oral fat-loading test ( 1 g fat/kg body weight ) was carried out after both treatment periods . Before treatment , patients had a mean ( + /- SD ) total plasma TG of 3.31+/-0.93 mM ; total C , 5.75+/-0.89 mM ; HDL-C , 0.71+/-0.09 mM ; and low-density lipoprotein (LDL)-C , 3.40+/-0.68 mM. Compared with placebo , fenofibrate reduced fasting TG levels by 36 % , and triglyceride-rich lipoprotein ( TRL , d TRL-C levels by approximately 40 % . In the postpr and ial state , fenofibrate reduced total TG , TRL-TG , TRL-C , TRL-apoC-III , and TRL-apoE levels by -35 % ( all values of p fed HDL-C and apoA-I levels were increased -10 % , and total cholesterol/HDL cholesterol ratios were decreased -15 % by fenofibrate . No significant differences were observed in mean LDL-C and LDL-apoB levels . A 6 % increase in the LDL-C/LDL-apoB ratio during fenofibrate treatment indicated a shift to larger , more buoyant LDL particles . A small , but statistically significant ( p Lp(a ) levels during fenofibrate treatment . Hemostatic parameters were not significantly affected by fenofibrate , except for a 12 - 15 % decrease ( p fibrinogen levels in the fasted and fed state , and a significant increase ( 43 % ; p fasting levels of plasminogen activator-inhibitor-1 . These data demonstrate that micronized fenofibrate is highly effective , in both the fed and fasted state , in reducing TRL lipids and apolipoproteins , and in reducing plasma fibrinogen levels of men with an atherogenic lipoprotein profile", "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", "BACKGROUND Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects . Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus . METHODS The Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study was a multinational r and omised trial of 9795 patients aged 50 - 75 years with type 2 diabetes mellitus . Eligible patients were r and omly assigned to receive fenofibrate 200 mg/day ( n=4895 ) or matching placebo ( n=4900 ) . At each clinic visit , information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study -was gathered . Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema , proliferative retinopathy , or other eye conditions . In a sub study of 1012 patients , st and ardised retinal photography was done and photographs grade d with Early Treatment Diabetic Retinopathy Study ( ETDRS ) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N64783481 . FINDINGS Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors , and in those with a greater burden of clinical microvascular disease , but the need for such treatment was not affected by plasma lipid concentrations . The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group ( 164 [ 3.4 % ] patients on fenofibrate vs 238 [ 4.9 % ] on placebo ; hazard ratio [ HR ] 0.69 , 95 % CI 0.56 - 0.84 ; p=0.0002 ; absolute risk reduction 1.5 % [ 0.7 - 2.3 ] ) . In the ophthalmology sub study , the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall ( 46 [ 9.6 % ] patients on fenofibrate vs 57 [ 12.3 % ] on placebo ; p=0.19 ) or in the subset of patients without pre-existing retinopathy ( 43 [ 11.4 % ] vs 43 [ 11.7 % ] ; p=0.87 ) . By contrast , in patients with pre-existing retinopathy , significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo ( three [ 3.1 % ] patients vs 14 [ 14.6 % ] ; p=0.004 ) . An exploratory composite endpoint of 2-step progression of retinopathy grade , macular oedema , or laser treatments was significantly lower in the fenofibrate group than in the placebo group ( HR 0.66 , 95 % CI 0.47 - 0.94 ; p=0.022 ) . INTERPRETATION Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy , although the mechanism of this effect does not seem to be related to plasma concentrations of lipids", "OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment , administered alone or in sequence , on glucose and lipid metabolism , cardiovascular risk factors , and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia . RESEARCH DESIGN AND METHODS We studied 128 type 2 diabetic patients with mixed dyslipidemia complying throughout the study with lifestyle intervention who were r and omized twice , initially to either metformin or placebo , and then to micronized fenofibrate or placebo . RESULTS Fenofibrate alleviated diabetic dyslipidemia – induced changes in plasma high-sensitivity C-reactive protein , fibrinogen , and plasminogen activator inhibitor (PAI)-1 and in monocyte cytokine release , whereas metformin or lifestyle intervention improved mainly glucose and lipid metabolism . The strongest pleiotropic effect was observed when fenofibrate was added to metformin . CONCLUSIONS Fenofibrate , particularly administered together with metformin , is superior to metformin and lifestyle intervention in exhibiting beneficial effects on systemic inflammation , hemostasis , and monocyte secretory function in type 2 diabetic patients with mixed dyslipidemia", "In a r and omized , double-blind five-year trial , we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein ( HDL ) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men ( 40 to 55 years of age ) with primary dyslipidemia ( non-HDL cholesterol greater than or equal to 200 mg per deciliter [ 5.2 mmol per liter ] in two consecutive pretreatment measurements ) . One group ( 2051 men ) received 600 mg of gemfibrozil twice daily , and the other ( 2030 men ) received placebo . Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total , low-density lipoprotein ( LDL ) , and non-HDL cholesterol and triglycerides . There were minimal changes in serum lipid levels in the placebo group . The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group -- a reduction of 34.0 percent in the incidence of coronary heart disease ( 95 percent confidence interval , 8.2 to 52.6 ; P less than 0.02 ; two-tailed test ) . The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study . There was no difference between the groups in the total death rate , nor did the treatment influence the cancer rates . The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia ", "We investigated the effects of fenofibrate , peroxisome proliferator-activated receptors ( PPARs ) agonist , on endothelial function in patients with hypertriglyceridemia . We administered placebo or fenofibrate 200 mg daily to 25 patients with hypertriglyceridemia for 8 weeks . This study was r and omized , double-blind , placebo-controlled , crossover in design . Compared with placebo , fenofibrate significantly changed lipoprotein levels including non-HDL cholesterol and significantly improved the percent flow-mediated dilator response to hyperemia by 13 + /- 6 % ( P plasma levels of tumor necrosis factor-alpha by 13 + /- 3 % ( P fibrinogen and plasminogen activator inhibitor type 1 antigen levels by 17 + /- 3 and 10 + /- 3 % , respectively ( P plasma levels of nitrate , malondialdehyde , tissue factor activity , and serological markers of plaque stabilization . Fenofibrate significantly changed lipoprotein levels and improved the percent flow-mediated dilator response to hyperemia as well as lowered levels of tumor necrosis factor-alpha ( TNF-alpha ) , fibrinogen , and plasminogen activator inhibitor type 1 antigen", "Impaired fibrinolytic function , mainly due to increased plasma plasminogen activator inhibitor-1 ( PAI-1 ) activity , is common in patients with manifest coronary artery disease ( CAD ) and a predictor of recurrent cardiovascular events . We investigated the relationships of plasma tissue-type plasminogen activator ( tPA ) and PAI-1 antigen levels , plasma PAI-1 activity and PAI 4/5-guanosine ( 4G/5 G ) genotype to CAD progression in 203 middle-aged men participating in the Lopid Coronary Angiography Trial ( LOCAT ) . A higher tPA antigen concentration , whether baseline or on-trial , was associated with a more severe global angiographic response ( p Plasma PAI-1 activity and mass concentration and 4G/5 G PAI-1 genotype were unrelated to angiographic outcome measurements . tPA and PAI-1 antigen increased significantly in the gemfibrozil group ( + 11.3 % and + 16.4 % , respectively , p activity ( median change 0.0 % ) . It is concluded that fibrinolytic function does not substantially influence progression of CAD as assessed by angiography in middle-aged men . Furthermore , pronounced long-term lowering of serum triglycerides by gemfibrozil treatment does not significantly affect the plasma PAI-1 activity level but increases the plasma tPA and PAI-1 antigen concentrations", "Hypertriglyceridemia is linked to impaired fibrinolytic function , and lipid-lowering treatment with fibric acid derivatives could hypothetically improve fibrinolysis in this condition . We therefore conducted a double-blind , placebo-controlled , crossover study of gemfibrozil treatment on fibrinolytic function in 21 men with combined hyperlipoproteinemia . Measurements were performed at rest and during mental stress and after venous occlusion . The patients had clearly disturbed fibrinolytic function , with elevated plasminogen activator inhibitor-1 ( PAI-1 ) activity at rest ( approximately 25 U/mL ; reference , Gemfibrozil reduced plasma total and VLDL cholesterol as well as all triglyceride fractions , whereas HDL cholesterol increased ( P Total triglyceride levels were reduced by 57 + /- 4 % ( from 5.3 to 2.1 mmol/L ) . Fasting serum insulin levels were not altered by gemfibrozil treatment . Plasma levels of PAI-1 activity and tissue-type plasminogen activator ( TPA ) activity or antigen were unaffected by gemfibrozil treatment both at rest and during the provocations . The levels of D-dimer , plasmin/antiplasmin complex , and fibrinogen were also uninfluenced by gemfibrozil treatment . Mental stress elevated plasma TPA ( P=.0036 ) and lowered PAI-1 ( P=.0012 ) activity during placebo but not gemfibrozil treatment ( P=.28 and P=.17 , respectively ) , but treatment effects did not differ by ANOVA on delta values ( ie , stress minus rest ) . Venous occlusion reduced PAI-1 activity , whereas TPA and plasmin/antiplasmin complex increased during both treatments . Thus , gemfibrozil treatment did not improve fibrinolysis or lower fibrinogen levels in men with combined hyperlipoproteinemia despite marked reduction of plasma triglyceride levels . It seems unlikely that improved fibrinolysis explains the primary preventive effect of gemfibrozil", "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", "We have investigated the effects of two fibric acid derivatives , bezafibrate mono ( 400 mg daily ) and gemfibrozil ( 600 mg b.d . ) , in 29 patients with type IIb hyperlipoproteinaemia . All patients received placebo and each drug for 8 weeks in r and omised order in a double-blind , cross-over study design ed to evaluate any different effects of the drugs on serum lipoproteins , cholesteryl ester transfer protein ( CETP ) , cholesteryl ester transfer activity ( CETA ) , plasma fibrinogen , plasminogen activator inhibitor-I ( PAI-1 ) or paraoxonase . Serum cholesterol decreased ( P gemfibrozil , but the effect of bezafibrate on serum cholesterol did not achieve statistical significance ( placebo 8.34 + /- 1.05 ( mean + /- S.D. ) , gemfibrozil 7.70 + /- 1.23 and bezafibrate 7.8 + /- 1.37 mmol/l ) . Both drugs decreased the serum triglyceride concentration ( both P placebo 4.39 ( 3.13 - 5.75 ) ( median ( interquartile range ) ) , bezafibrate 2.26 ( 1.89 - 3.89 ) and gemfibrozil 2.00 ( 1.30 - 3.30 ) mmol/l ) and very low density lipoprotein ( VLDL ) cholesterol ( both P placebo 1.18 ( 0.74 - 2.30 ) , bezafibrate 0.59 ( 0.34 - 0.85 ) and gemfibrozil 0.48 ( 0.34 - 0.68 ) mmol/l ) . Discontinuous gradient ultracentrifugation ( DGU ) revealed that Sf 60 - 400 ( large VLDL ) decreased by more than 50 % and Sf 20 - 60 ( small VLDL ) by more than 30 % with each of the drugs ( both P Gemfibrozil decreased the concentration of Sf 12 - 20 lipoprotein ( intermediate density lipoprotein ; IDL ) by 23 % ( P bezafibrate on this lipoprotein did not achieve statistical significance . Neither drug altered the concentration of apolipoprotein B or of total Sf 0 - 12 lipoproteins ( low density lipoprotein , ( LDL ) ) . Both , however , significantly increased the quantity of free cholesterol in Sf 0 - 12 lipoproteins ( P concentration of triglycerides decreased significantly in all lipoproteins isolated by DGU ( Sf 0 - 12 , Sf 12 - 20 , Sf 20 - 60 , Sf 60 - 400 ) on gemfibrozil treatment , but only in Sf 20 - 60 and Sf 60 - 400 on bezafibrate ( all P serum high density lipoprotein ( HDL ) cholesterol ( placebo 1.15 + /- 0.29 , bezafibrate 1.27 + /- 0.38 ( P gemfibrozil 1.26 + /- 0.49 ( P HDL3 cholesterol concentration ( placebo 0.59 + /- 0.12 , bezafibrate 0.72 + /- 0.23 ( P gemfibrozil 0.70 + /- 0.24 ( P Serum apolipoprotein A1 ( apo A1 ) was increased ( P bezafibrate compared to gemfibrozil ( placebo 103 + /- 26 , bezafibrate 111 + /- 28 and gemfibrozil 102 + /- 25 mg/dl ) and CETA from HDL to VLDL and LDL was decreased ( P bezafibrate compared to placebo , but the apparent decrease with gemfibrozil did not achieve statistical significance ( placebo 39.6 + /- 17.7 , bezafibrate 32.3 + /- 14.7 and gemfibrozil 33.8 + /- 15.0 nmol/ml/h ) . Neither drug affected the circulating concentration of CETP . Plasma fibrinogen was increased ( P gemfibrozil ( placebo 4.16 ( 3.38 - 4.71 ) and gemfibrozil 4.65 ( 4.05 - 5.77 ) g/l ) and was significantly lower ( P bezafibrate ( 3.60 ( 3.18 - 4.54 ) g/l ) than on gemfibrozil treatment . There was a significant ( P PAI-1 activity with bezafibrate and a similar trend with gemfibrozil ( placebo 41.2 ( 25.6 - 64.5 ) , bezafibrate 50.5 ( 35.1 - 73.9 ) and gemfibrozil 48.5 ( 31.5 - 5.4 U/l ) . Neither fibrate influenced plasma concentrations of PAI-1 nor were the activities of lecithin : cholesterol acyl transferase or paraoxonase affected . The major difference in the action of the two drugs on lipoprotein metabolism was the greater effect of gemfibrozil in decreasing the overall serum concentration of Sf 12 - 20 lipoproteins and the triglycerides in Sf 12 - 20 and 0 - 12 lipoproteins . Bezafibrate , however , increased serum apo A1 concentration and significantly decreased CETA . The two drugs also had different effects on the plasma fibrinogen levels , which increased with gemfibrozil and tended to", "The aim of this study was to determine the effect of the lipid modifying agent gemfibrozil on lipid and coagulation risk factors in patients with Type 2 diabetes mellitus ( Type 2 DM ) . Twenty-six subjects with Type 2 DM and dyslipidaemia were treated for 24 weeks with either gemfibrozil 600 mg orally twice daily or placebo in a double-blind r and omized trial . Lipid profiles , fibrinogen , Factor VII , and plasminogen activator inhibitor-1 ( PAI-1 ) were measured by routine laboratory methods . Low density lipoprotein ( LDL ) size was determined by gradient gel electrophoresis and the resistance of LDL to copper-induced oxidation was assessed by measuring absorbance at 234 nm . Gemfibrozil significantly reduced total cholesterol ( -0.9 ( -0.48 , -1.32 ) mmol l(-1 ) ; p triglycerides ( -2.7 ( -1.55 , -1.35 ) mmol l(-1 ) ; p placebo . The fall in triglyceride was reflected by a fall in VLDL cholesterol levels in the gemfibrozil treated group vs placebo ( -1.31 mmol l(-1 ) ; p LDL-cholesterol level did not change but LDL particle size increased by 0.5 nm ( 0.01 , 0.93 ) ; P particle size was inversely correlated with the change of triglyceride level ( r = -0.79 , p susceptibility to copper-induced oxidation . There were no significant changes in the coagulation parameters studied . Because of its ability to correct the lipid abnormalities associated with Type 2 DM particularly hypertriglyceridaemia , gemfibrozil provides a useful therapeutic option in the management of diabetic dyslipidaemia but it does not alter in vitro oxidizability of LDL", "BACKGROUND Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease , partly owing to dyslipidaemia , which can be amenable to fibrate therapy . We design ed the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study to assess the effect of fenofibrate on cardiovascular disease events in these patients . METHODS We did a multinational , r and omised controlled trial with 9795 participants aged 50 - 75 years , with type 2 diabetes mellitus , and not taking statin therapy at study entry . After a placebo and a fenofibrate run-in phase , we r and omly assigned patients ( 2131 with previous cardiovascular disease and 7664 without ) with a total-cholesterol concentration of 3.0 - 6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0 - 5.0 mmol/L to micronised fenofibrate 200 mg daily ( n=4895 ) or matching placebo ( n=4900 ) . Our primary outcome was coronary events ( coronary heart disease death or non-fatal myocardial infa rct ion ) ; the outcome for prespecified subgroup analyses was total cardiovascular events ( the composite of cardiovascular death , myocardial infa rct ion , stroke , and coronary and carotid revascularisation ) . Analysis was by intention to treat . The study was prospect ively registered ( number IS RCT N 64783481 ) . FINDINGS Vital status was confirmed on all but 22 patients . Averaged over the 5 years ' study duration , similar proportions in each group discontinued study medication ( 10 % placebo vs 11 % fenofibrate ) and more patients allocated placebo ( 17 % ) than fenofibrate ( 8 % ; p coronary event ( relative reduction of 11 % ; hazard ratio [ HR ] 0.89 , 95 % CI 0.75 - 1.05 ; p=0.16 ) . This finding corresponds to a significant 24 % reduction in non-fatal myocardial infa rct ion ( 0.76 , 0.62 - 0.94 ; p=0.010 ) and a non-significant increase in coronary heart disease mortality ( 1.19 , 0.90 - 1.57 ; p=0.22 ) . Total cardiovascular disease events were significantly reduced from 13.9 % to 12.5 % ( 0.89 , 0.80 - 0.99 ; p=0.035 ) . This finding included a 21 % reduction in coronary revascularisation ( 0.79 , 0.68 - 0.93 ; p=0.003 ) . Total mortality was 6.6 % in the placebo group and 7.3 % in the fenofibrate group ( p=0.18 ) . Fenofibrate was associated with less albuminuria progression ( p=0.002 ) , and less retinopathy needing laser treatment ( 5.2%vs 3.6 % , p=0.0003 ) . There was a slight increase in pancreatitis ( 0.5%vs 0.8 % , p=0.031 ) and pulmonary embolism ( 0.7%vs 1.1 % , p=0.022 ) , but no other significant adverse effects . INTERPRETATION Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events . It did reduce total cardiovascular events , mainly due to fewer non-fatal myocardial infa rct ions and revascularisations . The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit", "The effects of gemfibrozil on haemostatic variables were studied in 43 survivors of myocardial infa rct ion with serum triglycerides ( TG ) greater than or equal to 2 mmol/l 2 weeks prior to r and omization . The study was double-blind , placebo-controlled and stratified for chronic betablockade . Twenty-two individuals were given gemfibrozil 600 mg twice daily and 21 individuals received matching placebo . After 8 weeks the TG level was unchanged in the placebo group , whereas a 44 % reduction was noted in the gemfibrozil group ( p less than 0.001 ) . Fibrinogen increased in both groups , while bleeding time and platelet count were unchanged . Clotting factor VII-phospholipid complex decreased in both groups , but the change was more marked and attained statistical significance only in the gemfibrozil group ( 60 % reduction , p less than 0.01 ) . By DDAVP-stimulated D-Dimer agglutination test 8 in 21 patients in the placebo group ( 38 % ) still had reduced fibronolytic capacity versus none in the gemfibrozil group ( p = 0.001 ) . Thus , in this study , gemfibrozil improved reduced fibrinolytic capacity and may have reduced hypercoagulability by lowering the clotting factor VII-phospholipid complex" ]

[ "Objective To verify whether the combination of transcutaneous electrical neural stimulation ( TENS ) with oxybutynin in the treatment of women with overactive bladder ( OAB ) would be more effective than isolated treatments . Methods We r and omized 75 women with OAB , in three groups : GI—30 min TENS , twice a week ; GII — daily slow release 10 mg oxybutynin ; and GIII — TENS + oxybutynin ( multimodal ) ; all for 12 weeks . Patients were evaluated with vali date d question naires International Consultation on Incontinence-Short Form ( ICIQ-SF ) , International Consultation on Incontinence-OAB ( ICIQ-OAB ) , Symptom bother , and 3-day Voiding diary at weeks 0 , 12 , and 24 . Results The groups were similar before treatment . After treatment , all groups significantly improved in OAB symptoms and quality of life ( QoL ) . At week 12 , ICIQ-OAB scores were 5.9 , 4.6 , and 2.9 , in groups I , II , and III , respectively , p = 0.01 . At week 24 , GI and GIII kept the scores of the end of treatment ( week 12 ) , while GII increased ICIQ-OAB from 4.6 to 9.2 , p = 0.0001 , ICIQ-SF from 9.8 to 13.3 , p = 0.0006 , and Symptom bother score from 3.4 to 7.0 , p = 0.0001 . Conclusions The multimodal treatment was more effective and TENS alone or in association presented longer lasting results for improvement of clinical symptoms of OAB and", "Purpose This study assessed the benefit of adding behavioural modification to darifenacin treatment for overactive bladder ( OAB ) . Material s and methods The ABLE trial was a r and omised , open-label , parallel-group , multicentre study of 12 weeks of darifenacin treatment [ with voluntary up-titration from 7.5 mg once daily ( qd ) to 15 mg qd at week 2 ] alone or in combination with a Behavioural Modification Programme ( BMP ) for men and women with dry or wet OAB . Efficacy was assessed as the change in the number ( per day ) of micturitions ( primary variable ) , urge urinary incontinence ( UUI ) episodes , urgency episodes , pads used and nocturnal voids . Health-related quality of life ( HRQoL ) was also evaluated . Tolerability and safety assessment s included adverse events and the number of discontinuations . Results Of 592 patients screened , 395 were r and omised , 190 to darifenacin alone and 205 to darifenacin + BMP . At baseline , the majority of subjects were dry ( mean 2.8 and three UUI episodes per day in the darifenacin and darifenacin + BMP groups respectively ) . At study end , darifenacin alone and darifenacin + BMP both produced significant reductions from baseline in median numbers of micturitions , UUI episodes , urgency episodes and nocturnal voids ( all p number of pads used . HRQoL also improved . There were no significant differences between treatment groups in efficacy or HRQoL variables . Conclusions Darifenacin treatment provides a degree of normalisation of micturition variables and improvement in HRQoL that can not be further enhanced by behavioural therapy of the type used in this study . Whether behavioural modification would add benefit over darifenacin treatment in patients with more pronounced incontinence problems remains to be determined", "Background To assess the efficacy and safety of the herbal medicine , Weng-li-tong ( WLT ) as monotherapy or combined with tolterodine in women with overactive bladder ( OAB ) . Methods A prospect i ve , r and omized , single-blind multi-center trial was performed which included 182 OAB patients treated with either placebo ( n = 26 ) , WLT ( n = 52 ) , tolterodine ( n = 52 ) or WLT plus tolterodine ( n = 52 ) . The overactive bladder symptom score ( OABSS ) and micturition behavior were measured to evaluate treatment efficacy . Results In total , 146 patients [ placebo ( n = 23 ) , WLT ( n = 39 ) , tolterodine ( n = 41 ) and WLT plus tolterodine ( n = 43 ) ] completed 8 weeks of treatment . Compared to those treated with placebo , patients in three intervention groups showed significant improvements in the OABSS , voiding frequency , average voided volume and urgency incontinence . WLT had a slower onset than tolterodine or combination therapy in reducing urgency incontinence . Compared with tolterodine , WLT had a weaker effect in improving OABSS ( P = 0.022 ) and daily voiding frequency ( P = 0.034 ) . The combination therapy had better efficacy than WLT or tolterodine alone in improving the OABSS , voiding frequency and voided volume . No significant differences in the changes in quality of life scores were observed among the three intervention groups . Residual urine increased significantly in tolterodine group ( P = 0.004 ) , but not in combination group . WLT result ed in fewer adverse effects than tolterodine such as dry mouth ( P = 0.002 ) , weak stream ( P = 0.002 ) and less residual urine ( P WLT could improve OAB symptoms in women , while it had slower onset and weaker efficacy but fewer adverse effects than tolterodine . The combination of WLT and tolterodine was more efficacious than tolterodine alone in improving OAB symptoms . Trial registration Chinese Clinical Trial Registry [ ChiCTR-IPR-14005626 ] . Date of registration : 7 December 2014", "To evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy , with acceptable tolerability , in the general overactive bladder ( OAB ) population with urinary incontinence ( UI )", "ABSTRACT Purpose To assess effectiveness and durability of Solifenacin ( SS ) versus tibial nerve stimulation ( PTNS ) versus combination therapy ( PTNS + SS ) in women with overactive bladder syndrome ( OAB ) . Material s and Methods 105 women with OAB were divided r and omly into three groups of 35 patients each . In group A women received SS , in group B women underwent PTNS , in group C women underwent combination of PTNS + SS . Improvements in OAB symptoms were assessed with OABSS question naire ; patients ’ quality of life was assessed with OAB-q SF question naire . Evaluation of effectiveness of treatments was performed with PGI-I question naire . OABSS and PGI-I were also assessed monthly for ten months . Results All treatments were effective on symptoms . PTNS showed a greater effectiveness than SS , but PTNS + SS was more effective than SS and PTNS . Furthermore , PTNS + SS showed a greater duration of effectiveness than PTNS and SS . Conclusions Combination of PTNS with SS showed more effectiveness and more durability than PTNS and SS alone", "AIM To evaluate the effect of adding low dose trospium chloride with transcutaneous posterior tibial nerve stimulation ( TPTNS ) in the treatment of overactive bladder ( OAB ) in females after failure of behavioral therapy . METHODS We r and omized 30 women with OAB , in two groups : G I received 30 min TPTNS , three times a week ; GII received TPTNS plus 20 mg trospium chloride daily . OAB Symptom Score question naire ( OABSS ) , Incontinence Impact Question naire-short form 7 ( IIQ-7 ) , 3 day voiding diary and urodynamics at weeks 0 and 8 were evaluated . RESULTS The groups were similar before treatment . Eight weeks after treatment , the mean OABSS decreased significantly to 8.53 ± 1.30 for group II vs 10.0 ± 2.0 for GI ( P The mean IIQ-7 score decreased significantly to 51.86 ± 17.26 in group I vs 31.99 ± 9.26 in group II ( P moderate and poor quality of life ( QoL ) , respectively . After treatment , 6 ( 40 % ) and 14 ( 93.3 % ) had good QoL , 7 ( 46.7 % ) and 1 ( 6.7 % ) had moderate QoL in GI and GII , respectively . Two ( 13.3 % ) patients in GI had poor QoL. The mean frequency was reduced to 8.60 ± 0.83 vs 10.60 ± 2.32 for GII and GI respectively ( P = 0.006 ) . The cystometric capacity increased from 263.40 ± 50.45 to 377.80 ± 112.92 mL ( P = 0.001 ) for GII vs 250.13 ± 56.24 to 296.40 ± 99.0 mL ( P = 0.026 ) for GI . CONCLUSION TPTNS combined with low dose trospium chloride proved to be more effective than TPTNS alone in the treatment of OAB in females", "BACKGROUND Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic ( AM ) agent solifenacin may improve efficacy in the treatment of overactive bladder ( OAB ) while reducing the AM side effects . OBJECTIVE The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5 mg monotherapy . The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy . DESIGN , SETTING , AND PARTICIPANTS A phase 2 , factorial design , r and omised , double-blind , parallel-group , placebo- and monotherapy-controlled trial , conducted at 141 sites in 20 European countries . Male and female patients were aged ≥18 yr with symptoms of OAB for ≥3 mo . INTERVENTION A total of 1306 patients ( 66.4 % female ) were r and omised to 12 wk of treatment in 1 of 12 groups : 6 combination groups ( solifenacin 2.5 , 5 , or 10 mg plus mirabegron 25 or 50 mg ) , 5 monotherapy groups ( solifenacin 2.5 , 5 , or 10 mg , or mirabegron 25 or 50 mg ) , or placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Change from baseline to end of treatment in mean volume voided per micturition ( MVV ) ( primary end point ) and mean numbers of micturitions per 24 h , incontinence episodes per 24 h , and urgency episodes per 24 h were analysed using an analysis of covariance model . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , blood pressure , pulse rate , postvoid residual ( PVR ) volume , and laboratory and electrocardiography ( ECG ) parameters . RESULTS AND LIMITATIONS Compared with solifenacin 5 mg monotherapy , all combinations with solifenacin 5 or 10 mg significantly improved MVV , with adjusted differences ranging from 18.0 ml ( 95 % confidence interval [ CI ] , 5.4 - 30.0 ) to 26.3 ml ( 95 % CI , 12.0 - 41.0 ) . Three combination groups significantly reduced micturition frequency compared with solifenacin 5 mg , ranging from -0.80 ( 95 % CI , -1.39 to -0.22 ) to -0.98 ( 95 % CI , -1.68 to -0.27 ) . Five of six combinations significantly reduced urgency episodes compared with solifenacin 5 mg , ranging from -0.98 ( 95 % CI , -1.78 , to -0.18 ) to -1.37 ( 95 % CI , -2.03 to -0.70 ) . No dose-related trends in TEAEs , blood pressure , pulse rate , PVR volume , or laboratory or ECG parameters were observed between combination and monotherapy groups , although the incidence of constipation was slightly increased with combination therapy . CONCLUSIONS Combination therapy with solifenacin/mirabegron significantly improved MVV , micturition frequency , and urgency compared with solifenacin 5 mg monotherapy . All combinations were well tolerated , with no important additional safety findings compared with monotherapy or placebo . PATIENT SUMMARY To improve treatment of overactive bladder ( OAB ) , mirabegron/solifenacin in combination was compared with each drug alone and placebo . Combination therapy improved OAB symptoms and had similar safety and acceptability . TRIAL REGISTRATION Clinical trials.gov : NCT01340027", "To compare the efficacy of tolterodine plus simplified bladder training ( BT ) with tolterodine alone in patients with an overactive bladder", "INTRODUCTION This study compared percutaneous tibial nerve stimulation ( PTNS ) versus electrical stimulation with pelvic floor muscle training ( ES + PFMT ) in women with overactive bladder syndrome ( OAB ) . MATERIAL S AND METHODS 60 women with OAB were enrolled . Patients were r and omized into two groups . In group A , women underwent ES with PFMT , in group B women underwent PTNS . RESULTS A statistically significant reduction in the number of daily micturitions , episodes of nocturia and urge incontinence was found in the two groups but the difference was more substantial in women treated with PTNS ; voided volume increased in both groups . Quality of life improved in both groups , whereas patient perception of urgency improved only in women treated with PTNS . Global impression of improvement revealed a greater satisfaction in patients treated with PTNS . CONCLUSION This study demonstrates the effectiveness of PTNS and ES with PFMT in women with OAB , but greater improvements were found with PTNS", "Objective : To increase the safety and effectiveness of treatments for overactive bladder ( OAB ) with moderate symptoms in elderly patients . Patients and Methods : Patients were examined at the Urodynamic Department of the Regional Diagnostic Center ( Vladivostok , Russian Federation ) from September 1 , 2012 to December 31 , 2012 . The assignment of patients [ n = 177 , average age 69 . 4 years , 98 women ( 55.4 % ) and 79 men ( 44.6 % ) ] was r and om and blind in this placebo-controlled study . Patients were distributed into subgroups according to the method of treatment as follows : group А1 : n = 57 , trospium 30 mg/day + solifenacin 10 mg/day ; group А2 : n = 61 , trospium 15 mg/day + solifenacin 5 mg/day ; group А3 : n = 59 , placebo . All patients underwent a urodynamic examination in accordance with international st and ards before and 2 months after treatment . ICIQ-SF question naires recommended by the International Continence Society ( ICS ) and bladder diaries were used to evaluate the clinical results . The clinical severity of the OAB symptoms and the effectiveness of the treatment were evaluated based on the frequency of episodes of incontinence ( EI ) per day . Three or fewer EI per day were considered moderate dysfunction of the lower urinary tract . Results : Groups of elderly patients with moderate symptoms of OAB who were treated with st and ard- and low-dose trospium and solifenacin demonstrated a significant increase in the median values of reflex volume , bladder capacity , and detrusor compliance and a decrease in the frequency of urination and urinary urgencies . The frequency of EI in both of the main groups decreased by almost 2-fold in comparison to the initial data and reached the following values : group А1 : 1.27 ( -1.08 ) , p ≤ 0.05 ; group A2 : 1.49 ( -1.18 ) , p ≤ 0.05 . The correlation with the decrease in the frequency of EI in these groups was r = 0.85 ( p ≤ 0.01 ) . The percentage of patients with a significant decrease ( EI ≥1.0 ) among those treated with st and ard- and low-dose trospium and solifenacin increased synchronously , prompting us to suppose the absence of a direct correlation between medicine dose and therapeutic effect for moderate OAB symptoms . Conclusion : The combination of low-dose trospium and solifenacin provides good clinical and urodynamic effects in elderly patients with moderate symptoms of OAB . Combination of these drugs in st and ard doses for such patients is excessive", "PURPOSE We tested whether individualized drug therapy enhanced with behavioral training would result in better outcomes than individualized drug therapy alone . MATERIAL S AND METHODS Participants were community dwelling women with urge predominant incontinence . Using a r and omized clinical trial design women were r and omized to 8 weeks ( 4 visits ) of drug therapy alone ( 32 ) or drug therapy plus behavioral training ( 32 ) . Drug therapy was individually titrated , extended release oxybutynin with proactive management of side effects . Behavioral training included pelvic floor muscle training and urge suppression techniques . The primary outcome measure was reduction in frequency of incontinence episodes on bladder diary at 8 weeks ( with followup at 6 and 12 months ) . Secondary outcomes included patient satisfaction , global perception of improvement , Urogenital Distress Inventory and Incontinence Impact Question naire . RESULTS In intent to treat analysis frequency of incontinence was reduced a mean of 88.5 % in the drug alone group and 78.3 % in the combined therapy group ( p = 0.16 ) . Outcomes were not significantly different between the groups in the analysis of completers ( 91.5 % vs 86.2 % , p = 0.34 ) , or in either analysis at 6 or 12 months . The groups also did not differ significantly on secondary outcomes at any point . Participants in the drug alone group tended to be taking higher doses of oxybutynin at 8 weeks but the final dose did not differ significantly between the groups . Based on a conditional power calculation the trial was stopped early for futility . CONCLUSIONS When drug therapy is implemented with frequent individualized dose titration , daily bladder diaries and careful management of side effects , initiating concurrent behavioral training does not enhance outcomes for urge incontinence in women", "To examine the safety and efficacy of mirabegron as ‘ add‐on ’ therapy to solifenacin in patients with overactive bladder ( OAB )", "We compared the effects of bladder training and /or tolterodine as first line treatment in female patients with overactive bladder ( OAB ) . One hundred and thirty-nine female patients with OAB were r and omized to treatment with bladder training ( BT ) , tolterodine ( To , 2 mg twice daily ) or both ( Co ) for 12 weeks . Treatment efficacy was measured by micturition diary , urgency scores and patients ' subjective assessment of their bladder condition . Mean frequency and nocturia significantly decreased in all treatment groups , declining 25.9 % and 56.1 % , respectively , in the BT group ; 30.2 % and 65.4 % , respectively , in the To group ; and 33.5 % and 66.3 % , respectively in the Co group ( p decrease in frequency was significantly greater in the Co group than in the BT group ( p Mean urgency score decreased by 44.8 % , 62.2 % and 60.2 % in the BT , To , and Co groups , respectively , and the improvement was significantly greater in the To and Co groups than in the BT group ( p controlling OAB symptoms , combination therapy was more effective than either method alone . Tolterodine alone may be instituted as a first-line therapy , but may be more effective when combined with bladder training", "Purpose The aim of this study was to evaluate the effect of desmopressin combined with anticholinergics on daytime frequency and urgency in female patients with overactive bladder ( OAB ) . Material s and Methods We included 68 female patients with OAB . Patients were r and omly assigned to receive 5 mg of solifenacin ( group I ) or 5 mg of solifenacin and 0.2 mg of desmopressin ( group II ) for 2 weeks . A pre/post-treatment 3-day voiding diary and the Urinary Distress Inventory ( UDI-6 ) and Incontinence Impact Question naire ( IIQ-7 ) were used to assess changes in voiding symptoms and quality of life ( QoL ) ; results were compared between the two groups . Results Groups I and II included 31 and 37 patients , respectively . Time to first void was 12 min later in group II ( 105 min vs. 117 min ) , but this difference was not statistically significant . However , time to the second and third voids ( 203 min vs. 255 min , 312 min vs. 368 min ) and the first urgency episode ( 212 min vs. 255 min ) were significantly longer in group II . Compared with group I , patients in group II showed significant improvement in QoL scores . When improvement after treatment was defined as increase in time to first void of greater than 10 % after 2 weeks of treatment , desmopressin with anticholinergics was more effective in patients over the age of 65 years and with more than 150 ml of voided volume . Conclusions Desmopressin combined with anticholinergics was more effective than anticholinergics only in the treatment of female patients with OAB", "AIMS To assess the efficacy and safety of pregabalin alone or in combination with tolterodine extended release ( ER ) in subjects with idiopathic OAB . METHODS This 26-week , multicenter , r and omized , double-blind , placebo-controlled , three-period crossover study enrolled women aged ≥ 18 years that were diagnosed with OAB and reported ≥ 8 micturitions/24 hr and ≥ 4 urgency episodes/week on 5-day bladder diary at baseline . Subjects were r and omized to 1 of 10 treatment sequences and received three of five treatments , each for 4 weeks with 4-week washout periods : st and ard-dose pregabalin/tolterodine ER ( 150 mg twice daily [BID]/4 mg once daily [ QD ] , n=102 ) , pregabalin alone ( 150 mg BID , n=105 ) , tolterodine ER alone ( 4 mg QD , n=104 ) , low-dose pregabalin/tolterodine ER ( 75 mg BID/2 mg QD , n=105 ) , and placebo ( n=103 ) . Subjects completed 5-day diaries at the end of treatment and washout periods . The primary endpoint was change from baseline to week 4 in mean voided volume ( MVV ) per micturition . The primary comparison was st and ard-dose pregabalin/tolterodine ER versus tolterodine ER alone ; secondary comparisons were pregabalin alone versus tolterodine ER alone and versus placebo . RESULTS Baseline-adjusted changes in MVV were significantly greater after treatment with st and ard-dose pregabalin/tolterodine ER ( 39.5 ml ) versus tolterodine ER alone ( 15.5 ml ; P with pregabalin alone ( 27.4 ml ) versus tolterodine ER alone ( P=0.005 ) and placebo ( 11.9 ml ; P=0.0006 ) . Treatments were generally well tolerated ; discontinuation rates due to adverse events were 4 % , 2 % , 5 % , 0 % , and 1 % with st and ard- and low-dose pregabalin/tolterodine ER , pregabalin , tolterodine ER , and placebo , respectively . CONCLUSIONS Pregabalin , alone or with tolterodine ER may offer an alternative treatment option for idiopathic OAB in women", "Study Type – Therapy ( RCT ) Level of Evidence", "Bladder retraining and anticholinergic drugs in women with urge urinary incontinence need to be compared . Women with urge urinary incontinence were recruited by advertisements , from primary care and from a urogynaecology clinic . Women were r and omised using a web page to bladder retraining , anticholinergic drugs or both and followed up at 3 and 12 months . No blinding was attempted . The primary outcomes were the trial process and the Overactive Bladder Question naire ( OAB-q ) quality -of-life measure . Recruitment was much slower than anticipated . There were no differences in the OAB-q at 12 months ( 87.9 SD 11.6 bladder retraining , 81.6 SD 19.3 drug therapy and 88.9 SD 9.9 combination ) but dry mouth was more common in those taking drugs . It is feasible to run a pragmatic r and omised trial with 12-month follow-up for women with urinary urge incontinence . This will require about 500 participants per arm", "Introduction and hypothesisThe objective of this study was to examine the effects of drug therapy alone and combined with behavioral therapy on urgency and 24-voiding frequency in women with urge-predominant incontinence and to identify predictors of change . Methods A planned analysis of data from a multi-site , r and omized , controlled trial ( N = 307 ) . Bladder diaries were used to document voids , incontinence , and urgency severity . Results Urgency scores decreased significantly within both treatment groups , but changes did not differ between groups ( p = 0.30 ) . Improvement in urgency was associated with greater baseline urgency ( p Voiding frequency increased with drug alone and decreased slightly with combined therapy ( p = 0.009 ) , and improvement was associated with combined treatment ( p frequency ( p incontinence episode frequency ( p = 0.001 ) . Conclusions Although combined drug and behavioral therapy does not appear to improve urgency more than drug alone , it result ed in better outcomes on voiding frequency", "Objective : To investigate and compare the effectiveness of various treatment protocol s for the treatment of women with idiopathic detrusor overactivity . Design : Prospect i ve , r and omized controlled trial . Setting : Departments of Physiotherapy and Rehabilitation and Obstetrics and Gynaecology , Hacettepe University . Subjects : Forty-six subjects were r and omized to three groups . Interventions : The first group received only pharmacotherapy , the second group received only physiotherapy and in the third group pharmacotherapy was combined with physiotherapy ( combined therapy group ) . Main measures : All patients were evaluated at the beginning and at the end of treatment . Assessment parameters were maximum cystometric capacity , electromyographic activity of pelvic floor muscles , voiding diary parameters , the amount of urine leakage and the quality of life score . Results : The maximum cystometric capacity and the electromyographic activity of pelvic floor muscles increased significantly and the number of voids/day and incontinence episodes/day , and the amount of urine leakage reduced significantly ( P physiotherapy and combined therapy groups while there was no significant difference in the pharmacotherapy group . After treatment , the number of voids/day increased by 0.3 ± 3.4 in the pharmacotherapy group ( P > 0.05 ) and decreased by 5.1 ± 5.5 and 4.7 ± 5.6 in the physiotherapy and combined therapy groups , respectively ( P number of voids/night and the quality of life scores at the end of the treatment . Conclusion : The physiotherapy protocol we introduced in the present study with or without anticholinergic therapy has a substantial positive impact on the treatment of female patients with idiopathic detrusor overactivity", "PURPOSE To evaluate the efficacy of intermittent percutaneous needle sacral nerve stimulation ( IPN-SNS ) in women with idiopathic overactive bladder ( IOAB ) treated with tolterodine . MATERIAL S AND METHODS A total of 240 female patients diagnosed with IOAB were r and omized to receive tolterodine only treatment ( group 1 , n = 120 ) or tolterodine combined with IPN-SNS ( group 2 , n = 120 ) . Each group included 120 participants , who were divided into subgroups depending on whether they had dry OAB ( urinary frequency and urgency ) or wet OAB ( urinary frequency and urgency with urgency incontinence ) . In the treatment group , patients received percutaneous IPN-SNS plus tolterodine ( 2 mg once daily ) , while in the control group , only tolterodine ( 2 mg once daily ) was administered for 3 months . The voiding diary and urodynamic parameters were monitored , and patients ' psychological depression and anxiety scores were recorded before and after treatment . RESULTS There were significantly greater improvements in the conditions of first desire to void ( FDV ) , max­imum cystometric capacity ( MCC ) , and daily average volumes , as well as the daily single maximum voided volumes in group 2 ( P = .001 ) than in group 1 . In addition , there were significantly greater decreases in self-rating depression scale ( SDS ) and self-rating anxiety scale ( SAS ) scores in group 2 compared with group 1 ( P tolterodine plus IPN-SNS can not only improve the symptoms of voiding dysfunction but can also reduce the concomitant depression and anxiety in women with IOAB , there­by improving patients ' quality of life", "Importance Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information . Objective To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence . Design , Setting , and Participants Multicenter open-label r and omized trial ( February 2012-January 2015 ) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence . Interventions Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA ( n = 192 ) or sacral neuromodulation ( n = 189 ) . Main Outcomes and Measures Primary outcome , change from baseline mean number of daily urgency urinary incontinence episodes over 6 months , was measured with monthly 3-day diaries . Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Question naire Short Form ( SF ) ; range , 0 - 100 , higher scores indicating worse symptoms ; Overactive Bladder Satisfaction question naire ; range , 0 - 100 ; includes 5 subscales , higher scores indicating better satisfaction ; and adverse events . Results Of the 364 women ( mean [ SD ] age , 63.0 [ 11.6 ] years ) in the intention-to-treat population , 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group ( -3.9 vs -3.3 episodes per day ; mean difference , 0.63 ; 95 % CI , 0.13 to 1.14 ; P = .01 ) . Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Question naire SF for symptom bother ( -46.7 vs -38.6 ; mean difference , 8.1 ; 95 % CI , 3.0 to 13.3 ; P = .002 ) ; treatment satisfaction ( 67.7 vs 59.8 ; mean difference , 7.8 ; 95 % CI , 1.6 to 14.1 ; P = .01 ) and treatment endorsement ( 78.1 vs 67.6 ; mean difference ; 10.4 , 95 % CI , 4.3 to 16.5 ; P P = .36 ) , adverse effects ( 88.4 vs 85.1 ; mean difference , 3.3 ; 95 % CI , -1.9 to 8.5 ; P = .22 ) , and treatment preference ( 92.% vs 89 % ; risk difference , -3 % ; 95 % CI , -16 % to 10 % ; P = .49 ) . Urinary tract infections were more frequent in the onabotulinumtoxinA group ( 35 % vs 11 % ; risk difference , -23 % ; 95 % CI , -33 % to -13 % ; P The need for self-catheterization was 8 % and 2 % at 1 and 6 months in the onabotulinumtoxinA group . Neuromodulation device revisions and removals occurred in 3 % . Conclusions and Relevance Among women with refractory urgency urinary incontinence , treatment with onabotulinumtoxinA compared with sacral neuromodulation result ed in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance . In addition , it result ed in a higher risk of urinary tract infections and need for transient self-catheterizations", "BACKGROUND Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder ( OAB ) and is often difficult to treat with antimuscarinic monotherapy . OBJECTIVE To evaluate the efficacy and the safety and tolerability of combination ( solifenacin 5 mg and mirabegron 50 mg ) versus solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4 wk of solifenacin 5 mg . DESIGN , SETTING , AND PARTICIPANTS OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-wk single-blind run-in were r and omised 1:1:1 to double-blind daily combination or solifenacin 5 or 10 mg for 12 wk . Patients receiving the combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was a change from baseline to end of treatment ( EOT ) in the mean number of incontinence episodes per 24h ( stratified rank analysis of covariance [ ANCOVA ] ) . Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h ( ANCOVA ) and number of incontinence episodes noted in a 3-d diary at EOT ( mixed-effects Poisson regression ) . A trial ( BESIDE ) comparing combination treatment ( solifenacin plus mirabegron ) with one treatment alone ( solifenacin ) tested the superiority of combination versus solifenacin 5 mg , noninferiority ( and potential superiority ) of combination versus solifenacin 10 mg ( key secondary end points ) , and the safety and tolerability of combination therapy versus solifenacin monotherapy . RESULTS AND LIMITATIONS A total of 2174 patients were r and omised to combination ( n=727 ) , solifenacin 5 mg ( n=728 ) , or solifenacin 10 mg ( n=719 ) . At EOT , combination was superior to solifenacin 5 mg , with significant improvements in daily incontinence ( p=0.001 ) , daily micturitions ( p , and incontinence noted in a 3-d diary ( p=0.014 ) . Combination was noninferior to solifenacin 10 mg for key secondary end points and superior to solifenacin 10 mg for improving daily micturitions . All treatments were well tolerated . CONCLUSIONS Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms versus solifenacin 5 or 10 mg , and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg . PATIENT SUMMARY In this 12-wk study , overactive bladder patients who remained incontinent despite initial solifenacin 5 mg treatment received additional treatment with mirabegron 50 mg . Combining mirabegron 50 mg with solifenacin 5 mg was superior to solifenacin 5 mg alone in improving symptoms of incontinence and frequent urination , and it was well tolerated . TRIAL REGISTRATION Clinical Trials.gov NCT01908829", "OBJECTIVE Evaluation of safety and efficacy of desmopressin/tolterodine combination therapy in women . METHODS This double-blind , r and omized , proof-of-concept study enrolled 106 patients ( ≥18 years ) , with overactive bladder ( OAB ) and nocturia , with ≥2 nocturnal voids , receiving a 3-month once-daily combination ( desmopressin 25 µg , orally-disintegrating tablets [ODT]/tolterodine 4 mg [ Detrol ® LA ] ; n = 49 ) or monotherapy ( tolterodine 4 mg/placebo ODT ; n = 57 ) . Primary endpoint was change from baseline in mean number of nocturnal voids . Secondary endpoints were change from baseline in nocturnal voided volume , time to first nocturnal void , and quality -of-life . Post-hoc exploratory analysis were performed for patients with and without baseline nocturnal polyuria ( NP , n = 47 each ) . RESULTS Overall population showed a non-significant reduction in mean number of nocturnal voids with combination versus monotherapy ( full analysis set : adjusted treatment contrast [ TC ] , -0.34 ; P = 0.112 ) . Change in mean nocturnal void volume ( TC , -64.16 mL ; P = 0.103 ) , mean time to first nocturnal void ( TC , 18.00 min ; P = 0.385 ) and Nocturia Impact ( NI ) Diary © scores were comparable . In post-hoc analysis , NP patients showed a benefit with combination versus monotherapy for nocturnal void volume ( P = 0.034 ) and time to first nocturnal void ( P = 0.045 ) , and a non-significant improvement in NI Diary © scores . Safety profile was comparable between treatments . A single transient event of asymptomatic clinical ly significant hyponatremia in combination group resolved subsequently . CONCLUSION Low-dose desmopressin could be safely combined with tolterodine for treating nocturia in women with OAB , with a significant benefit in women with NP . Further , prospect i ve validation studies of combination therapy are warranted in mixed NP/OAB population , based on this favorable proof-of-concept finding", "AIMS To evaluate patient-reported outcomes ( PROs ) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder ( OAB ) from the SYNERGY trial . METHODS Following a 4-week placebo run-in , period patients ( ≥18 years ) with OAB were r and omized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg ( combination 5 + 25 mg ) , solifenacin 5 mg + mirabegron 50 mg , ( combination 5 + 50 mg ) , solifenacin 5 mg , mirabegron 25 mg , mirabegron 50 mg or placebo for 12 weeks , followed by a 2-week washout period . At each visit , PROs related to quality of life , symptom bother , and treatment satisfaction were assessed , including OAB-q Symptom Bother score , health-related quality of life ( HRQOL ) Total score , treatment satisfaction-visual analogue scale ( TS-VAS ) , and patient perception of bladder condition ( PPBC ) question naires . RESULTS Overall , 3527 patients were r and omized into the study , with 3494 receiving double-blind treatment . At end of treatment ( EoT ) , both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups ( nominal P in HRQOL Total scores were observed in the combination groups versus monotherapy groups ( P ≤ 0.002 ) . For both combination groups , the OAB-q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy ( P for many HRQOL parameters , including OAB-q Symptom Bother score , HRQOL Total score , and PPBC ", "Objectives The aims of this study were to compare 12-week outcomes of single-therapy tolterodine ( Detrol LA ) extended release to intravaginal estrogen ( Estrace ) for overactive bladder ( OAB ) symptoms and characterize 24- and 52-week outcomes in women undergoing combined therapy . Methods A single-site r and omized , open-label trial in women with urinary frequency , urgency , nocturia , and /or urgency urinary incontinence symptoms was performed . Fifty-eight participants were r and omized to oral tolterodine extended release daily or intravaginal estradiol cream nightly for 6 weeks then twice per week . The primary outcome was change in Overactive Bladder Question naire ( OAB-q ) symptom bother score at 12 weeks . Secondary outcomes included the Health-Related Quality of Life Question naire ( HRQL ) of the OAB-q and a 3-day bladder diary . At 12 weeks , subjects were offered addition of the alternative therapy with follow-up at 24 and 52 weeks . Results There was no difference in symptom bother score improvement between the tolterodine and intravaginal estradiol groups baseline to 12 weeks ( 20.6 ± 21.7 , −15.8 ± 23.3 , respectively , P = 0.45 ) . There was a significant within-group decrease in symptom bother score from baseline to 12 weeks ( tolterodine , P the HRQL total , urinary incontinence episodes , and median voiding frequency ( all P ⩽ 0.03 ) in the tolterodine group and in the HRQL total score ( P = 0.03 ) in the intravaginal estradiol group , with no differences between groups . Combined therapy outcomes at 24 and 52 weeks compared with single therapy at 12 weeks revealed significant improvement in symptom bother score in the intravaginal estradiol + tolterodine group at 24 and 52 weeks ( 20.0 ± 23.9 , P = 0.008 ; −16.7 ± 23.3 , P = 0.02 , respectively ) . Conclusions Significant within-group improvement in OAB-q symptom bother was noted in both the intravaginal estradiol and tolterodine groups for OAB symptoms , with no difference between groups . Greater improvement from 12-week single therapy to 24 and 52 weeks of combined therapy was noted in the group originally assigned to intravaginal estradiol . The role of combined medical therapy for OAB symptoms needs further investigation", "OBJECTIVE The purpose of this study was to examine the effects of combining behavioral treatment and drug treatment for urge incontinence in community-dwelling older women . DESIGN Modified crossover design ( extension of a r and omized clinical trial ) . Eligible subjects were stratified according to type and severity of incontinence and r and omized to behavioral treatment , drug treatment , or a control condition ( placebo ) . Subjects not totally continent or not satisfied after 8 weeks of a single treatment were offered the opportunity to cross over into combined therapy . SETTING A university-based outpatient geriatric medicine clinic . PARTICIPANTS Subjects in the clinical trial were 197 ambulatory , nondemented , community-dwelling women ( age 55 years or older ) with persistent urge urinary incontinence . Thirty-five subjects participated in combined treatment . INTERVENTION One group of subjects received four sessions ( over 8 weeks ) of biofeedback-assisted behavioral training followed by 8 weeks of behavioral training combined with drug therapy ( oxybutynin chloride individually titrated from 2.5 mg to 15 mg daily ) . The second group received drug therapy first , followed by 8 weeks of drug therapy combined with behavioral training . MEASUREMENTS Bladder diaries completed by subjects before and after each treatment phase were used to calculate change in the frequency of incontinent episodes . RESULTS Eight subjects ( 12.7 % ) crossed from behavioral treatment alone to combined behavioral and drug therapy . Additional benefit was seen in improvement from a mean 57.5 % reduction of incontinence with single therapy to a mean 88.5 % reduction of incontinence with combined therapy ( P = .034 ) . Twenty-seven subjects ( 41.5 % ) crossed from drug therapy alone to combined drug and behavioral treatment . They also showed additional improvement , from a mean 72.7 % reduction of incontinence with single therapy to a mean 84.3 % reduction of incontinence with combined therapy ( P = .001 ) . CONCLUSIONS This study shows that combining drug and behavioral therapy in a stepped program can produce added benefit for patients with urge incontinence", "PURPOSE We investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10 mg . MATERIAL S AND METHODS Patients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were r and omized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg , or solifenacin 5 or 10 mg for 12 weeks . The mirabegron dose was increased from 25 to 50 mg after week 4 . Symptom bother , health related quality of life and patient perception of bladder condition were assessed by OAB-q ( Overactive Bladder Question naire ) and the PPBC ( Patient Perception of Bladder Condition ) question naire , respectively . Responder rates were based on a 50 % reduction in daily incontinence , zero incontinence episodes and fewer than 8 micturitions per 24 hours with minimal important differences in OAB-q and PPBC . RESULTS Overall 2,174 patients with a median age of 59 years were r and omized , including 727 to the combination , 728 to solifenacin 5 mg and 719 to solifenacin 10 mg . Symptom bother , total health related quality of life and its subscales ( coping , concern and social ) , and PPBC were significantly improved with combination vs solifenacin monotherapy ( p incontinence , micturition frequency , symptom bother , health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy . The odds of becoming continent was 47 % and 28 % higher for combination vs solifenacin 5 and 10 mg ( OR 1.47 , 95 % CI 1.17 - 1.84 , p = 0.001 and OR 1.28 ; 95 % CI 1.02 - 1.61 , p = 0.033 , respectively ) . CONCLUSIONS Significantly more patients on the combination achieved clinical ly meaningful improvements in incontinence and micturition frequency . Improvements were accompanied by similar improvements in PPBC , symptom bother and health related quality of life", "Overactive bladder ( OAB ) is a disabling disorder . Treatment of cases with OAB includes behavioral , pharmacological , surgical interventions and peripheral electrical stimulation . The goal of this study was to determine effects of posterior tibial nerve stimulation on sexual function and pelvic disorders in women with Overactive bladder ( OAB ) . Fifty women were r and omly assigned to PTNS ( posterior tibial nerve stimulation ) plus tolterodine or tolterodine alone treatment . Tolterodine group received 4 mg tolterodine daily for three months while the other group received this treatment plus percutaneous tibial nerve stimulation for 12 consequence weeks . Two in PTNS group and 8 in the control group withdrew from the study . Age , education level , and occupation status were not significantly different between two groups . Mean total FSFI and its subscales were not significantly different before and after treatment between two groups . Urine leakage associated with a feeling of urgency and loss of stool or gas from the rectum beyond patient 's control became significantly different after treatment between two groups . Posterior tibial nerve stimulation could help urinary problems in women with a neurologic bladder", "OBJECTIVE To evaluate the efficacy of percutaneous tibial nerve stimulation ( PTNS ) , either alone or combined with an anticholinergic agent , in treating patients with an overactive bladder ( OAB ) in whom previous conservative treatment failed . MATERIAL AND METHODS In this study , we included a total of 30 female patients with OAB in whom all conventional therapies failed between January 2010 and April 2011 . Patients were r and omly divided into three groups : Group 1 , PTNS group ; Group 2 , patients receiving an anticholinergic agent ; and Group 3 , patients receiving both PTNS and anticholinergic agent . PTNS treatment continued for 12 weeks with each session lasting 30 min . RESULTS All parameters of the bladder diary significantly improved in all groups ( p scores measured by question naires ( UDI-6 , IIQ-7 , and OABSS ) revealed significant improvements in all groups . When the improvements in symptoms were compared among the groups , there was a statistically significantly higher improvement in groups 1 and 3 than in Group 2 . CONCLUSION PTNS is a safe , simple , and minimally invasive treatment modality in patients with OAB , and it may be suggested either alone or in combination with anticholinergics when conventional treatments fail", "BACKGROUND Women with urge urinary incontinence are commonly treated with antimuscarinic medications , but many discontinue therapy . OBJECTIVE To determine whether combining antimuscarinic drug therapy with supervised behavioral training , compared with drug therapy alone , improves the ability of women with urge incontinence to achieve clinical ly important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy . DESIGN 2-stage , multicenter , r and omized clinical trial conducted from July 2004 to January 2006 . SETTING 9 university-affiliated outpatient clinics . PATIENTS 307 women with urge-predominant incontinence . INTERVENTION 10 weeks of open-label , extended-release tolterodine alone ( n = 153 ) or combined with behavioral training ( n = 154 ) , followed by discontinuation of therapy and follow-up at 8 months . MEASUREMENTS The primary outcome , measured at 8 months , was no receipt of drugs or other therapy for urge incontinence and a 70 % or greater reduction in frequency of incontinence episodes . Secondary outcomes were reduction in incontinence , self-reported satisfaction and improvement , and scores on vali date d question naires measuring symptom distress and bother and health-related quality of life . Study staff who performed outcome evaluations , but not participants and interventionists , were blinded to group assignment . RESULTS 237 participants completed the trial . According to life-table estimates , the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups ( 41 % in both groups ; difference , 0 percentage points [ 95 % CI , -12 to 12 percentage points ] ) . A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70 % or greater reduction in incontinence at 10 weeks ( 69 % vs. 58 % ; difference , 11 percentage points [ CI , -0.3 to 22.1 percentage points ] ) . Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Question naire ( both P patient satisfaction and perceived improvement but not health-related quality of life . Adverse events were uncommon ( 12 events in 6 participants [ 3 in each group ] ) . LIMITATIONS Behavioral therapy components ( daily bladder diary and recommendations for fluid management ) in the group receiving drug therapy alone may have attenuated between-group differences . Assigned treatment was completed by 68 % of participants , whereas 8-month outcome status was assessed on 77 % . CONCLUSION The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence . Combination therapy has a beneficial effect on patient satisfaction , perceived improvement , and reduction of other bladder symptoms", "Objective : Among lower urinary tract symptoms , urinary frequency is one of the prevalent symptoms in the female population . The objective of this study was to evaluate the effect of bladder training with or without pharmacotherapy in women with only a frequency symptom . Methods : Patients were r and omized to either bladder training alone ( n = 23 ) or propiverine combined with bladder training ( n = 25 ) . All patients were treated during 3 months . Results : At baseline , daytime frequency was higher in the combination therapy group than in the bladder training group ( p = 0.031 ) . No difference in other characteristics was observed in the two groups . After treatment , there was no significant difference of functional bladder capacity and average voided volume between the two groups but daytime frequency was higher in the combination therapy group than in the bladder training group ( p = 0.013 ) . However , the changes of daytime frequency , functional bladder capacity and average voided volume were not significantly different in the groups . Of total patients , 15 ( 65.2 % ) in the bladder training group and 21 ( 84.0 % ) in the combination therapy group were rated as responders ( defined as improved or much improved ) ( p = 0.133 ) . Conclusions : Both bladder training with or without pharmacotherapy may improve the subjective and objec- tive frequency symptom in women with only a frequency symptom . However , we could not find that there was more symptomatic improvement when anticholinergics combined with bladder training were compared with bladder training alone", "Objective . Anti-muscarinic treatment alone and peripheral neuromodulation with concomitant anti-muscarinic treatment were compared in patients with severe overactive bladder . Methods . In this prospect i ve study , 40 women with severe overactive bladder according to the 7-day voiding diary without any prior treatment completed the Incontinence Impact Question naire ( IIQ-7 ) and were r and omised into anti-muscarinic-alone and combination treatment groups . Twenty women received daily 4 mgs of tolterodine orally and in 20 women Stoller afferent neuro-stimulation ( SANS ) therapy was performed concomitantly for 12 weeks to the same anti-muscarinic regimen . After 12 weeks of therapy , two of the patients drop out of the study and remaining patients filled out the IIQ-7 question naire and the 7-day voiding diary again . Pretreatment and post-treatment QoL scores and the 7-day voiding diaries were compared . Mann – Whitney U , Wilcoxon and two sided significance tests were used . Results . Thirty-eight women fulfilling the criteria were included in the study . Severity of overactive bladder symptoms decreased significantly in both treatment groups . However , the decrease in combination treatment group was more significant than the anti-muscarinic-alone group . Adverse events were similar between the two groups . Conclusion . Combining SANS and anti-muscarinic therapy result ed in significantly better clinical outcomes and IIQ-7 scores as compared with anti-muscarinic treatment alone in patients with severe overactive bladder", "BACKGROUND The long-term potential of solifenacin and mirabegron combination treatment for patients with overactive bladder ( OAB ) has not been previously assessed . OBJECTIVES To evaluate the safety and efficacy of solifenacin succinate 5 mg plus mirabegron 50 mg tablets ( combination treatment ) versus solifenacin or mirabegron monotherapy in patients with OAB over 12 mo . DESIGN , SETTING , AND PARTICIPANTS R and omised , double-blind , multicentre , phase 3 trial ( SYNERGY II ) of patients with \" wet \" OAB symptoms ( urinary frequency and urgency with incontinence ) for ≥3 mo . The study was conducted from March 2014 to September 2016 ; with 1829 patients r and omised . The full analysis set was comprised of 1794 patients . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary objective was safety , measured as treatment-emergent adverse events ( TEAEs ) . Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h . RESULTS AND LIMITATIONS The median age was 60 yr ( range 19 - 86 yr ) and 1434 patients ( 80 % ) were female . Overall , 856 patients ( 47 % ) experienced ≥1 TEAE . TEAE frequency was slightly higher in the combination group ( 596 patients , 49 % ; mirabegron 126 patients , 41 % ; solifenacin 134 patients , 44 % ) . Serious TEAEs were reported by 67 patients ( 3.7 % ) ; one was considered possibly treatment-related ( mirabegron group , atrial fibrillation ) . Dry mouth was the most common TEAE ( combination 74 patients , 6.1 % ; solifenacin 18 patients , 5.9 % ; mirabegron 12 patients , 3.9 % ) . Combination therapy was statistically superior to mirabegron and solifenacin for the number of incontinence episodes ( vs mirabegron : adjusted mean difference [ AMD ] -0.5 , 95 % confidence interval [ CI ] -0.7 to -0.2 , p vs solifenacin : AMD -0.1 , 95 % CI -0.4 to 0.1 , p=0.002 ) and micturitions ( vs mirabegron : AMD -0.5 , 95 % CI -0.8 to -0.2 , p vs solifenacin : AMD -0.4 , 95 % CI -0.7 to -0.1 , p=0.004 ) . CONCLUSIONS Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy . This innovative combination is a treatment option that could become widely used in the clinic . PATIENT SUMMARY This study looked at the safety and efficacy of a combination of solifenacin succinate 5 mg plus mirabegron 50 mg tablets over 12 mo in patients with the overactive bladder ( OAB ) symptoms of increased urination frequency , heightened urgency to urinate , and unintentional passing of urine . We compared this treatment with solifenacin succinate 5 mg or mirabegron 50 mg alone , and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms . This novel combination could be an improved treatment option in the clinical setting for patients with OAB . This study is registered at Clinical Trials.gov as NCT02045862", "PURPOSE The Study of Urgent PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms ( SUmiT ) was a multicenter , double-blind , r and omized , controlled trial comparing the efficacy of percutaneous tibial nerve stimulation to sham through 12 weeks of therapy . The improvement in global response assessment , voiding diary parameters , and overactive bladder and quality of life question naires was evaluated . MATERIAL S AND METHODS A total of 220 adults with overactive bladder symptoms were r and omized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or sham therapy . Overactive bladder and quality of life question naires as well as 3-day voiding diaries were completed at baseline and at 13 weeks . Subject global response assessment s were completed at week 13 . RESULTS The 13-week subject global response assessment for overall bladder symptoms demonstrated that percutaneous tibial nerve stimulation subjects achieved statistically significant improvement in bladder symptoms with 54.5 % reporting moderately or markedly improved responses compared to 20.9 % of sham subjects from baseline ( p percutaneous tibial nerve stimulation compared to sham . Voiding diary parameters after 12 weeks of therapy showed percutaneous tibial nerve stimulation subjects had statistically significant improvements in frequency , nighttime voids , voids with moderate to severe urgency and urinary urge incontinence episodes compared to sham . No serious device related adverse events or malfunctions were reported . CONCLUSIONS This pivotal multicenter , double-blind , r and omized , sham controlled trial provides level I evidence that percutaneous tibial nerve stimulation therapy is safe and effective in treating overactive bladder symptoms . The compelling efficacy of percutaneous tibial nerve stimulation demonstrated in this trial is consistent with other recently published reports and supports the use of peripheral neuromodulation therapy for overactive bladder", "ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology", "OBJECTIVE To evaluate the efficacy of combined vaginal pelvic floor electrical stimulation ( PFS ) and local vaginal estrogen in treatment of female overactive bladder ( OAB ) . MATERIAL AND METHODS This is a r and omized controlled trial carried out on 315 perimenopausal females with OAB who were r and omly allocated into 3 equal groups . Group A underwent PFS using vaginal probes twice weekly for 12 sessions . Group B received local vaginal estrogen , whereas group C received both PFS and local estrogen . All patients were evaluated by a voiding diary , quality -of-life question naire , vaginal examination , urine analysis , blood sugar , ultrasonography , and urodynamic study before and after therapy . Patients were followed up 1 week , 3 , and 6 months post-therapy . The analyzed variables included day and night time frequency , incontinence episodes , urgency , quality of life , detrusor overactivity ) , and functional bladder capacity ) . Outcome measure was urge incontinence . RESULTS Within each group , there was a statistically significant improvement in all variables after treatment . Improvement of urgency was better in group C than in groups A and B ( P = .000 , .009 ) . Improvement of incontinence was better in groups A and C than in group B ( P = .005 , .004 ) . Follow-up showed worsening of symptoms within 6 months in all groups except incontinence in group C. CONCLUSION Vaginal PFS and estrogen found to be effective in treating OAB symptoms in perimenopausal females . Estrogen seems to augment the effect of PFS especially in the treatment of urgency incontinence and can delay its recurrence" ]

[ "Underst and ing the impact of rheological properties of food on postpr and ial appetite and glycemic response helps to design novel functional products . It has been shown that solid foods have a stronger satiating effect than their liquid equivalent . However , whether a subtle change in viscosity of a semi-solid food would have a similar effect on appetite is unknown . Fifteen healthy males participated in the r and omized cross-over study . Each participant consumed a 1690 kJ portion of a st and ard viscosity ( SV ) and a high viscosity ( HV ) semi-solid meal with 1000 mg acetaminophen in two separate sessions . At regular intervals during the three hours following the meal , subjective appetite ratings were measured and blood sample s collected . The plasma sample s were assayed for insulin , glucose-dependent insulinotropic peptide ( GIP ) , glucose and acetaminophen . After three hours , the participants were provided with an ad libitum pasta meal . Compared with the SV meal , HV was consumed at a slower eating rate ( P = 0.020 ) , with postpr and ial hunger and desire to eat being lower ( P = 0.019 and P plasma concentration of GIP ( P higher plasma concentration of glucose ( P delayed gastric emptying as revealed by the acetaminophen absorption test ( P food viscosity on insulin or food intake at the subsequent meal . In conclusion , increasing the viscosity of a semi-solid food modulates glycemic response and suppresses postpr and ial satiety , although the effect may be short-lived . A slower eating rate and a delayed gastric emptying rate can partly explain for the stronger satiating properties of high viscous semi-solid foods", "BACKGROUND Many preoperative fasting guidelines suggest that hot tea or coffee with milk added should be considered similar to solid food , allowing an interval of 6 h before commencing anaesthesia . There is little evidence to support these instructions , with recent guidelines undecided on the issue . This study aim ed to establish whether there was a clinical ly significant delay in gastric emptying associated with adding a modest amount of milk to tea . METHODS This r and omized controlled crossover study was conducted in 10 healthy volunteers . The paracetamol absorption technique and real-time ultrasound measurement of the cross-sectional area of the gastric antrum were used to assess gastric emptying after ingestion of 300 ml of black tea or 300 ml of tea with milk ( 250 ml black tea plus 50 ml of full fat milk ) . RESULTS The mean difference in the time to reach the peak paracetamol concentration ( tmax ) was -8 min [ 95 % confidence interval ( CI ) -23.1 to 7 ] in favour of tea with milk . Ultrasound assessment indicated that the geometric mean of the half-time to gastric emptying ( T₁/₂ ) after tea without milk was 22.7 ( 95 % CI 12.7 - 40.9 ) min and after tea with milk 23.6 ( 95 % CI 13.5 - 41.0 ) min ( ratio 1.04 ) ( 95 % CI 0.47 - 2.29 ) . CONCLUSIONS This study demonstrated no difference in gastric emptying times when a modest amount of milk was added to tea . These findings suggest that it may be acceptable to allow patients to add a small quantity of milk to their tea or coffee and follow the same fasting restrictions applied to clear fluids", "BACKGROUND In emergency medicine , the gastric tube ( GT ) has many purpose s , however in prehospital setting s , the only indication is gastric decompression . To date , there is lack of recommendation on the diagnostic methods to verify correct GT placement in prehospital . The aim of this study is to estimate diagnostic accuracy of ultrasound in confirming gastric tubes placement in a prehospital setting . METHOD This was a prospect i ve multicentre study conducted in two French towns ( Marseille and Grasse ) over a one-year period from May 2010 to May 2011 . RESULTS One hundred and thirty patients were included in the study with an M/F sex ratio of 77/53 and a mean age of 55.7±19.8 years . The GT position was confirmed by ultrasound , with direct visualization in the gastric area in 116 of the 130 patients . In 14 cases , the ultrasound failed to visualize the tip of the GT ; these results were due in 2 cases to gas interposition and in 12 cases the GT was shown by final X-ray to be located in the end of the oesophagus . Direct visualization by ultrasound thus has a sensitivity of 98.3 % [ 94 - 99.5 ] and a specificity of 100 % [ 75.7 - 100 ] , a positive predictive value of 100 % and a negative predictive value of 85.7 % , Youden 's index of 0.98 . GT size affects ultrasound visualization ; the larger the GT , the easier it is to see . CONCLUSION Bedside ultrasound thus appears to constitute an effective and reliable diagnostic procedure for confirming correct gastric tube placement in prehospital setting", "1 . This study examined the effects of caloric content ( caloric density and the nature of calories ) on the rate of gastric emptying using the double-sampling gastric aspiration technique . Four test meals of 600 ml ( glucose , 0.1 kcal ml-1 ; pea and whey peptide hydrolysates , both 0.2 kcal ml-1 ; milk protein , 0.7 kcal ml-1 ) were tested in six healthy subjects in r and om order on four separate occasions . 2 . The glucose solution was emptied the fastest with a half-time of 9.4 + /- 1.2 min ( P milk protein the slowest with a half-time of 26.4 + /- 10.0 min ( P pea peptide hydrolysate and whey peptide hydrolysate solutions had half-times of emptying of 16.3 + /- 5.4 and 17.2 + /- 6.1 min , respectively . The rates of gastric emptying for the peptide hydrolysate solutions derived from different protein sources were not different . 3 . Despite the lower rate of gastric emptying for the milk protein solution , the rate of caloric delivery to the duodenum during the early phase of the gastric emptying process was higher than that for the other three solutions ( 46.3 + /- 6 , 63.5 + /- 22 , 62.5 + /- 19 and 113.8 + /- 25 cal min-1 kg-1 for the glucose , pea peptide hydrolysate , whey peptide hydrolysate and milk protein meals , respectively ; P caloric density of the test solutions was linearly related to the half-time of gastric emptying ( r = 0.96 , P calories were delivered to the duodenum ( r = 0.99 , P rate of gastric emptying is a function of the caloric density of the ingested meal and that a linear relationship exists between these variables . Furthermore , the nature of the calories seems to play a minor role in determining the rate of gastric emptying in humans", "Background The association between gastric emptying and gastro-esophageal reflux ( GER ) has been widely recognised from scintigraphic studies . Objective A prospect i ve study to ( a ) vali date US as a means of measuring gastric emptying , ( b ) determine physiological patterns of gastric emptying and ( c ) measure gastric emptying in symptomatic refluxers . Material s and methods Three cohorts were studied : ( a ) Ten babies in whom gastric emptying was measured by US and scintigraphy ; ( b ) gastric emptying in 330 asymptomatic children aged between 15 days and 10 years to determine physiological variations ; and ( c ) gastric emptying in 552 children with GER , manifesting as vomiting or cardiorespiratory problems . Results US and scintigraphic techniques showed general concordance in 90 % of cases . In the remaining 10 % , discordant results were related to overlapping of duodenum and stomach during scintigraphy and shadowing of the gastric antrum by air during US . Tremendous variations were induced by change of feed volume or type of formula , underlining the need for a st and ardised procedure . Twenty-two percent of cases showed a peculiar ' plateau ' which differed significantly from the physiological patterns . Most of these babies had esophagitis or acute life-threatening events . Conclusions Investigation of gastric emptying seems to be a key element in the assessment of children with ' pathological ' GER . US is a safe and cheap alternative to scintigraphy for the assessment of gastric emptying", "BACKGROUND : Aspiration pneumonia remains a serious anesthetic-related complication . A reliable diagnostic tool to assess gastric volume is currently lacking . We recently demonstrated that gastric sonography can provide reliable qualitative and quantitative information about gastric content and volume in healthy volunteers . In the current study , we performed a prospect i ve qualitative and quantitative analysis of the gastric antrum in 200 fasted patients undergoing elective surgery . METHODS : A st and ardized gastric scanning protocol was applied before anesthetic induction . Patients were classified following a 3-point grading system based solely on qualitative sonographic assessment of the antrum in the supine and right lateral decubitus positions . RESULTS : Eighty-six patients were classified as grade 0 ( empty antrum ) ; 107 patients as grade 1 ( minimal fluid volume detected only in the right lateral decubitus position ) ; and 7 patients were classified as grade 2 ( antrum clearly distended with fluid visible in both supine and lateral positions ) . The 3-point grading system correlated with total gastric fluid volume as predicted by a previously reported mathematical model . Essentially grade 0 corresponds to a completely empty stomach , grade 1 corresponds to negligible fluid volumes ( 16 ± 36 mL ) within normal ranges expected for fasted patients , and grade 2 correlates with significantly higher predicted gastric fluid volumes ( 180 ± 83 mL ) beyond previously reported “ safe ” limits . One patient with a grade 2 antrum had an episode of significant regurgitation of gastric contents on emergence from anesthesia . CONCLUSION : We propose a 3-point grading system based exclusively on qualitative sonographic assessment of the gastric antrum that correlates well with predicted gastric volume . This grading system could be a promising “ biomarker ” to assess perioperative aspiration risk . Before it can be applied widely to clinical practice , this diagnostic tool needs to be further vali date d and characterized", "Purpose To assess the feasibility and validity of ultrasonographic measurement of gastric antral cross-sectional area ( usCSA ) in critically ill patients to predict gastric volume and the use of computed tomography ( CT ) as a reference to measure gastric volume . Method This single-center , prospect i ve , cross-sectional study included 55 critically ill patients who had an abdominal CT scan . usCSA measurements were performed within the hour preceding the CT scan . Gastric volumes were measured on the CT scan using semiautomatic software . The feasibility rate , performing conditions ( % “ good ” and “ poor ” ) , internal and external validity of antral usCSA measurements , performed by an ICU physician , were assessed to predict gastric volume . Results Antral usCSA measurements were feasible in 95 % of cases and were positively correlated with gastric volume measured by the CT scan when performed in “ good ” conditions ( 65 % ) ( r = 0.43 ) . There was good reproducibility of measurements ( intraclass correlation coefficient of 0.97 , CI 95 % 0.96–0.99 ) and there was clinical ly acceptable agreement between measurements performed by radiologists and intensivists ( bias −0.12 cm2 ) . The receiver operating characteristic curve identified a cutoff value of 3.6 cm2 that discriminated an “ at-risk stomach ” ( volume > 0.8 mL/kg ) at a sensitivity of 76 % and a specificity of 78 % . Conclusions Ultrasonographic measurement of antral CSA is feasible and reliable in the majority of critically ill patients . This technique could be useful to manage critically ill patients at risk of aspiration or with enteral feeding", "Background : Gastric sonography can provide information about gastric content and volume that can help determine aspiration risk at the bedside . The primary objective of this study is to assess the intrarater and interrater reliability of a previously vali date d method of gastric volume assessment based on gastric antral area . The secondary objective is to evaluate the agreement between two different methods to measure gastric antral area . Methods : Three independent raters performed a st and ardized gastric ultrasound assessment in healthy subjects who had been r and omly allocated to ingest a predetermined volume of clear fluid ( apple juice ) from 0 to 400 ml . Each rater measured the gastric antral area , using twice the two-diameter method and twice the free-tracing method . The rater order was allocated at r and om and raters were unaware of the volume ingested and of one-another ’s measurements . The Guidelines for Reporting Reliability and Agreement Studies were followed for conducting and reporting this study . Results : Twenty-two volunteers were studied . Ultrasound assessment of antral cross-sectional area and volume was found to have “ nearly perfect ” intrarater and interrater reliability ( correlation coefficient > 0.8 ) with maximum differences within 13 % . A Bl and –Altman analysis suggests that the free-tracing method and the two-diameter method are essentially equivalent , within a clinical ly acceptable level of agreement . Conclusions : Ultrasound assessment of gastric volume by clinical anesthesiologists is highly reproducible with high intrarater and interrater reliability . The free-tracing method to measure antral cross-sectional area is equivalent to the two-diameter method", "BACKGROUND & AIMS : Infusion of fat into the small intestine induces satiety . Reducing fat droplet size accelerates fat digestion , but the effect on satiety after ileal fat infusion is not known . The aim of the study was to compare the effects of fat emulsions differing in droplet size ( fine , coarse ) infused in either duodenum or ileum on satiety , gastric emptying and peptide secretion . METHODS In a r and omized single-blind crossover study 15 healthy volunteers received , after intubation with a nasoileal tube , 4 different treatments on 4 consecutive days . After consumption of a liquid meal , 6 g of fine or coarse fat emulsion was infused into duodenum or ileum . Study parameters were satiety , gastric emptying and gut peptides . These parameters were statistically evaluated using ANCOVA . RESULTS In the duodenum , Fine emulsion significantly reduced hunger , increased fullness , delayed gastric emptying , but did not affect peptide secretion versus Coarse . In the ileum , Fine emulsion did not affect hunger , fullness , or gastric emptying , but significantly increased peptide secretion versus Coarse . CONCLUSIONS Compared to larger fat droplets , smaller droplets significantly affect satiety , gastric emptying and gut peptide release , but with the effect being dependent on the intestinal location of fat delivery . DUTCH TRIALREGISTER : NTR1515", "Background : Diabetes-induced gastroparesis is believed to increase fasting gastric fluid volume before elective surgery . Metoclopramide is routinely administered preoperatively to reduce gastric fluid volume in these patients . This study compared nondiabetic controls to non – insulin-dependent and insulin-dependent diabetics to determine the effect of metoclopramide , administered before surgery , on gastric volumes in patients who fasted before surgery . Methods : Control and diabetic patients fasted preoperatively before receiving either placebo or 10 mg intravenous metoclopramide 20 min before induction of anesthesia . After intubation , a gastric tube was placed , and stomach contents were aspirated with volumes compared among the groups . Results : Both groups of diabetic patients were older than the control group , and insulin-dependent patients had a higher incidence of comorbidities compared with the non – insulin-dependent group . Fasting blood sugar and hemoglobin A1C values were higher in both insulin-dependent and non – insulin-dependent patients . Gastric fluid volumes were similar in control , non – insulin-dependent , and insulin-dependent patients ( 8.0 ± 2.6 vs. 9.6 ± 4.1 vs. 17.7 ± 2.5 ml , respectively ) . In insulin-dependent diabetic patients , metoclopramide decreased gastric volume compared with placebo treatment ( 17.7 ± 2.5 vs. 7.8 ± 2.9 ml ; P = 0.027 ) . After stratification , a sub population of patients with poorly controlled diabetes , regardless of type , were identified to have increased gastric residual volumes . Conclusion : In elective surgical patients who have fasted before surgery , gastric volumes are minimal , even in diabetics with severe neuropathic symptoms . Metoclopramide prophylaxis to reduce gastric volumes seems to be unnecessary unless the patient has a prolonged history of poor blood glucose control", "OBJECTIVE To compare scintigraphic measurements of total stomach emptying of a semisolid meal with ultrasonographic measurements of changes in antral area as estimates of antral emptying in type 1 diabetic patients . METHODS Eleven patients with insulin-dependent diabetes mellitus were studied with simultaneous measurements of gastric emptying by scintigraphy and ultrasonography . Patients were imaged immediately after ingestion ( time 0 ) and every 15 minutes over 120 minutes . The gastric emptying rate was expressed as percent reduction in antral cross-sectional area from 15 to 90 minutes after meal ingestion . RESULTS Ultrasonographic measurements showed a postpr and ial maximal antral area at 15 minutes , continuously decreasing with time , and reaching a plateau 45 to 90 minutes after the end of meal ingestion , whereas the scintigraphic counts attained their maximum immediately after the meal and began to fall thereafter . Between 15 and 90 minutes , the residual radioactivity and antral ultrasonographically measured distension curves were concordant . The curves then showed a tendency toward deviation for the last 15 minutes ( median , 51 % versus 59 % at 105 minutes and 40 % versus 57 % at 120 minutes , respectively ) . A strong significant correlation could be seen between the ultrasonographic gastric emptying rate and scintigraphic half-time values ( r = -0.94 ; P half-time values showed a systematic measurement error of 9.9 minutes and a r and om measurement error of 18.6 minutes . CONCLUSIONS The use of st and ardized real-time ultrasonography to determine the gastric emptying rate of semisolid meals in diabetic patients , with the use of the change in gastric antral cross-sectional area in a single section of the stomach 15 and 90 minutes postpr and ially , offers a valid method for clinical practice", "BACKGROUND : Gastric ultrasonography allows qualitative and quantitative assessment of gastric contents and volume in nonobese subjects . In this study , we sought to determine the feasibility of gastric ultrasound in severely obese patients ( body mass index [ BMI ] ≥35 kg/m2 ) . We defined feasibility as the ability to identify a full cross section of the gastric antrum in at least 80 % of subjects when imaged in the right lateral decubitus position . METHODS : This was a prospect i ve cohort study on fasted surgical patients with BMI > 35 kg/m2 . The primary outcome measure was the feasibility of gastric sonography . Secondary outcomes included the distribution of antral grade following an existing 3-point grading system . In addition , the antral cross-sectional area ( CSA ) and gastric volumes in this cohort were compared with historical data from a published study in nonobese individuals . Time to image capture , antral wall thickness , and depth of the antrum are also reported . RESULTS : Sixty patients ( BMI range 35.1–68.7 ) were studied . The antrum was identified in 95 % of subjects in the right lateral decubitus ( 95 % CI , 0.86–0.99 ) and 90 % of subjects in the supine position . Definition of antral grade ( 0–2 ) was possible in 88.3 % ( 95 % CI , 0.77–0.95 ) of cases . As expected , antral grade correlated with antral CSA and gastric volumes ( P severely obese patients have a larger baseline CSA and gastric volume than nonobese patients ( P similar gastric volume per unit of weight ( P = 0.141 ) . CONCLUSIONS : Gastric ultrasound assessment is feasible in fasted severely obese subjects . Our data also suggest that obese individuals present larger antral size and gastric volume than their nonobese counterparts", "INTRODUCTION : Pulmonary aspiration of gastric contents is a serious perioperative complication . Previous models of ultrasound gastric volume assessment are preliminary and have not been vali date d by an external “ gold st and ard . ” In the present study we propose a more accurate model based on prospect i ve data obtained from 108 patients undergoing bedside gastric sonography and upper gastrointestinal endoscopy ( UGE ) . METHODS : Patients undergoing elective UGE were r and omized to ingest one of 6 predetermined volumes of apple juice after an 8-hour fasting period . A cross-sectional area of the antrum in the right lateral decubitus position ( Right lat CSA ) was measured by a blinded sonographer following a st and ardized scanning protocol . Gastric fluid was subsequently suctioned under gastroscopic vision during UGE performed by a blinded gastroenterologist and measured to the nearest milliliter . RESULTS : Data from 108 patients suggest that a previously reported model tends to overestimate gastric volume particularly at low volume states . A new best fit mathematical model to predict gastric fluid volume based on measurements of Right lat CSA is presented . This new model built on a more accurate gold st and ard can be used to estimate gastric volumes from 0 to 500 mL , in nonpregnant adults with body mass index gastric fluid volume using st and ard 2-dimentional bedside ultrasound that has several advantages over previously reported models" ]

[ "The hypothalamo-pituitary-adrenal ( HPA ) axis is modulated by sex hormones . Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone ( CRH ) . The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH , cortisol , testosterone , and rostenedione and 17-hydroxyprogesterone ( 17-OHP ) were assessed in nine premenopausal women ( 44 - 48 years of age ) , before and after ovariectomy . The CRH test was performed before and 8 days after ovariectomy . A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy . The ratio of deltamax and rostenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy , whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity . The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production", "CONTEXT Changes in and rogen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established . OBJECTIVE The objective of this study was to document the effects of age on and rogen levels in healthy women and to explore the effects of natural and surgical menopause . DESIGN , SETTING , AND PARTICIPANTS A cross-sectional study was conducted of 1423 non-healthcare-seeking women , aged 18 - 75 yr , r and omly recruited from the community over 15 months . MAIN OUTCOME MEASURES Serum levels by age of total testosterone ( T ) , calculated free T , dehydroepi and rosterone sulfate , and and rostenedione in a reference group of women free of confounding factors . Women in the reference group had no usage of exogenous steroid therapy ; no history of tubal ligation , hysterectomy , or bilateral oophorectomy ; and no hyperprolactinemia or polycystic ovarian syndrome . The effects of natural and surgical menopause on sex steroid levels were also examined . RESULTS In the reference population ( n = 595 ) , total T , calculated free T , dehydroepi and rosterone sulfate , and and rostenedione declined steeply with age ( P serum and rogen levels by year in women aged 45 - 54 yr showed no independent effect of menopausal status on and rogen levels . In women aged 55 yr or older , those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group . CONCLUSIONS We report that serum and rogen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production . These significant variations in and rogens with age must be taken into account when normal ranges are reported and in studies of the role of and rogens in women", "OBJECTIVE To investigate the cross-sectional associations of hysterectomy and oophorectomy status , chronological age , and body mass index with early postoperative plasma levels of total and free T , DHEAS , and sex hormone-binding globulin ( SHBG ) . DESIGN A cross-sectional study . SETTING University hospital . PATIENT(S ) Ninety-two women age 35 - 47 years who were scheduled for hysterectomy and /or oophorectomy , advocated for benign gynecological pathologies . INTERVENTION(S ) Ninety-two eligible premenopausal women underwent hysterectomy and /or oophorectomy , with plasma T , DHEAS , and SHBG levels assayed before surgery and during the postoperative period . MAIN OUTCOME MEASURE(S ) Effects of time x operation and age x operation interactions between oophorectomized and nonoophorectomized groups and within-subject main effect of time on plasma and rogen levels . RESULT ( S ) Of 92 women , hysterectomy alone was performed in only 49 ( 53.3 % ) cases . Oophorectomy , either unilateral or bilateral , was performed in 35.8 % of cases . Age x within-group interactions exhibited an important difference ( P=.03 ) in total T levels . The time x between- and within-group interaction effects on plasma DHEAS levels of postoperative day 7 , compared with day 1 , were statistically significant ( P SHBG levels during the postoperative period . Age x oophorectomy interaction exhibited a statistically significant change of decline in DHEAS levels on postoperative day 7 ( P=.05 ) . CONCLUSION ( S ) The present study demonstrated a time and operation effect decline in plasma DHEAS levels . In contrast , the time x operation interaction on SHBG levels exhibited an increase toward postoperative day 7", "CONTEXT In postmenopausal women , endogenous bioavailable testosterone ( T ) and estradiol ( E2 ) have been positively associated , and SHBG has been negatively associated , with incident type 2 diabetes ( T2DM ) . Previous studies have not explored possible factors explaining these relationships . OBJECTIVE Our objective was to examine the association of endogenous sex hormones with incident T2DM in postmenopausal women and possible explanatory factors . DESIGN , SETTING , AND PARTICIPANTS The Multi-Ethnic Study of Atherosclerosis ( MESA ) is a prospect i ve study that included 1612 postmenopausal women aged 45 - 84 yr , followed between the years 2000 - 2006 , who were not taking hormone replacement therapy , had no prevalent cardiovascular disease or diabetes , and had complete ascertainment of sex hormones . MAIN OUTCOME MEASURES T2DM was defined based on fasting glucose and /or treatment for diabetes . RESULTS There were 116 incident cases of diabetes during follow-up . Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG , we found significantly greater hazards of developing incident T2DM ( all P for trend SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models ( both P for trend Dehydroepi and rosterone had no relationship with incident T2DM . CONCLUSIONS Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women", "In postmenopausal women , levels of estrogens , and rogens , and perhaps prolactin have been related to risk of breast and other hormonal cancers in women . However , the determinants of these hormone concentrations have not been firmly established . Associations among various demographic , menstrual , and reproductive factors , medication use and endogenous sex hormone concentrations ( estradiol , free estradiol , estrone , estrone sulfate , testosterone , free testosterone , sex hormone binding globulin , and rostenedione , dehydroepi and rosterone ( DHEA ) , DHEA sulfate ( DHEAS ) , dihydrotestosterone , and prolactin ) were evaluated in a cross-sectional analysis from a simple r and om sample of 274 postmenopausal women selected from the Women ’s Health Initiative Dietary Modification Trial . In multiple regression analyses on log-transformed hormones , the concentrations of DHEA , and DHEAS were negatively and statistically significantly associated with age ( both β = −0.03 , P ) . Estradiol , estrone , DHEA , and free testosterone concentrations were higher in African-American than in non-Hispanic White women , but after multivariate adjustment the associations were statistically significant only for free testosterone ( β = 0.38 , P = 0.01 ) . Women who had a history of bilateral oophorectomy had a mean 35 % lower testosterone concentration compared with women with at least one ovary remaining ( β = −0.43 , P = 0.002 ) , and lower free testosterone ( β = −0.42 , P = 0.04 ) after multivariate adjustment . Women who reported regular use of NSAIDs had higher DHEA concentrations ( β = 0.20 , P = 0.04 ) and lower prolactin concentrations ( β = −0.18 , P = 0.02 ) compared with non-users . These results suggest that while age , oophorectomy status , and NSAID use may be associated with selected sex hormone concentrations , few menstrual or reproductive factors affect endogenous sex hormones in the postmenopausal period", "BACKGROUND The ovaries provide approximately half the circulating testosterone in premenopausal women . After bilateral oophorectomy , many women report impaired sexual functioning despite estrogen replacement . We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause . METHODS Seventy-five women , 31 to 56 years old , who had undergone oophorectomy and hysterectomy received conjugated equine estrogens ( at least 0.625 mg per day orally ) and , in r and om order , placebo , 150 microg of testosterone , and 300 microg of testosterone per day transdermally for 12 weeks each . Outcome measures included scores on the Brief Index of Sexual Functioning for Women , the Psychological General Well-Being Index , and a sexual-function diary completed over the telephone . RESULTS The mean ( + /-SD ) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter ( 4.2+/-2.8 pmol per liter ) during placebo treatment to 3.9+/-2.4 pg per milliliter ( 13.5+/-8.3 pmol per liter ) and 5.9+/-4.8 pg per milliliter ( 20.5+/-16.6 pmol per liter ) during treatment with 150 and 300 microg of testosterone per day , respectively ( normal range , 1.3 to 6.8 pg per milliliter [ 4.5 to 23.6 pmol per liter ] ) . Despite an appreciable placebo response , the higher testosterone dose result ed in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women ( P=0.03 for both comparisons with placebo ) . At the higher dose the percentages of women who had sexual fantasies , masturbated , or engaged in sexual intercourse at least once a week increased two to three times from base line . The positive-well-being , depressed-mood , and composite scores of the Psychological General Well-Being Index also improved at the higher dose ( P=0.04 , P=0.03 , and P=0.04 , respectively , for the comparison with placebo ) , but the scores on the telephone-based diary did not increase significantly . CONCLUSIONS In women who have undergone oophorectomy and hysterectomy , transdermal testosterone improves sexual function and psychological well-being", "Summary To define the principal characteristics of X-autosome translocations , the authors present a study of 105 cases , five of which are personal observations . The autosomal pairs 15 , 21 , and 22 are affected by t(X-Aut ) more often than would be expected . The distribution of breakpoints on the X chromosome does not differ significantly from the expected distribution . The analysis of different patterns of inactivation seems to confirm that the inactivation could occur at r and om , but would be followed by a cellular selection favoring the better genetic balance . An estimate of the incidence of t(X-Aut ) is proposed , based upon the conclusions that only one chromosome is susceptible to translocation in meiosis in both males and females and that all affected men will be sterile , as will be 50 % of women", "Hormone profiles ( estradiol , testosterone , FSH , LH ) and typical estradiol deficiency phenomena were investigated prospect ively in the first 6 weeks after hysterectomy ( n = 50 ) and after additional bilateral adnexectomy ( n = 17 ) . In the second group estradiol was replaced transdermally from the 2nd postoperative day ( estradiol patch , 0.05 mg daily ) . In the 1st group 34 % of patients showed a significant decrease in estradiol , 28 % of patients a significant decrease in testosterone on the 3rd postoperative day which was no longer demonstrable after 6 weeks . In the second group no decrease in hormone levels was found . So the estradiol patch can replace estradiol to a sufficient degree and in particular physiologically even after bilateral oophorectomy Subjective complaints improved in both groups . Psychosomatic influence also seems to be of importance", "UNLABELLED We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants . There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures . INTRODUCTION Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures , potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy . We prospect ively tested this hypothesis in the Study of Osteoporotic Fractures ( SOF ) . MATERIAL S AND METHODS We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline . Hip fracture analyses included 708 hip fractures ; vertebral fracture analyses included 267 incident vertebral fractures . Baseline serum estradiol and free testosterone values were available in a small subset of participants . RESULTS AND CONCLUSION There were no significant differences in age , weight , or BMD between the women who underwent postmenopausal oophorectomy ( n = 583 ) and those who did not ( n = 5712 ) . Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy . A history of postmenopausal oophorectomy was not associated with an increased risk of hip ( hazard ratio [ HR ] = 1.1 ; 95 % CI = 0.9 - 1.5 ) or vertebral fracture ( HR = 0.7 ; 95 % CI = 0.5 - 1.2 ) . The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level ( HR = 1.3 ; 95 % CI = 0.5 - 3.2 ) or serum free testosterone level ( HR = 1.7 ; 95 % CI = 0.8 - 3.7 ) to the model . In summary , postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort . These results are in contrast to previous findings , suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully eluci date d and that incidental oophorectomy after menopause should still be considered carefully in each potential patient", "OBJECTIVE To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis . DESIGN Controlled , prospect i ve . SETTING Tertiary research center . PATIENT(S ) Two hundred sixty-six women with 46,XX spontaneous premature ovarian failure . INTERVENTION(S ) Ovarian biopsy in 10 women . MAIN OUTCOME MEASURE(S ) Serum adrenal cortex autoantibodies assessed by indirect immunofluorescence and autoimmune oophoritis assessed by immunohistochemical lymphocyte markers . RESULT ( S ) We obtained a histologic diagnosis of autoimmune oophoritis in four women who tested positive for adrenal cortex autoantibodies and excluded this diagnosis in ovarian biopsies from six women who tested negative for adrenal cortex autoantibodies ( 4/4 vs. 0/6 ) . Women with histologically confirmed autoimmune oophoritis had a greater total ovarian volume as assessed by transvaginal sonography ( 11.4 + /- 5.6 mL vs. 1.5 + /- 0.4 mL ) ( mean + /- SEM ) . They were also more likely to have sub clinical adrenal insufficiency and clinical signs of and rogen deficiency ( 3/4 vs. 0/6 ) . Overall , 10/266 women tested positive for adrenal cortex autoantibodies ( 3.8 % , 95 % confidence interval : 1.8%-6.5 % ) . CONCLUSION ( S ) In women who present with 46,XX spontaneous premature ovarian failure as their primary concern there is a clear association between serum adrenal cortex autoantibodies and the presence of histologically confirmed autoimmune oophoritis", "Objective : We investigated whether there is a relationship between and rogens levels and well-being in pre- and postmenopausal women . Design : We r and omly recruited 1423 women aged 18 to 75 years from the community via the electoral roll . Each provided a morning blood sample and completed the Psychological General Well Being Index question naire on the same day . Women were excluded if they took medication for any psychiatric illness , had abnormal thyroid function , or had documented polycystic ovarian syndrome . Analysis was by linear regression for well-being , including demographic and lifestyle variables as well as serum levels of and rogens . Results : We included 1224 women in the analysis . Being partnered was positively associated with well-being in premenopausal women . In postmenopausal women , well-being was positively related to age and exercising , whereas smoking , obesity , and postmenopausal hormone therapy use were each negatively associated with well-being . None of the measured and rogens ( total and free testosterone , dehydroepi and rosterone sulfate , and and rostenedione ) made an independent contribution to well-being in postmenopausal women ( n = 603 ) . However , for premenopausal women ( n = 621 ) , levels of dehydroepi and rosterone sulfate were independently and positively associated with the domain score for vitality . Conclusions : Our findings do not support an important independent role for and rogens as determinants of well-being in postmenopausal women . That dehydroepi and rosterone sulfate alone is associated with greater vitality in premenopausal women is of interest but requires further evaluation as an a priori hypothesis in another study", "OBJECTIVE RIA-based sex hormone measurements offer only limited precision and specificity in the low concentration range of women . Therefore , we aim ed to establish age-specific reference ranges for serum sex hormone concentrations in women using mass spectrometry and quantile regression . METHODS AND RESULTS Data from 985 women aged 20 - 80 yr , recruited for the prospect i ve Study of Health in Pomerania , were included in the analyses . Quantile regressions models were performed to calculate the age-specific 2.5th and 97.5th percentiles for sex hormone concentrations in women . Serum total testosterone ( TT ) and and rostenedione ( AD ) concentrations were measured by liquid chromatography-t and em mass spectrometry . Measured concentrations of SHBG and TT were used to calculate free testosterone ( free T ) . TT , AD , and free T concentrations showed a distinct age-related decline across 10-yr age groups ( one way ANOVA P hormone reference ranges for TT , AD , and free T were determined across each single year of age and for 10-yr age groups . Reference ranges over the whole age range of 20 - 80 yr were 0.35 - 1.97 nmol/liter for TT , 0.89 - 4.56 nmol/liter for AD , and 0.0025 - 0.0253 nmol/liter for free T. Separate reference ranges were provided for pre- and postmenopausal women as well as after inclusion of women using oral contraceptives or hormone therapy ( n = 1357 ) . CONCLUSION This is the first study to establish age-specific reference ranges for liquid chromatography-t and em mass spectrometry-measured TT and AD and calculated free T concentrations based on quantile regression analyses , accurately accounting for the observed low concentration range and the strong age dependency of these sex hormones in women", "Visceral fat ( VF ) increases with the menopause and is an independent predictor of the metabolic syndrome , diabetes , and cardiovascular disease ( CVD ) in women . Little is known about how hormonal changes during the menopausal transition are related to the increase in VF . We aim ed to determine the relationship between bioavailable testosterone and VF in middle-aged women at various stages of the menopausal transition and whether this relationship is independent of age and other CVD risk factors . The Study of Women 's Health Across the Nation ( SWAN ) is a longitudinal , community-based study . This report uses baseline data from a population -based longitudinal ancillary study at the Chicago site to examine the cross-sectional relationship between testosterone and computed tomography (CT)-assessed VF in women at different stages of the menopausal transition . Included are 359 women ( 47.2 % black ) , aged 42 - 60 years , who were r and omly selected from a complete community census in which a 72 % participation rate was achieved . In multivariate models , bioavailable testosterone was associated with VF independent of age , race , percent total body fat , and other cardiovascular risk factors . Bioavailable testosterone was a stronger predictor than estradiol and was interchangeable in its strength of association with sex hormone-binding globulin ( SHBG ) . As bioavailable testosterone was associated with VF even after adjusting for insulin resistance , this suggests that it plays an important role in regional fat distribution . Our findings may have direct implication s in explaining the effect of menopause-related testosterone predominance on VF accumulation and subsequent cardiovascular risk", "We sought to determine the effects of aging on several aspects of adrenal steroidogenesis in the hopes of characterizing the possible causes of adrenal and rogen deficiency in elderly women . To this end , we quantified basal morning concentrations of cortisol ( F ) , dehydroepi and rosterone ( DHEA ) , dehydroepi and rosterone sulfate ( DS ) , and and rostenedione ( A4 ) and then evaluated the effects of overnight dexamethasone ( DEX ) suppression followed by adrenal responses to grade d hourly infusions of ACTH , ranging from 20 - 1280 ng/1.5 m2 x h. Finally , we performed a st and ard 0.25-mg ACTH bolus stimulation test , with sampling at 1 h thereafter . Basal serum levels of DHEA , DS , and A4 were significantly reduced ( approximately 50 % each ) in a group of 35 healthy postmenopausal women , 55 - 68 yr old , compared to those in 30 healthy , regularly menstruating women , 20 - 25 yr old . Post-DEX levels of these C19 steroids also were significantly lower in the older women than in the younger women ; the percent decrease after DEX for A4 was greater in the older women , whereas those in DHEA and DS were not age related . Basal and post-DEX levels of F were similar in both groups . Secretory responses of DS to ACTH were not informative due to its large plasma pool and slow clearance rate . The maximally stimulated levels of DHEA after ACTH bolus were significantly lower in the older women than in younger women ; those of A4 were similar in both age groups , and the maximally achieved levels of F were higher in the older women than in the younger women . The sensitivity of adrenal DHEA , A4 , and F to ACTH ( defined as the minimal dose of ACTH required to significantly increase the steroid levels above basal post-DEX values ) was similar in older and younger women . The responsiveness of the steroids of interest to ACTH ( defined as the slope of the dose-response curve over the linear portion of the dose-response curve ) also was similar among younger and older women . These data demonstrate that the deficiency in adrenal and rogen production in women is restricted to the delta5-pathway steroid products ( DHEA and DS ) , whereas there is no reduction in the capacity of the adrenal to produce A4 or cortisol . As DHEA and DS are likely to be produced mainly in the zona reticularis of the adrenal cortex , we propose that these data point to an alteration in that cortical zone as the cause of adrenal and rogen deficiency in aging . The reductions in A4 in aging are probably due to reduced ovarian secretion after menopause", "OBJECTIVE Excess weight has been associated with increased risk of cancer at several organ sites . In part , this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides . The objectives of the study were to examine the association of body mass index ( BMI ) with circulating and rogens ( testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEAS ) ) , estrogens ( estrone and estradiol ) , sex hormone-binding globulin ( SHBG ) , IGF-I and IGF-binding protein (IGFBP)-3 , and the relationship between sex steroids , IGF-I and IGFBP-3 . DESIGN AND METHODS A cross-sectional analysis was performed using hormonal and question naire data of 620 healthy women ( 177 pre- and 443 post-menopausal ) . The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk . RESULTS In the pre-menopausal group , BMI was not related to and rogens and IGF-I. In the post-menopausal group , estrogens , testosterone and and rostenedione increased with increasing BMI . The association with IGF-I was non-linear , with the highest mean concentrations observed in women with BMI between 24 and 25 . In both pre- and post-menopausal subjects , IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI . As for the correlations between peptide and steroid hormones , in the post-menopausal group , IGF-I was positively related to and rogens , inversely correlated with SHBG , and not correlated with estrogens . In the pre-menopausal group , similar but weaker correlations between IGF-I and and rogens were observed . CONCLUSIONS These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation , especially after menopause . Circulating IGF-I , and rogens and SHBG appear to be related to each other in post-menopausal women", "OBJECTIVE The measurement of total serum testosterone has an established clinical role in the management of male hypogonadism and female and rogen excess disorders . We studied the between-kit variability and precision of six different commercially available testosterone assays and compared them with an established in-house method . DESIGN Laboratory observational prospect i ve study . SETTING Tertiary university medical center clinical laboratory . PATIENT(S ) Three groups of sample s each of men ( n = 36 ) and women ( n = 15 ) who had high , normal , or low levels of sex hormone-binding globulin ( SHBG ) , respectively , were studied . INTERVENTION(S ) Individual and pooled ( male and female ) serum sample s were analyzed for total testosterone concentration using six different commercially available assays and one in-house method . MAIN OUTCOME MEASURE(S ) The between-kit variability and the effect of the mean ( + /- SD ) SHBG level were determined , the results obtained with the use of the kits and the in-house method were compared , and the intraassay variability ( i.e. , precision ) was evaluated . RESULT ( S ) Male sample s demonstrated a 26.3%-40.8 % variance in the results obtained with different kits , which was greatest for sample s with the lowest SHBG levels . For female sample s , between-kit variability ranged from 57%-115 % ( average , 77 % ) . The percent deviation of the results obtained with the use of commercial methods from those obtained with the use of our in-house assay was greater for men ( mean variance , 194 % ) than for women ( mean variance , 67 % ) . The female pool intraassay coefficient of variation was 3.8 % with the use of the in-house method and ranged from 8.9%-21.2 % with the use of the commercial kits . The male pool intraassay coefficient of variation was 3.1 % with the use of the in-house method and ranged from 3.3%-5.5 % with the use of the commercial kits . CONCLUSION ( S ) Most commercially available kits for measuring the total serum testosterone level demonstrated significant between-kit variability , which was greatest for female sample s. Further , sample s with the lowest SHBG levels had the highest between-kit variances . These data strongly suggest that the measurement of total serum testosterone using commercial kits may have limited utility , particularly for the detection of hyper and rogenemia", "CONTEXT Little is known about testosterone ( T ) levels and their determinants in women of late postmenopausal age . OBJECTIVE We describe levels of total and free T and selected factors that influence these levels in a r and om sample of older women . DESIGN Levels of serum total T and free T by microdialysis were measured using ultrasensitive assays in 347 community-dwelling women aged 65 - 98 yr enrolled in the Cardiovascular Health Study . Cross-sectional analyses were performed to define factors associated with total and free T levels . RESULTS In adjusted models : 1 ) total T levels declined with age until 80 , whereas free T levels did not vary by age ; 2 ) women with bilateral oophorectomy had 23 % lower total T and 16 % lower free T levels than those with at least one intact ovary ; 3 ) oral estrogen users had total and free T levels that were 47 % lower than never users ; 4 ) obese women had 47 % higher total T and 20 % higher free T levels , and overweight women had 24 % higher total T and 14 % higher free T levels , than normal weight women ; and 5 ) free T levels were 51 % higher in black women . Corticosteroid users had 75 % lower total T and 43 % lower free T levels than nonusers . CONCLUSIONS Bilateral oophorectomy , estrogen use , corticosteroid use , and low body mass index are independent risk factors for lower T levels in women aged 65 yr and over . Although highly prevalent in women of this age , the physiological significance of low T levels in late postmenopausal women requires further investigation", "Normal menopause is associated with vascular endothelial dysfunction , an early stage of atherosclerosis . The effect of premature ovarian failure ( or premature menopause ) on endothelial function in young women is unknown . Endothelial function was assessed in 18 women with premature ovarian failure before and after 6 months of hormone therapy and was compared with the endothelial function of 20 age- and body mass index-matched premenopausal women . Brachial artery diameter was measured both during hyperemia ( an index of endothelium-dependent vasodilation ) and in response to glyceryl trinitrate ( an index of endothelium-independent vaso-dilation ) . Flow-mediated dilation was significantly lower in women with premature ovarian failure at baseline ( increase in brachial artery diameter during hyperemia by 3.06 + /- 4.33 % ) than in control women ( increase by 8.84 + /- 2.15 % ; P Glyceryl trinitrate-induced vasodilation did not differ between the groups . After hormone therapy for 6 months , flow-mediated dilation was improved in women with premature ovarian failure , increasing by more than 2-fold ( 7.41 + /- 3.86 % ; P Glyceryl trinitrate-induced vasodilation did not change after treatment in women with premature ovarian failure . Young women with premature ovarian failure have significant vascular endothelial dysfunction . Early onset of endothelial dysfunction associated with sex steroid deficiency may contribute to the increased risk of cardiovascular disease and mortality in young women with premature ovarian failure . Hormone therapy restores endothelial function within 6 months of treatment", "OBJECTIVE There is evidence to suggest that the release of neurohypophyseal hormones may be influenced by the circulating concentrations of gonadal steroids . We therefore monitored this relationship in women undergoing prophylactic bilateral oophorectomy at the time of hysterectomy with subsequent hormone replacement therapy and compared it with that in women undergoing hysterectomy with conservation of", "OBJECTIVE To determine whether women with 46,XX spontaneous premature ovarian failure have lower serum free-T levels than do control women . DESIGN Cross-sectional . SETTING National Institutes of Health Clinical Research Center . PATIENT(S ) Women with 46,XX spontaneous premature ovarian failure ( n = 130 ) . INTERVENTION(S ) Evaluation while off any estrogen therapy and then again after receiving a st and ardized hormone regimen . Regularly menstruating control women ( n = 65 ) were sample d during the midfollicular phase . MAIN OUTCOME MEASURE(S ) Serum total T by RIA after extraction and column chromatography , free T by equilibrium dialysis , and sex hormone-binding globulin by immunoradiometric assay . RESULT ( S ) While off estrogen therapy patients had a median serum free-T concentration that was statistically significantly lower than controls ( 2.2 vs. 3.3 pg/mL ) . This dropped significantly lower to 1.9 pg/mL while the patients were on physiologic transdermal E(2 ) therapy . This is despite the fact that sex hormone-binding globulin levels did not change . While on E(2 ) therapy , 13 % of women ( 95 % confidence interval , 7.9%-20.3 % ) had serum free-T levels below the lower limit of normal ( young women with 46,XX spontaneous premature ovarian failure have reduced circulating free-T levels , both during an interval off of estrogen therapy and while on physiologic transdermal E(2 ) therapy", "From a longitudinal prospect i ve study , 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause . After 12 years 152 women were still participating in the study . Blood sample s were drawn every 6 months until 1 year after the menopause and every 12 months thereafter . Measurements of bone mineral density ( BMD ) on the forearm were performed every second year . All women routinely completed a question naire concerning symptoms frequently attributed to the climacteric period . All data were grouped around the onset of the menopause , thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period . The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone ( FSH ) . A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone ( LH ) from about 5 years before the menopause . Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2 - 3 years postmenopause for FSH . Thereafter , a continuous decrease in LH occurred over the following 8 years . With respect to FSH , there was a slight decline starting about 4 years postmenopause . During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and , in the postmenopausal years , the serum levels of progesterone ( P ) were invariably low . Gradually , the ratio between estrone ( E1 ) and 17-beta-estradiol ( E2 ) increased , reflecting the declining follicular steroidogenesis . A marked decrease in estrogen levels occurred during the 6 month period around the menopause , most pronounced in E2 . During the next 3 years , the levels of E2 and E1 showed an essentially parallel , moderate decline . Around the menopause , serum levels of testosterone ( T ) , delta 4- and rostenedione ( A ) and sex hormone-binding globulin ( SHBG ) showed small but significant decreases . From about 3 years postmenopause , the levels were relatively constant over the following 5 years . A decrease in BMD was observed in the postmenopause , and from about 3 years postmenopause , estradiol correlated positively with BMD . Before , as well as after the menopause , body mass index ( BMI ) showed an inverse correlation with SHBG . Postmenopausal and rostenedione correlated positively with E1 , E2 and T. BMI correlated positively with E1 and E2 . The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG , which in turn has a negative correlation with BMI . The impact of this will influence the severity of symptoms , the degree of bone loss and the need for supplementary therapy", "The effect of estrogen and /or and rogen on mood in surgically menopausal women was investigated with a prospect i ve , double-blind , cross-over design . Oophorectomized women who received either estrogen ( E ) , and rogen ( A ) , or a combined estrogen- and rogen preparation ( E-A ) parenterally attained lower depression scores during both treatment phases compared to a placebo group ( PL ) , coincident with their higher plasma estrogen and testosterone levels . When steroids were withdrawn , depression scores of all oophorectomized women were significantly higher than those of a hysterectomized control group with intact ovaries ( CON ) . The A group also had higher hostility scores than the E , PL , and CON groups . These data provide evidence of a covariation between circulating levels of estrogen and testosterone and certain affects in healthy women", "CONTEXT Few studies have examined whether endogenous testosterone is associated with the development of coronary heart disease ( CHD ) in women . OBJECTIVE This study tested the association of total testosterone ( total T ) and bioavailable T ( BioT ) levels with risk of incident coronary events among older community-dwelling women . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , population -based study of 639 postmenopausal women , aged 50 - 91 ( mean , 73.8 ) yr who had serum testosterone measurements at baseline ( 1984 - 87 ) and who were followed for incident CHD events through 2004 . MAIN OUTCOME MEASURES A total of 134 incident CHD events occurred during follow-up [ 45 nonfatal myocardial infa rct ions , 79 fatal myocardial infa rct ions , and 10 coronary revascularizations ] . RESULTS The median follow-up was 12.3 yr . Age-adjusted CHD risk estimates were similar for the four highest total T quintiles relative to the lowest , suggesting a low threshold . In age-adjusted analyses , the lowest total T quintile ( of incident CHD [ 95 % confidence interval ( CI ) , 1.10 - 2.39 ] compared to higher levels . BioT showed a U-shaped association with incident CHD . Age-adjusted risk for the lowest and highest BioT quintiles relative to the third were 1.79 ( 95 % CI , 1.03 - 3.16 ) and 1.96 ( 95 % CI , 1.13 - 3.41 ) , respectively . Additional adjustment for lifestyle , adiposity , estradiol , and ovarian status , or for CHD risk factor covariates , had minimal influence on results . CONCLUSIONS An optimal range of testosterone may exist for cardiovascular health in women , with increased risk of CHD events at low levels of testosterone overall and at high levels of the bioavailable fraction of testosterone", "OBJECTIVE To assess the efficacy and safety of a 300 mug/d testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women on concomitant estrogen therapy . METHODS Five hundred thirty-three women with hypoactive sexual desire disorder who had undergone previous hysterectomy and bilateral oophorectomy were enrolled in a 24-week , multicenter , double-blind , placebo-controlled trial . Patients were r and omly assigned to receive placebo or the testosterone patch twice weekly . The primary efficacy endpoint was change from baseline at week 24 in the frequency of total satisfying sexual activity , measured by the Sexual Activity Log . Secondary measures included sexual desire using the Profile of Female Sexual Function and personal distress as measured by the Personal Distress Scale . Hormone levels , adverse events , and clinical laboratory measures were review ed . RESULTS Total satisfying sexual activity significantly improved in the testosterone patch group compared with placebo after 24 weeks ( mean change from baseline , 1.56 compared with 0.73 episodes per 4 weeks , P = .001 ) . Treatment with the testosterone patch also significantly improved sexual desire ( mean change , 10.57 compared with 4.29 , P personal distress ( P = .009 ) . Serum free , total , and bioavailable testosterone concentrations increased from baseline . Overall , adverse events were similar in both groups ( P > .05 ) . The incidence of and rogenic adverse events was higher in the testosterone group ; most and rogenic adverse events were mild . CONCLUSION In surgically menopausal women with hypoactive sexual desire disorder , a 300 mug/d testosterone patch significantly increased satisfying sexual activity and sexual desire , while decreasing personal distress , and was well tolerated through up to 24 weeks of use", "Objective : Testosterone insufficiency has been associated with psychosexual problems , reduced psychological well-being , and negative metabolic consequences , whereas less is known about the effects on cognition . The aim of this study was to investigate the effect of adding testosterone to estrogen therapy on memory functions in oophorectomized women . Methods : In a r and omized , double-blind , placebo-controlled design , women with surgically induced menopause ( n = 50 ; mean [ SD ] age , 54.0 [ 2.9 ] y ) received estradiol valerate in combination with testosterone undecanoate or placebo . The women were assessed with a self-report question naire regarding memory and neuropsychological tests for verbal and spatial episodic memory and incidental learning at baseline , at the time of crossover , and after completion of treatment . Results : Testosterone undecanoate 40 mg added to estrogen therapy had a negative effect on immediate but not delayed verbal memory at 24 weeks . Subjective and objective memory showed some correspondence as the women in the estrogen + placebo treatment group rated decreased everyday memory problems at 24 weeks compared with baseline . This was not observed in the women in the estrogen + testosterone treatment . Verbal attention span deteriorated from baseline with estrogen + placebo treatment but not with the estrogen + testosterone treatment . However , there was no significant treatment effect between the two groups . Conclusions : Adding testosterone to estrogen treatment deteriorated immediate verbal memory compared with estrogen + placebo , while other memory functions were unaffected" ]

[ "Abstract Twenty-four volunteers ( 19 women and five men ) with insomnia and a history of chronic use of benzodiazepine hypnotics participated in a r and omized , double blind , controlled clinical trial . The study was design ed to assess the effects of substituting zopiclone ( ZOP ) – as an hypnotic – among chronic users of flunitrazepam ( FLU ) , and to compare the subsequent withdrawal of ZOP with placebo controlled withdrawal of FLU . During the 5 weeks of a withdrawal protocol , sleep and physiological parameters were assessed by polysomnographic measures for 11 nights and by nightly actigraphic recordings for weeks 1 , 3 , and 5 . Subjective effects of the withdrawal process were evaluated with daily sleep diaries , and with various weekly self-report symptom checklists . Paired t-tests performed on differences in objective sleep parameters between baseline and the last weeks of the withdrawal program showed a significant decrease in sleep quality within the FLU group , but not in the ZOP group . Subjective sleep diaries consistently reflected the objective ly measured changes in sleep throughout the withdrawal program , indicating significant changes in sleep parameters only in the FLU group . The results obtained from the self report inventories aim ed at assessing withdrawal symptoms , however , revealed no differences between the baseline week and the termination week of the program in any of the groups . After completing the pharmacological withdrawal , all subjects received a short-term cognitive behavioral intervention focused on improving their coping strategies with symptoms of insomnia ; they were evaluated immediately after concluding the intervention , and at 3 and 12 month follow-ups", " Eighty-six participants wishing to stop benzodiazepine and who met DSM-IV ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . American Psychological Association , 1994 ) criteria for anxiety disorder or insomnia were assessed pre- and post-taper on clinical , pharmacological and psychosocial measures . An initial cohort of 41 participants received treatment as usual ( taper only ) plus physician counselling in the same clinic setting . A second cohort of 45 participants were r and omly allocated to group cognitive-behavioural therapy ( CBT ) plus taper , or group support ( GS ) plus taper . At 3 months follow-up , the outcomes in both the CBT and the GS subgroups were equivalent . Intention to treat analysis revealed a slight advantage to the CBT over the GS group and the CBT group showed higher self-efficacy post-taper . Over all 86 participants , a high-baseline level of psychological distress , anxiety and dosage predicted a poor outcome , but increase in self-efficacy contributed to a successful outcome particularly in those with initially poor baseline predictors . Although there was a decrease in positive affect during preliminary stages of tapered discontinuation compared to baseline , there was no significant overall increase in negative affect", "BACKGROUND Benzodiazepines are extensively used in primary care , but their long-term use is associated with adverse health outcomes and dependence . AIMS To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use . METHOD A multicentre three-arm cluster r and omised controlled trial was conducted , with r and omisation at general practitioner level ( trial registration IS RCT N13024375 ) . A total of 532 patients taking benzodiazepines for at least 6 months participated . After all patients were included , general practitioners were r and omly allocated ( 1:1:1 ) to usual care , a structured intervention with follow-up visits ( SIF ) or a structured intervention with written instructions ( SIW ) . The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription cl aims at 12 months . RESULTS At 12 months , 76 of 168 ( 45 % ) patients in the SIW group and 86 of 191 ( 45 % ) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 ( 15 % ) in the control group . After adjusting by cluster , the relative risks for benzodiazepine discontinuation were 3.01 ( 95 % CI 2.03 - 4.46 , P withdrawal symptoms were insomnia , anxiety and irritability . CONCLUSIONS Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity . A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits", "Withdrawal from hypnotics can produce a variety of problems , especially sleep difficulties , some of which may arise from the multiple actions of most hypnotics , thus producing a range of rebound effects . This study examined whether switching patients to a hypnotic with a narrower range of action and of a different class would reduce these problems . One hundred and thirty-four patients participated ; they were r and omly allocated to one of three methods of switching from \" previous hypnotic \" to zopiclone ( a cyclopyrrolone ) . The methods were gap ( an interval between taking the two drugs ) ; abuttal ( taking zopiclone immediately on stopping previous drug ) ; and overlap ( gradually reducing previous drug after starting zopiclone ) . The main findings were that zopiclone was associated with better sleep and increased alertness ; the abuttal method was the best method of switching ; and no serious side effects from zopiclone were reported . It was concluded that zopiclone has a useful role in benzodiazepine withdrawal , and that immediate substitution is the best method", "The Johns Hopkins Precursors Study , a long-term prospect i ve study , was used to study the relation between self-reported sleep disturbances and subsequent clinical depression and psychiatric distress . A total of 1,053 men provided information on sleep habits during medical school at The Johns Hopkins University ( classes of 1948 - 1964 ) and have been followed since graduation . During a median follow-up period of 34 years ( range 1 - 45 ) , 101 men developed clinical depression ( cumulative incidence at 40 years , 12.2 % ) , including 13 suicides . In Cox proportional hazards analysis adjusted for age at graduation , class year , parental history of clinical depression , coffee drinking , and measures of temperament , the relative risk of clinical depression was greater in those who reported insomnia in medical school ( relative risk ( RR ) 2.0 , 95 % confidence interval ( CI ) 1.2 - 3.3 ) compared with those who did not and greater in those with difficulty sleeping under stress in medical school ( RR 1.8 , 95 % CI 1.2 - 2.7 ) compared with those who did not report difficulty . There were weaker associations for those who reported poor quality of sleep ( RR 1.6 , 95 % CI 0.9 - 2.9 ) and sleep duration of 7 hours or less ( RR 1.5 , 95 % CI 0.9 - 2.3 ) with development of clinical depression . Similar associations were observed between reports of sleep disturbances in medical school and psychiatric distress assessed in 1988 by the General Health Question naire . These findings suggest that insomnia in young men is indicative of a greater risk for subsequent clinical depression and psychiatric distress that persists for at least 30 years", "BACKGROUND Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition . AIMS To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice , and to evaluate the value of additional group cognitive-behavioural therapy ( CBT ) . METHOD A 3-month r and omised , 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT , tapering off alone or usual care . RESULTS Tapering off led to a significantly higher proportion of successful discontinuations than usual care ( 62 % nu . 21 % ) . Adding group CBT did not increase the success rate ( 58 % v. 62 % ) . Neither successful discontinuation nor intervention type affected psychological functioning . Both tapering strategies showed good feasibilityin general practice . CONCLUSIONS Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice . The addition of group CBT is of limited value", "Objective A r and omised , controlled clinical trial was performed to study the long-term effect of gradual withdrawal from benzodiazepines on the daily functioning of residents of homes for the elderly . The planned sample size was not achieved due to recruitment and follow-up problems . Results The results in this small sample nevertheless suggest that gradual withdrawal from benzodiazepines is possible in residents of homes for the elderly , and that it can have a positive effect on their daily functioning . No major withdrawal symptoms were observed , although there was a decrease in sleep quality during withdrawal . Conclusion The findings are promising for further research , but research ers should anticipate the problems inherent in executing a trial with institutionalised elderly subjects", "This study aim ed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment ( CBT ) for insomnia . Fifty-three adult chronic users of hypnotics were r and omly assigned to an 8-week hypnotic taper program , used alone or combined with a self-help CBT . Weekly hypnotic use decreased in both conditions , from a nearly nightly use at baseline to less than once a week at posttreatment . Nightly dosage ( in lorazepam equivalent ) decreased from 1.67 mg to 0.12 mg . Participants who received CBT improved their sleep efficiency by 8 % , whereas those who did not remained stable . Total wake time decreased by 52 min among CBT participants and increased by 13 min among those receiving the taper schedule alone . Total sleep time remained stable throughout withdrawal in both CBT and taper conditions . The present findings suggest that a systematic withdrawal schedule might be sufficient in helping chronic users stop their hypnotic medication . The addition of a self-help treatment focusing on insomnia , a readily available and cost-effective alternative to individual psychotherapy , produced greater sleep improvement", "BACKGROUND Older adults are the main recipients of repeat prescriptions for benzodiazepine ( BZD ) hypnotics . BZDs can impair cognitive function and may not aid sleep when taken continuously for years . This study therefore aim ed to determine if withdrawing from BZDs leads to changes in patients ' cognitive function , quality of life , mood and sleep . METHOD One hundred and ninety-two long-term users of BZD hypnotics , aged > or = 65 years , were identified in 25 general practice s. One hundred and four who wished to withdraw were r and omly allocated to one of two groups under double-blind , placebo controlled conditions : group A 's BZD dose was tapered from week 1 of the trial ; group B were given their usual dose for 12 weeks and then it was tapered . An additional group ( C ) of 35 patients who did not wish to withdraw from BZDs participated as ' continuers ' . All patients were assessed at 0 , 12 and 24 weeks and 50 % were reassessed at 52 weeks . RESULTS Sixty per cent of patients had taken BZDs continuously for > 10 years ; 27 % for > 20 years . Of all patients beginning the trial , 80 % had successfully withdrawn 6 months later . There was little difference between groups A and B , but these groups differed from continuers ( C ) in that the performance of the withdrawers on several cognitive/psychomotor tasks showed relative improvements at 24 or 52 weeks . Withdrawers and continuers did not differ in sleep or BZD withdrawal symptoms . CONCLUSIONS These results have clear implication s for clinical practice . Withdrawal from BZDs produces some subtle cognitive advantages for older people , yet little in the way of withdrawal symptoms or emergent sleep difficulties . These findings also suggest that , taken long-term , BZDs do not aid sleep", "CONTEXT Insomnia is a major health problem with significant psychological , health , and economic consequences . However , availability of one of the most effective insomnia treatments , cognitive behavioral therapy , is significantly limited . The Internet may be a key conduit for delivering this intervention . OBJECTIVE To evaluate the efficacy of a structured behavioral Internet intervention for adults with insomnia . DESIGN , SETTING , AND PARTICIPANTS Forty-five adults were r and omly assigned to an Internet intervention ( n = 22 ) or wait-list control group ( n = 23 ) . Forty-four eligible participants ( mean [ SD ] age , 44.86 [ 11.03 ] years ; 34 women ) who had a history of sleep difficulties longer than 10 years on average ( mean [ SD ] , 10.59 [ 8.89 ] years ) were included in the analyses . INTERVENTION The Internet intervention is based on well-established face-to-face cognitive behavioral therapy incorporating the primary components of sleep restriction , stimulus control , sleep hygiene , cognitive restructuring , and relapse prevention . MAIN OUTCOME MEASURES The Insomnia Severity Index and daily sleep diary data were used to determine changes in insomnia severity and the main sleep variables , including wake after sleep onset and sleep efficiency . RESULTS Intention-to-treat analyses showed that scores on the Insomnia Severity Index significantly improved from 15.73 ( 95 % confidence interval [ CI ] , 14.07 to 17.39 ) to 6.59 ( 95 % CI , 4.73 to 8.45 ) for the Internet group but did not change for the control group ( 16.27 [ 95 % CI , 14.61 to 17.94 ] to 15.50 [ 95 % CI , 13.64 to 17.36 ] ) ( F(1,42 ) = 29.64 ; P wake after sleep onset ( 55 % [ 95 % CI , 34 % to 76 % ] ) and increases in sleep efficiency ( 16 % [ 95 % CI , 9 % to 22 % ] ) compared with the nonsignificant control group changes of wake after sleep onset ( 8 % [ 95 % CI , -17 % to 33 % ) and sleep efficiency ( 3 % ; 95 % CI , -4 % to 9 % ) . CONCLUSIONS Participants who received the Internet intervention for insomnia significantly improved their sleep , whereas the control group did not have a significant change . The Internet appears to have considerable potential in delivering a structured behavioral program for insomnia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00328250", "BACKGROUND Benzodiazepines are the most frequently used drug for the treatment of insomnia . Prolonged use of benzodiazepine therapy is not recommended . However , many patients , particularly older patients , have difficulties discontinuing therapy . Melatonin , a hormone that is produced at night by the pineal gl and , promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy . OBJECTIVE To assess whether the administration of melatonin could facilitate the discontinuation of benzodiazepine therapy in patients with insomnia . METHODS Thirty-four subjects receiving benzodiazepine therapy were enrolled in the 2-period study . In period 1 , patients received ( double-blinded ) melatonin ( 2 mg in a controlled-release formulation ) or a placebo nightly for 6 weeks . They were encouraged to reduce their benzodiazepine dosage 50 % during week 2 , 75 % during weeks 3 and 4 , and to discontinue benzodiazepine therapy completely during weeks 5 and 6 . In period 2 , melatonin was administered ( single-blinded ) for 6 weeks to all subjects and attempts to discontinue benzodiazepine therapy were resumed . Benzodiazepine consumption and subjective sleep- quality scores were reported daily by all patients . All subjects were then allowed to continue melatonin therapy and follow-up re assessment s were performed 6 months later . RESULTS By the end of period 1 , 14 of 18 subjects who had received melatonin therapy , but only 4 of 16 in the placebo group , discontinued benzodiazepine therapy ( P = .006 ) . Sleep- quality scores were significantly higher in the melatonin therapy group ( P = .04 ) . Six additional subjects in the placebo group discontinued benzodiazepine therapy when given melatonin in period 2 . The 6-month follow-up assessment s revealed that of the 24 patients who discontinued benzodiazepine and received melatonin therapy , 19 maintained good sleep quality . CONCLUSION Controlled-release melatonin may effectively facilitate discontinuation of benzodiazepine therapy while maintaining good sleep quality", "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", "We compared the effect of abrupt discontinuation of therapeutic doses of short half-life and long half-life benzodiazepines in 57 benzodiazepine-dependent patients ( daily use , greater than 1 year ) . Despite the use of a mean daily dose of 14.1 mg of diazepam equivalents , there were notable residual symptoms of anxiety and depression present at intake ( Hamilton Rating Scale for Anxiety score , 17.0 ; Hamilton Rating Scale for Depression score , 14.0 ) . Benzodiazepine intake was stabilized for 3 weeks before double-blind assignment to placebo ( n = 47 ) , or continued benzodiazepine use ( n = 10 ) . Clinical assessment s were performed daily , including benzodiazepine plasma levels . Depending on the outcome criteria used , anywhere from 58 % to 100 % of patients were judged to have experienced a withdrawal reaction , with a peak severity at 2 days for short half-life and 4 to 7 days for long half-life benzodiazepines . Relapse onto benzodiazepines occurred in 27 % of patients who were receiving long half-life benzodiazepines and in 57 % of patients who were receiving short half-life benzodiazepines . Baseline predictors of relapse were nonpanic diagnoses , a higher benzodiazepine dose , and a higher Eysenck neuroticism score . A short half-life and higher daily doses were associated with greater withdrawal severity , as were personality traits , such as dependency and neuroticism , less education and higher baseline levels of anxious and depressive symptoms . Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation . These results provide a detailed picture of the symptoms , time course , and multidimensional determinants of the benzodiazepine withdrawal syndrome", "BACKGROUND Long-term use of hypnotics is not recommended because of risks of dependency and adverse effects on health . The usual clinical management of benzodiazepine dependency is gradual tapering , but when used alone this method is not highly effective in achieving long-term discontinuation . We compared the efficacy of tapering plus cognitive-behavioural therapy for insomnia with tapering alone in reducing the use of hypnotics by older adults with insomnia . METHODS People with chronic insomnia who had been taking a benzodiazepine every night for more than 3 months were recruited through media advertisements or were referred by their family doctors . They were r and omly assigned to undergo either cognitive-behavioural therapy plus gradual tapering of the drug ( combined treatment ) or gradual tapering only . The cognitive-behavioural therapy was provided by a psychologist in 8 weekly small-group sessions . The tapering was supervised by a physician , who met weekly with each participant over an 8-week period . The main outcome measure was benzodiazepine discontinuation , confirmed by blood screening performed at each of 3 measurement points ( immediately after completion of treatment and at 3- and 12-month follow-ups ) . RESULTS Of the 344 potential participants , 65 ( mean age 67.4 years ) met the inclusion criteria and entered the study . The 2 study groups ( 35 subjects in the combined treatment group and 30 in the tapering group ) were similar in terms of demographic characteristics , duration of insomnia and hypnotic dosage . Immediately after completion of treatment , a greater proportion of patients in the combined treatment group had withdrawn from benzodiazepine use completely ( 77 % [ 26/34 ] v. 38 % [ 11/29 ] ; odds ratio [ OR ] 5.3 , 95 % confidence interval [ CI ] 1.8 - 16.2 ; OR after adjustment for initial benzodiazepine daily dose 7.9 , 95 % CI 2.4 - 30.9 ) . At the 12-month follow-up , the favourable outcome persisted ( 70 % [ 23/33 ] v. 24 % [ 7/29 ] ; OR 7.2 , 95 % CI 2.4 - 23.7 ; adjusted OR 7.6 , 95 % CI 2.5 - 26.6 ) ; similar results were obtained at 3 months . INTERPRETATION A combination of cognitive-behavioural therapy and benzodiazepine tapering was superior to tapering alone in the management of patients with insomnia and chronic benzodiazepine use . The beneficial effects were sustained for up to 1 year . Applying this multidisciplinary approach in the community could help reduce benzodiazepine use by older people", "We compared the effect on withdrawal severity and acute outcome of a 25 % per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients . Patients unable to tolerate taper were permitted to slow the taper rate . Ninety percent of patients experienced a withdrawal reaction , but it was rarely more than mild to moderate . Nonetheless , 32 % of long half-life and 42 % of short half-life benzodiazepine-treated patients were unable to achieve a drug-free state . The most difficulty was experienced in the last half of taper . Baseline personality , high Eysenck neuroticism , female sex , and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life . These findings suggest that personality factors contribute significantly to the patient 's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines", "Objective : To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial . Method : We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition , r and omized , controlled benzodiazepine discontinuation trial in general practice . Results : Of 180 patients , we completed follow-up for 170 ( 94 % ) . Of these , 50 ( 29 % ) achieved long-term success , defined as no use of benzodiazepines during follow-up . Independent predictors of success were as follows : offering a taper-off program with group therapy ( hazard ratio [ HR ] 2.4 ; 95 % confidence interval [ CI ] , 1.5 to 3.9 ) or without group therapy ( HR 2.9 ; 95%CI , 1.8 to 4.8 ) ; a lower daily benzodiazepine dosage at the start of tapering off ( HR 1.5 ; 95%CI , 1.2 to 1.9 ) ; a substantial dosage reduction by patients themselves just before the start of tapering off ( HR 2.1 ; 95%CI , 1.4 to 3.3 ) ; less severe benzodiazepine dependence , as measured by the Benzodiazepine Dependence Self-Report Question naire Lack of Compliance subscale ( HR 2.4 ; 95%CI , 1.1 to 5.2 ) ; and no use of alcohol ( HR 1.7 ; 95%CI , 1.2 to 2.5 ) . Patients who used over 10 mg of diazepam equivalent , who had a score of 3 or more on the Lack of Compliance subscale , or who drank more than 2 units of alcohol daily failed to achieve long-term abstinence . Conclusions : Benzodiazepine dependence severity affects long-term taper outcome independent of treatment modality , benzodiazepine dosage , psychopathology , and personality characteristics . An identifiable subgroup needs referral to specialized care", "OBJECTIVE This study evaluated the effectiveness of a supervised benzodiazepine taper , singly and combined with cognitive behavior therapy , for benzodiazepine discontinuation in older adults with chronic insomnia . METHOD Seventy-six older adult out patients ( 38 women , 38 men ; mean age of 62.5 years ) with chronic insomnia and prolonged use ( mean duration of 19.3 years ) of benzodiazepine medication for sleep were r and omly assigned for a 10-week intervention consisting of a supervised benzodiazepine withdrawal program ( N=25 ) , cognitive behavior therapy for insomnia ( N=24 ) , or supervised withdrawal plus cognitive behavior therapy ( N=27 ) . Follow-up assessment s were conducted at 3 and 12 months . The main outcome measures were benzodiazepine use , sleep parameters , and anxiety and depressive symptoms . RESULTS All three interventions produced significant reductions in both the quantity ( 90 % reduction ) and frequency ( 80 % reduction ) of benzodiazepine use , and 63 % of the patients were drug-free within an average of 7 weeks . More patients who received medication taper plus cognitive behavior therapy ( 85 % ) were benzodiazepine-free after the initial intervention , compared to those who received medication taper alone ( 48 % ) and cognitive behavior therapy alone ( 54 % ) . The patients in the two groups that received cognitive behavior therapy perceived greater subjective sleep improvements than those who received medication taper alone . Polysomnographic data showed an increase in the amount of time spent in stages 3 and 4 sleep and REM sleep and a decrease in total sleep time across all three conditions from baseline to posttreatment . Initial benzodiazepine reductions were well maintained up to the 12-month follow-up , and sleep improvements became more noticeable over this period . No significant withdrawal symptoms or adverse events were associated with benzodiazepine tapering . CONCLUSIONS A structured , time-limited intervention is effective in assisting chronic users of benzodiazepine medication to discontinue or reduce their use of medication . The addition of cognitive behavior therapy alleviates insomnia , but sleep improvements may become noticeable only after several months of benzodiazepine abstinence", "We conducted a double-blind , placebo-controlled trail in which 40 patients who had undergone long-term therapy with benzodiazepines were switched to placebo or to diazepam in a dose approximately equivalent to their usual dose of the benzodiazepine ; the dose of diazepam was then tapered during an eight-week period . Patients were assessed clinical ly and psychologically and had weekly sessions of behavioral therapy . The subjects who received placebo had more symptoms , assessed their symptoms as more severe , and stopped taking the study drug at a higher rate than those receiving the tapering doses of diazepam . The subjects in the placebo group also had symptoms shortly after being switched to placebo , whereas those in the diazepam group had symptoms much later . Some withdrawal symptoms were distinct from those of anxiety ( e.g. , tinnitus , involuntary movement , and perceptual changes ) . Withdrawal symptoms occurred earlier in patients who had received short-acting benzodiazepines than in those who had received long-acting benzodiazepines . Symptoms gradually disappeared over a four-week period in both the placebo and the diazepam groups . Serial determination of plasma benzodiazepine concentrations was a useful way to assess compliance , treatment outcome , and relapse during withdrawal . We conclude that a clinical ly important , mild , but distinct withdrawal syndrome occurs after discontinuation of long-term therapeutic use of benzodiazepines", "DESCRIPTION The American College of Physicians ( ACP ) developed this guideline to present the evidence and provide clinical recommendations on the management of chronic insomnia disorder in adults . METHODS This guideline is based on a systematic review of r and omized , controlled trials published in English from 2004 through September 2015 . Evaluated outcomes included global outcomes assessed by question naires , patient-reported sleep outcomes , and harms . The target audience for this guideline includes all clinicians , and the target patient population includes adults with chronic insomnia disorder . This guideline grade s the evidence and recommendations by using the ACP grading system , which is based on the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) approach . RECOMMENDATION 1 ACP recommends that all adult patients receive cognitive behavioral therapy for insomnia ( CBT-I ) as the initial treatment for chronic insomnia disorder . ( Grade : strong recommendation , moderate- quality evidence ) . RECOMMENDATION 2 ACP recommends that clinicians use a shared decision-making approach , including a discussion of the benefits , harms , and costs of short-term use of medications , to decide whether to add pharmacological therapy in adults with chronic insomnia disorder in whom cognitive behavioral therapy for insomnia ( CBT-I ) alone was unsuccessful . ( Grade : weak recommendation , low- quality evidence )" ]

[ "BACKGROUND Depression is common and the efficacy of antidepressants is suboptimal . High plasma homocysteine has been consistently associated with depression , and treatment with certain B vitamins demonstrably reduces its concentration . AIMS To determine whether vitamins B6 , B12 and folic acid enhance response to antidepressant treatment over 52 weeks . METHOD R and omised , double-blind , placebo-controlled trial of citalopram ( 20 - 40 g ) together with 0.5 mg of vitamin B12 , 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks ( Australian and New Zeal and Clinical Trials Registry : 12609000256279 ) . Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression . We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The primary outcome was remission of the depressive episode after 12 , 26 and 52 weeks . Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12 . Results In total , 153 people were r and omised ( 76 placebo , 77 vitamins ) . Remission of symptoms was achieved by 78.1 and 79.4 % of participants treated with placebo and vitamins by week 12 ( P = 0.840 ) , by 76.5 and 85.3 % at week 26 and 75.8 and 85.5 % at week 52 ( effect of intervention over 52 weeks : odds ratio ( OR ) = 2.49 , 95 % CI 1.12 - 5.51 ) . Group differences in MADRS scores over time were not significant ( P = 0.739 ) . The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group ( OR = 0.33 , 95 % CI 0.12 - 0.94 ) . CONCLUSIONS B vitamins did not increase the 12-week efficacy of antidepressant treatment , but enhanced and sustained antidepressant response over 1 year . Replication of these findings would m and ate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults ", "BACKGROUND B-vitamin deficiencies have been associated with depression ; however , there is very little prospect i ve evidence from population -based studies of older adults . OBJECTIVE We examined whether dietary intakes of vitamins B-6 , folate , or vitamin B-12 were predictive of depressive symptoms over an average of 7.2 y in a community-based population of older adults . DESIGN The study sample consisted of 3503 adults from the Chicago Health and Aging project , an ongoing , population -based , biracial ( 59 % African American ) study in adults aged > or = 65 y. Dietary assessment was made by food-frequency question naire . Incident depression was measured by the presence of > or = 4 depressive symptoms from the 10-item version of the Center for Epidemiologic Studies Depression scale . RESULTS The logistic regression models , which used generalized estimating equations , showed that higher total intakes , which included supplementation , of vitamins B-6 and B-12 were associated with a decreased likelihood of incident depression for up to 12 y of follow-up , after adjustment for age , sex , race , education , income , and antidepressant medication use . For example , each 10 additional milligrams of vitamin B-6 and 10 additional micrograms of vitamin B-12 were associated with 2 % lower odds of depressive symptoms per year . There was no association between depressive symptoms and food intakes of these vitamins or folate . These associations remained after adjustment for smoking , alcohol use , widowhood , caregiving status , cognitive function , physical disability , and medical conditions . CONCLUSION Our results support the hypotheses that high total intakes of vitamins B-6 and B-12 are protective of depressive symptoms over time in community-residing older adults", "BACKGROUND The role of folate , vitamin B(12 ) and homocysteine levels in depression is not clear . AIMS To investigate cross-sectional and prospect i ve associations between folate , B(12 ) and homocysteine levels and late-life depression . METHOD A total of 732 Korean people aged 65 years or over were evaluated at baseline . Of the 631 persons who were not depressed , 521 ( 83 % ) were followed over a period of 2 - 3 years and incident depression was ascertained with the Geriatric Mental State schedule . Serum folate , serum vitamin B(12 ) and plasma homocysteine levels were assayed at both baseline and follow-up . RESULTS Lower levels of folate and vitamin B(12 ) and higher homocysteine levels at baseline were associated with a higher risk of incident depression at follow-up . Incident depression was associated with a decline in vitamin B(12 ) and an increase in homocysteine levels over the follow-up period . CONCLUSIONS Lower folate , lower vitamin B(12 ) and raised homocysteine levels may be risk factors for late-life depression ", "Objectives : 1 ) To compare serum vitamin B12 , C and folate concentrations in a r and omly selected sample of elderly ( age 65 years or older ) male and female Hispanics and nonHispanic whites ( NHW ) and 2 ) to examine associations between serum B12 , C and folate concentrations compared to measures of cognitive and affective ( depression ) functions . Methods : Equal numbers of male and female Hispanics and NHW were r and omly sample d from the Health Care Financing Administration ( Medicare ) registrant list for Bernalillo County , New Mexico , and asked to volunteer for a paid home interview followed by a paid comprehensive interview/examination covering health and health-related issues . In addition to serum determinations of B12 , C and folate , associations were examined between these vitamins and measures of cognitive and affective functions . Results : Males and Hispanics had lower serum vitamin B12 , C and folate concentrations than females and NHW respectively . Participants taking a multivitamin supplement ( MVI ) had higher serum vitamin concentrations than those not taking MVI . There were significant associations between serum folate concentrations and measures of cognitive function , not seen with B12 or C , nor between any of the vitamins and affective function . Conclusions : Hispanics , even after adjustments for gender , age , vitamin supplementation , vitamin content of dietary foods , education and household income , had lower serum concentrations of B12 , C and folate than NHW . The most significant associations observed were those between serum folate and various measures of cognitive function , even after adjusting for presence of depression", "OBJECTIVE The associations of vitamin B(12 ) , folate , and homocysteine with depression were examined in a population -based study . METHOD The authors screened 3,884 elderly people for depressive symptoms . Subjects with positive screening results had psychiatric workups . Folate , vitamin B(12 ) , and homocysteine blood levels were compared in 278 persons with depressive symptoms , including 112 with depressive disorders , and 416 r and omly selected reference subjects . Adjustments were made for age , gender , cardiovascular disease , and functional disability . RESULTS Hyperhomocysteinemia , vitamin B(12 ) deficiency , and to a lesser extent , folate deficiency were all related to depressive disorders . For folate deficiency and hyperhomocysteinemia , the association with depressive disorders was substantially reduced after adjustment for functional disability and cardiovascular disease , but for vitamin B(12 ) this appeared independent . CONCLUSIONS The association of vitamin B(12 ) and folate with depressive disorders may have different underlying mechanisms . Vitamin B(12 ) may be causally related to depression , whereas the relation with folate is due to physical comorbidity", "OBJECTIVE The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors ( SSRIs ) . METHOD In the first trial , 148 out patients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods . Patients were r and omly assigned , in a 2:3:3 ratio , to receive L-methylfolate for 60 days ( 7.5 mg/day for 30 days followed by 15 mg/day for 30 days ) , placebo for 30 days followed by L-methylfolate ( 7.5 mg/day ) for 30 days , or placebo for 60 days . SSRI dosages were kept constant throughout the study . In the second trial , with 75 patients , the design was identical to the first , except that the l-methylfolate dosage was 15 mg/day during both 30-day periods . RESULTS In the first trial , no significant difference was observed in outcomes between the treatment groups . In the second trial , adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy compared with continued SSRI therapy plus placebo on both primary outcome measures ( response rate and degree of change in depression symptom score ) and two secondary outcome measures of symptom severity . The number needed to treat for response was approximately six in favor of adjunctive L-methylfolate at 15 mg/day . L-Methylfolate was well tolerated , with rates of adverse events no different from those reported with placebo . CONCLUSIONS Adjunctive L-methylfolate at 15 mg/day may constitute an effective , safe , and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs", "Depressed geriatric patients have lower levels of folate ( FOL ) than controls . Also , FOL supplement can reduce depressive morbidity . One hypothesis consistent with this is that FOL deficiency causes a lowering of CNS serotonin that contributes to depression . The present report is from one site of a multicenter study that compared an SSRI ( sertraline ) with a nonspecific tricyclic antidepressant ( nortriptyline ) in geriatric depressed patients . We added measures of FOL at baseline and outcome for 22 depressed patients older than 60 years . Both treatments were effective . At baseline , FOL levels were within the normal range . Higher FOL levels at baseline predicted greater improvement . Further study of FOL interaction with SSRI is warranted . For the group treated with the SSRI , baseline FOL level was a more efficient predictor of improvement , especially for results on a self-rating depression scale ( POMS )", "Tetrahydrobiopterin is a cofactor in the synthesis of monoamine neurotransmitters . High neopterin levels generally signal increased immune activation . Both pterins have been investigated in several small clinical studies of depressed patients with conflicting results . Therefore , we examined the relation of plasma biopterin and neopterin with depression in a population -based study . We also studied the association of pterins with folates in depressed persons as this vitamin is required for pterin bio synthesis . We screened 3884 adults aged 60 years and over for depressive symptoms . Screen positive subjects had a psychiatric interview to diagnose DSM-IV disorder . Plasma pterins and serum folate were determined in all persons with depressive symptoms ( n=238 ) and r and omly selected non-depressed persons ( n=357 ) . We found no association between the concentration of biopterin or neopterin with depressive symptoms or depressive disorders . However , in depressed persons the relation between pterins and folates was different than in the non-depressed , i.e. neopterin concentrations increased with folate levels in persons with depressive symptoms ( 0.09 per log(nmol/l folate ) ; 95 % CI=0.01 , 0.18 , P=0.03 ) , but not in non-depressed persons ( -0.07 per log(nmol/l folate ) ; 95 % CI=-0.17 , 0.03 , P=0.18 ) . The interaction between depressive symptoms , folate and neopterin was significant ( P=0.03 ) . The study suggests that the relation between folate and pterins is altered in the depressed elderly", "5-methyltetrahydrofolate ( MTHF ) is a naturally occurring substance involved in the synthesis of s-adenosyl-l-methionine ( SAMe ) , a major source of methyl groups in the brain . To assess the efficacy of a gastro-resistant , oral preparation of MTHF , 20 elderly patients with a DSM-III-R diagnosis of depressive disorder and a HAM-D-21 score > or = 18 underwent 6-weeks of open-label treatment with 50 mg per day of oral MTHF . Of these 20 patients , 16 completed at least 4 weeks of treatment and showed a markedly significant improvement in their depressive symptoms at endpoint , with 81 % of them being considered responders . There were no clinical ly relevant changes in the routine laboratory tests during the study , and no adverse events considered to be definitely drug-related were reported", "This was a 4-week r and omized placebo-controlled double-blind study to assess augmentation of open tricyclic antidepressant treatment with 10 mg each of vitamins B1 , B2 , and B6 in 14 geriatric in patients with depression . The active vitamin group demonstrated significantly better B2 and B6 status on enzyme activity coefficients and trends toward greater improvement in scores on ratings of depression and congnitive function , as well as in serum nortriptyline levels compared with placebo-treated subjects ( Ss ) . Without specific supplementation , B12 levels increased in Ss receiving B1/B2/B6 and decreased in placebo Ss . These findings offer preliminary support for further investigation of B complex vitamin augmentation in the treatment of geriatric depression", "OBJECTIVE In the present study , we assessed the relationship between serum folate , vitamin B12 , and homocysteine levels and clinical response in patients with major depressive disorder ( MDD ) who had previously failed to respond to open treatment with fluoxetine 20 mg/day and were enrolled in a 4-week , double-blind trial of either ( 1 ) fluoxetine dose increase , ( 2 ) lithium augmentation of fluoxetine , or ( 3 ) desipramine augmentation of fluoxetine . METHOD Fifty-five out patients ( mean + /- SD age = 41.7 + /- 10.6 years ; 50.9 % women ) with MDD as assessed with the Structured Clinical Interview for DSM-III-R who were enrolled in the double-blind trial had serum folate , vitamin B12 , and homocysteine measurements completed at baseline ( prior to fluoxetine treatment initiation ) . Folate levels were classified as either low ( Vitamin B12 levels were classified as either low ( Homocysteine levels were classified as either elevated ( > or = 13.2 micromol/L ) or normal . With the use of a logistic regression , we then assessed the relationship between ( 1 ) low or normal folate levels , ( 2 ) normal or low B12 levels , and ( 3 ) elevated or normal homocysteine levels and clinical response to double-blind treatment . The study was conducted from November 1992 to January 1999 . RESULTS Low serum folate levels ( chi2=3.626 , p = .04 ) , but not elevated homocysteine ( p > .05 ) or low vitamin B12 levels ( p > .05 ) , were associated with poorer response to treatment . The response rates for patients with ( N = 14 ) and without ( N = 38 ) low folate levels were 7.1 % versus 44.7 % , respectively . CONCLUSION Low serum folate levels were found to be associated with further treatment resistance among patients with fluoxetine-resistant MDD", "BACKGROUND Folate deficiency is associated with depression . Despite the biological plausibility of a causal link , the evidence that adding folate enhances antidepressant treatment is weak . OBJECTIVES ( 1 ) Estimate the clinical effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant medication ( ADM ) . ( 2 ) Explore whether baseline folate and homocysteine predict response to treatment . ( 3 ) Investigate whether response to treatment depends on genetic polymorphisms related to folate metabolism . DESIGN FolATED ( Folate Augmentation of Treatment - Evaluation for Depression ) was a double-blind and placebo-controlled , but otherwise pragmatic , r and omised trial including cost-utility analysis . To yield 80 % power of detecting st and ardised difference on the Beck Depression Inventory version 2 ( BDI-II ) of 0.3 between groups ( a ' small ' effect ) , FolATED trialists sought to analyse 358 participants . To allow for an estimated loss of 21 % of participants over three time points , we planned to r and omise 453 . SETTING S Clinical - Three centres in Wales - North East Wales , North West Wales and Swansea . Trial management - North Wales Organisation for R and omised Trials in Health in Bangor University . Biochemical analysis - University Hospital of Wales , Cardiff . Genetic analysis - University of Liverpool . PARTICIPANTS Four hundred and seventy-five adult patients presenting to primary or secondary care with confirmed moderate to severe depression for which they were taking or about to start ADM , and able to consent and complete assessment s , but not ( 1 ) folate deficient , vitamin B12 deficient , or taking folic acid or anticonvulsants ; ( 2 ) misusing drugs or alcohol , or suffering from psychosis , bipolar disorder , malignancy or other unstable or terminal illness ; ( 3 ) ( planning to become ) pregnant ; or ( 4 ) participating in other clinical research . INTERVENTIONS Once a day for 12 weeks experimental participants added 5 mg of folic acid to their ADM , and control participants added an indistinguishable placebo . All participants followed pragmatic management plans initiated by a trial psychiatrist and maintained by their general medical practitioners . MAIN OUTCOME MEASURES Assessed at baseline , and 4 , 12 and 25 weeks thereafter , and analysed by ' area under curve ' ( main ) ; by analysis of covariance at each time point ( secondary ) ; and by multi-level repeated measures ( sensitivity analysis ): Mental health - BDI-II ( primary ) , Clinical Global Impression ( CGI ) , Montgomery-Åsberg Depression Rating Scale ( MADRS ) , UKU side effects scale , and Mini International Neuropsychiatric Interview ( MINI ) suicidality subscale ; General health - UK 12-item Short Form Health Survey ( SF-12 ) , European Quality of Life scale - 5 Dimensions ( EQ-5D ) ; Biochemistry - serum folate , B12 , homocysteine ; Adherence - Morisky Question naire ; Economics - re source use . RESULTS Folic acid did not significantly improve any of these measures . For example it gained a mean of just 2.9 quality -adjusted life-days [ 95 % confidence interval ( CI ) from -12.7 to 7.0 days ] and saved a mean of just £ 48 ( 95 % CI from -£292 to £ 389 ) . In contrast it significantly reduced mental health scores on the SF-12 by 3.0 % ( 95 % CI from -5.2 % to -0.8 % ) . CONCLUSIONS The FolATED trial generated no evidence that folic acid was clinical ly effective or cost-effective in augmenting ADM . This negative finding is consistent with improving underst and ing of the one-carbon folate pathway suggesting that methylfolate is a better c and i date for augmenting ADM . Hence the findings of FolATED undermine treatment guidelines that advocate folic acid for treating depression , and suggest future trials of methylfolate to augment ADM . TRIAL REGISTRATION Current Controlled Trials IS RCT N37558856 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 18 , No. 48 . See the HTA programme website for further project information" ]

[ "Background Open-label quetiapine coadministration with SSRI therapy , in a diagnostically mixed sample of comorbid anxiety patients , offered additional anxiolytic benefit . Therefore , we design ed the following controlled trial to confirm these findings in a comorbid , SSRI-resistant , panic disorder ( PD ) patient sample . Methods This was a single-site , double-blind , placebo-controlled ( PLAC ) , r and omized , parallel group ( 2 groups ) , 8-week , quetiapine extended release ( XR ) coadministration trial . SSRI resistance was determined either historically or prospect ively . Patients were r and omized if they remained moderately ill ( CGI-S score ≥ 4 ) . Change in the PDSS scale total score was the primary efficacy outcome measure . Responders were identified as those with a ≥50 % decrease from their baseline PDSS score . In the early weeks of therapy , XR was flexibly and gradually titrated from 50 to 400 mg/day . Results 43 patients were screened in total , and 26 of these were r and omized and evaluable . 21 patients ( 78 % of the r and omized group ) completed the trial ( 10 XR ; 11 PLAC ) . The endpoint quetiapine XR mean daily dose ± SD was 150 ± 106 mg . While , in the sample as a whole , there was improvement in PDSS scores across the 8-week trial ( ANOVA main effect of time , F = 10.9 , df8,192 , p . Quetiapine XR was generally well-tolerated . Important limitations were the small sample size , and the relatively low average dose of quetiapine XR used . Clinical Trials.gov ID # :", "Abstract This long-term extension of an 8-week r and omized , naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam ( n = 47 ) and paroxetine ( n = 37 ) over a 3-year total treatment duration . Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine ( both taken at bedtime ) . This study reports data from the long-term period ( 34 months ) , following the initial 8-week treatment phase . Thus , total treatment duration was 36 months . Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine , but patients with partial primary treatment success were switched to the combination therapy . At initiation of the long-term study , the mean doses of clonazepam and paroxetine were 1.9 ( SD , 0.30 ) and 38.4 ( SD , 3.74 ) mg/d , respectively . These doses were maintained until month 36 ( clonazepam 1.9 [ SD , 0.29 ] mg/d and paroxetine 38.2 [ SD , 3.87 ] mg/d ) . Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine ( mean difference : CGI-Severity scale −3.48 vs −3.24 , respectively , P = 0.02 ; CGI-Improvement scale 1.06 vs 1.11 , respectively , P = 0.04 ) . Both treatments similarly reduced the number of panic attacks and severity of anxiety . Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine ( 28.9 % vs 70.6 % , P efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course . There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events", "Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies . This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder . Patients who satisfactorily completed a 12-week , double-blind , placebo-controlled study of paroxetine and clomipramine could choose to continue receiving their r and omized treatment for a further 36 weeks . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression Scale , the Hamilton Anxiety Rating Scale , the Marks Sheehan Phobia Scale and the Sheehan Disability Scale . In total , 176 patients were included in the intention-to-treat population . The number of full panic attacks decreased in all three groups during the 12-week study , and improvements continued with long-term therapy . Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks , and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks . There were no significant differences between paroxetine and clomipramine . The proportion of patients who withdrew from the study due to adverse effects was greater in the clomipramine group ( 19 % ) than in either the paroxetine group ( 7 % ) or the placebo group ( 9 % ) . Paroxetine was significantly more effective than placebo and as effective as ( but better tolerated than ) clomipramine in the long-term treatment of panic disorder . Not only was efficacy maintained , but continued improvement was also seen , indicating the importance of long-term treatment in patients with panic disorder", "Non-response to pharmacotherapy for panic disorder ( PD ) is a well-documented problem . However , little information exists to guide next-step strategies for these non-responders . In addition to pharmacologic augmentation strategies , several studies support the efficacy of cognitive-behavior therapy ( CBT ) for these patients , although data on long-term outcomes has been lacking . In this study , we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy . Sustained significant benefit was found for all dimensional outcome scores , and nearly two-thirds of the sample met remission criteria . This occurred with reductions in medication use over the follow-up period . Negative predictors of remission status included comorbid dysthymia , social phobia , and generalized anxiety disorder . These results provide additional evidence for the efficacy of CBT for medication non-responders with PD", "Agoraphobia in panic disorder ( PD ) has been related to abnormal balance system function . Vision influences balance and behavioural adaptations ; peripheral vision influences orienting and fast defensive reactions whereas central vision analyzes details of objects . We have hypothesized that the abnormal balance function in PD could be mainly related to peripheral vision as part of a defensive alarm system in the brain . In 25 patients with PD and agoraphobia and 31 healthy controls we assessed , by posturography , balance system reactivity to video-films projected in peripheral and central visual fields ( r and omized sequence ) . Length , velocity and surface of body sway were calculated . Patients increased their body sway during peripheral stimulation , whereas controls did not ; the two groups showed a similar increase of body sway during central stimulation . Anxiety levels during peripheral stimulation significantly influenced the postural response in the group of patients . These preliminary results suggest that the higher visual sensitivity to peripheral stimulation in patients with PD and agoraphobia may be linked to a more active \" visual alarm system \" involving visual , vestibular and limbic areas that might influence the development of agoraphobia in situations where environmental stimuli are uncertain", "Experimental evidence suggests that panic disorder is characterized by abnormalities in the balance system function and that these abnormalities might be related to the severity of agoraphobic avoidance . Since the balance system can be modulated by the serotonergic system , we investigated the effect of a 6‐week treatment with citalopram on the balance system function in patients with panic disorder . Fifteen patients with panic disorder with/without agoraphobia underwent static posturography on days 0 and 42 . Static posturography and clinical assessment s were carried out by different investigators who were blind to each other . Static posturography showed high percentages of abnormal scores . Patients with no or low agoraphobic avoidance showed less abnormal posturographic measures than those with moderate to severe agoraphobia . After 6 weeks of treatment with citalopram there was a significant decrease of four out of six posturography measures in eyes‐closed and neck extension conditions , whereas no significant effect was found in the eyes‐open condition . This is the first report that suggests that the modulation of the serotonergic system can improve the balance system function in patients with panic disorder , particularly when visual information is lacking . In addition , our findings confirm the observation that many patients with panic disorder have abnormalities in their balance system function , supporting the idea that these abnormalities are mainly related to agoraphobic avoidance . Depression and Anxiety 17:101–106 , 2003 . © 2003 Wiley‐Liss ,", "INTRODUCTION Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder ( PD ) . However preliminary studies suggested that reboxetine might be effective in the treatment of PD . We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD . METHODS Sixty-eight patients with PD were assigned to treatment groups in a single-blind , r and omized design . Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Side effects were also recorded . RESULTS Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one . Vice versa we did not find any significant differences for other outcome measures . Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group . CONCLUSIONS The results showed a greater effect of paroxetine on panic attacks than reboxetine , while no differences for anticipatory anxiety and avoidance were found , suggesting a different role of noradrenaline and serotonin in the treatment of PD", "Abstract : The effects of short treatments ( 7 days ) with paroxetine and with reboxetine on the reactivity to inhalations of 35 % carbon dioxide (CO2)/65 % oxygen ( O2 ) were compared in 28 patients with Panic Disorder who had positive responses to 35 % CO2 inhalations . A double-blind , r and omized design was applied . Each patient was given the 35 % CO2 challenge on days 0 ( before starting the treatment ) and 7 . Anxiety reactivity to CO2 decreased significantly with both drugs but the decrease was significantly stronger in the group treated with paroxetine . The rate of patients whose reactivity has reduced of at least 50 % after 7 days was significantly higher in the group treated with paroxetine ( 10/14 , 71.5 % ) than in the one treated with reboxetine ( 3/14 , 21.5 % ) . These results indicate that the modulation of the serotonergic system is more relevant for CO2 hyperreactivity than the modulation of the noradrenergic one", "Previous studies indicate that serotonin reuptake inhibitors do not appear to have serious cardiac side effects . However , the effects of these agents on respiratory measures have not been studied in detail . Several studies indicate that patients with anxiety exhibit irregular breathing patterns as measured by tidal volume and respiratory rate . In this study , we evaluated the effects of a serotonin reuptake inhibitor , paroxetine , on respiratory variability in patients with panic disorder ( n = 13 ) , using linear and nonlinear measures of regularity , approximate entropy ( APEN ) and a measure of chaos , the largest Lyapunov exponent ( LLE ) , with pre- and posttreatment lung volume time series ( 256 s long sample d at 4 Hz ) . Our results show that paroxetine significantly decreases some of the linear measures of variability and supine APEN and st and ing LLE of lung volume series after successful treatment . The implication s of these findings on respiratory and cardiovascular function have been discussed", "The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI . Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness . No extrapyramidal symptoms were reported . Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD , but study limitations must be considered and placebo-controlled studies are needed", "BACKGROUND Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors ( SSRIs ) have proved to be effective in the treatment of panic disorder . The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone . METHOD 161 patients with panic disorder with or without agoraphobia ( DSM-IV criteria ) underwent a manual-guided cognitive-behavioral therapy of 15 sessions . Forty-three unsuccessfully treated patients from this group were included in a double-blind , placebo-controlled , next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo . RESULTS Overall , patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior ( p anxiety discomfort ( p cognitive-behavioral therapy plus placebo condition did not . Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition , from 0.4 to 1.0 . CONCLUSION Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality . The importance of timely evaluation of treatment results is emphasized", "OBJECTIVE The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo . METHOD Forty-six out patients suffering from moderate to severe panic disorder with or without agoraphobia ( DSM-III-R criteria ) were r and omly assigned to a 10-week treatment protocol of regular aerobic exercise ( running ) , clomipramine ( 112.5 mg/day ) , or placebo pills . RESULTS The dropout rate was 31 % for the exercise group , 27 % for the placebo group , and 0 % for the clomipramine group . In comparison with placebo , both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures ( analysis of variance , last-observation-carried-forward method and completer analysis ) . A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively . Depressive symptoms were also significantly improved by exercise and clomipramine treatment . CONCLUSIONS These results suggest that regular aerobic exercise alone , in comparison with placebo , is associated with significant clinical improvement in patients suffering from panic disorder , but that it is less effective than treatment with clomipramine", "BACKGROUND More data are needed to guide next-step interventions for panic disorder refractory to initial intervention . METHOD This 24-week r and omized clinical trial ( RCT ) enrolled 46 patients with DSM-IV-defined panic disorder from November 2000 to April 2005 and consisted of 3 phases . Patients who failed to meet remission criteria were eligible for r and omization in the next treatment phase . Phase 1 was a 6-week lead-in with open-label sertraline flexibly dosed to 100 mg ( or escitalopram equivalent ) to prospect ively define treatment refractoriness ( lack of remission ) . Phase 2 was a 6-week double-blind RCT of ( 1 ) increased-dose selective serotonin reuptake inhibitor ( SSRI ) versus ( 2 ) continued SSRI plus placebo . Phase 3 was a 12-week RCT of added cognitive-behavioral therapy ( CBT ) compared to \" medication optimization \" with SSRI plus clonazepam . Primary endpoints were remission and change in Panic Disorder Severity Scale ( PDSS ) score in the intent-to-treat sample in each phase . RESULTS In phase 1 , 20.5 % ( 8/39 ) of the patients achieved remission , and only baseline severity predicted endpoint PDSS score ( beta [ SE ] = 1.04 [ 0.15 ] , t = 6.76 , P improvement or remission rates ( placebo 15 % [ n = 2 ] vs increased dose 9 % [ n = 1 ] : Fisher exact test P = NS ) . In phase 3 , remission was minimal ( medication optimization = 11 % [ n = 1 ] ; CBT = 10 % [ n = 1 ] ) , with a lack of group difference in PDSS score reduction ( t(17 ) = 0.51 , P > .60 ) consistent with a small effect size ( d = 0.24 ) . CONCLUSIONS Although power was limited and larger studies are needed , we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose . Further , augmentation with CBT or medication optimization with clonazepam augmentation in nonremitted panic after 12 weeks of an SSRI did not differ , suggesting that both are reasonable next-step options . However , low overall remission rates in this comorbid refractory population suggest that better predictors of response to specific treatments over time and additional interventions are needed . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00118417", "The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder ( PD ) . Twenty-five out patients having PD with or without agoraphobia were included . These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day . Treatment-resistant PD was defined as a less than 20 % reduction in score on the Panic Self- Question naire ( number of attacks per week ) ( PSQ ) and the Clinical Anxiety Scale With Panic Attacks ( CAS+PA ) . These patients continued to receive fluoxetine 20 mg/day and were r and omly assigned to additionally receive either pindolol ( 2.5 mg three times daily ) or placebo for the following 4 weeks . Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety , the Hamilton Rating Scale for Depression ( HAM-D ) , the CAS+PA , the NIMH Anxiety Scale , the PSQ , and the Clinical Global Impression Scale . The data were analyzed using a repeated- measures analysis of variance ( ANOVA ) and a t-test for independent sample s. Patients treated with the combination of pindolol and fluoxetine ( N = 13 ) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales , with the exception of HAM-D. The statistical differences were shown using the repeated- measures ANOVA ( baseline , week 2 , week 4 ) and also with t-tests from the second week of the trial . These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD", "Carbon dioxide ( CO2 ) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder ( PD ) . Anti-panic drugs decrease CO2 reactivity after the first days of treatment ; however , the clinical meaning of this finding has not yet been established . This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors ( SSRIs ) on CO2 reactivity and compared the relationships between 35 % CO2 hyperreactivity modulation and short-term clinical outcome . One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were r and omly assigned to treatment groups with imipramine , clomipramine , paroxetine , sertraline , or fluvoxamine . A double-blind , r and omized design was applied . Each patient received the 35 % CO2 challenge on days 0 , 7 , and 30 . The severity of clinical symptomatology was measured on days 0 and 30 . Decreased hyperreactivity to 35 % CO2 in all five treatment groups was already evident after the first week . The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement . Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month . The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity . They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “ respiratory ” PD", "BACKGROUND Cognitive behavioral therapy ( CBT ) and pharmacotherapy are efficacious for the short-term treatment of panic disorder . Less is known about the efficacy of these therapies for individuals who do not respond fully to short-term CBT . METHOD The current trial is a second-step stratified r and omized design comparing two treatment conditions-selective serotonin reuptake inhibitor ( SSRI ; paroxetine or citalopram ; n = 34 ) and continued CBT ( n = 24)-in a sample of individuals classified as treatment nonresponders to an initial course of CBT for panic disorder . Participants were r and omized to 3 months of treatment and then followed for an additional 9 months . Only treatment responders after 3 months were maintained on the treatment until 12-month follow-up . Data analysis focused on panic disorder symptoms and achievement of response status across the first 3 months of treatment . Final follow-up data are presented descriptively . RESULTS Participants in the SSRI condition showed significantly lower panic disorder symptoms as compared to continued CBT at 3 months . Results were similar when excluding individuals with comorbid major depression or analyzing the entire intent-to-treat sample . Group differences disappeared during 9-month naturalistic follow-up , although there was significant attrition and use of non study therapies in both arms . CONCLUSIONS These data suggest greater improvement in panic disorder symptoms when switching to SSRI after failure to fully respond to an initial course of CBT . Future studies should further investigate relapse following treatment discontinuation for nonresponders who became responders . Clinical trials.gov Identifier : NCT00000368 ; https:// clinical trials.gov/show/NCT00000368", "Background : Nonresponsiveness to therapy is generally acknowledged , but only a few studies have tested switching to psychotherapy . This study is one of the first to examine the malleability of treatment-resistant patients using acceptance and commitment therapy ( ACT ) . Methods : This was a r and omized controlled trial that included 43 patients diagnosed with primary panic disorder and /or agoraphobia ( PD/A ) with prior unsuccessful state-of-the-art treatment ( mean number of previous sessions = 42.2 ) . Patients were treated with an ACT manual administered by novice therapists and followed up for 6 months . They were r and omized to immediate treatment ( n = 33 ) or a 4-week waiting list ( n = 10 ) with delayed treatment ( n = 8) . Treatment consisted of eight sessions , implemented twice weekly over 4 weeks . Primary outcomes were measured with the Panic and Agoraphobia Scale ( PAS ) , the Clinical Global Impression ( CGI ) , and the Mobility Inventory ( MI ) . Results : At post-treatment , patients who received ACT reported significantly more improvements on the PAS and CGI ( d = 0.72 and 0.89 , respectively ) than those who were on the waiting list , while improvement on the MI ( d = 0.50 ) was nearly significant . Secondary outcomes were consistent with ACT theory . Follow-up assessment s indicated a stable and continued improvement after treatment . The dropout rate was low ( 9 % ) . Conclusions : Despite a clinical ly challenging sample and brief treatment administered by novice therapists , patients who received ACT reported significantly greater changes in functioning and symptomatology than those on the waiting list , with medium-to-large effect sizes that were maintained for at least 6 months . These proof-of-principle data suggest that ACT is a viable treatment option for treatment-resistant PD/A patients . Further work on switching to psychotherapy for nonresponders is clearly needed", "BACKGROUND Panic attacks can be induced in persons with panic disorder by inhalation of carbon dioxide . Hypercapnia also elicits a reflex hyperventilation , which is controlled in part by cholinergic mechanisms . This study investigated whether the exaggerated response to carbon dioxide in panic disorder ( PD ) can be modulated by antagonists of muscarinic cholinergic receptors . METHODS Twelve patients with PD received biperiden hydrochloride ( a muscarinic antagonist that crosses the blood-brain barrier ) , pirenzepine hydrochloride ( a muscarinic antagonist that does not cross the blood-brain barrier ) , or placebo 2 hours before a 35 % carbon dioxide-65 % oxygen respiratory challenge ( vs air as a placebo ) on 3 separate days , in a double-blind , r and om crossover design . RESULTS According to patients ' self-ratings of subjective anxiety , inhalation of the carbon dioxide/oxygen mixture provoked a significant and intense response after treatment with pirenzepine and placebo . After biperiden treatment , however , hypercapnia elicited a response profile similar to that elicited by air , whereby subjective anxiety remained similar to preinhalation levels . CONCLUSIONS Consistent with the hypothesis of the study , a central ly active muscarinic antagonist can block the response to carbon dioxide commonly observed in subjects with PD", "BACKGROUND Given growing evidence that respiratory dysregulation is a central feature of panic disorder ( PD ) interventions for panic that specifically target respiratory functions could prove clinical ly useful and scientifically informative . We tested the effectiveness of a new , brief , capnometry-assisted breathing therapy ( BRT ) on clinical and respiratory measures in PD . METHODS Thirty-seven participants with PD with or without agoraphobia were r and omly assigned to BRT or to a delayed-treatment control group . Clinical status , respiration rate , and end-tidal pCO(2 ) were assessed at baseline , post-treatment , 2-month and 12-month follow-up . Respiratory measures were also assessed during homework exercises using a portable capnometer as a feedback device . RESULTS Significant improvements ( in PD severity , agoraphobic avoidance , anxiety sensitivity , disability , and respiratory measures ) were seen in treated , but not untreated patients , with moderate to large effect sizes . Improvements were maintained at follow-up . Treatment compliance was high for session attendance and homework exercises ; dropouts were few . CONCLUSIONS The data provide preliminary evidence that raising end-tidal pCO(2 ) by means of capnometry feedback is therapeutically beneficial for panic patients . Replication and extension will be needed to verify this new treatment 's efficacy and determine its mechanisms", "INTRODUCTION Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent . More research examining pharmacotherapy augmentation strategies to improve outcomes is needed . METHODS In an 8-week , open-label , prospect i ve augmentation study , we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult out patients with generalized anxiety disorder ( n=13 ) or panic disorder ( n=10 ) who remained symptomatic despite treatment for at least 8 weeks with an adequate ( or maximally tolerated ) dose of typical pharmacotherapy . RESULTS Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores ( paired t=4.41 , df=22 , P sample of 23 individuals . Three subjects ( 13 % ) discontinued due to sedation , chest discomfort , and restlessness , respectively . CONCLUSION These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy", "Background : Improvements in quality of life ( QoL ) as well as symptomatic relief are important outcomes for the treatment of panic disorder ( PD ) . The aim of this study is to assess the impact of brief cognitive behavior group therapy ( CBGT ) for panic disorder on QoL and to identify the clinical features associated with these changes . Methods : Thirty-six patients with PD refractory to pharmacological treatment took part in a treatment protocol consisting of 12 sessions of CBGT . To evaluate the changes in QoL , the WHOQOL-bref was administered before and after treatment . Results : Thirty-two patients completed the treatment . Significant improvement in all domains of QoL was observed ( p general and anticipatory anxiety ( p = 0.018 ) and agoraphobic avoidance ( p = 0.046 ) . Consistent with previous findings , associations between QoL and panic-free status did not reach significance in this small study ( p = 0.094 ) . Conclusions : CBGT was efficacious in the treatment of PD ; the symptoms of anticipatory anxiety and avoidance appear to be more important than episodic panic episodes in affecting", "BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs", "Panic disorder is a common and disabling psychiatric disorder . Despite treatment advances , refractory panic disorder requires novel interventions . One such pharmacologic intervention with theoretical and case study support includes olanzapine , a thienobenzodiazepine medication currently approved for schizophrenia in the United States . Ten people with refractory DSM-IV diagnosed panic disorder completed an 8-week , open-label , flexible-dose clinical trial . Baseline , in-treatment , and end-of-treatment data for panic attacks , anticipatory anxiety , phobic avoidance , and impairment were collected . Data were analyzed using SPSS software . Refractory panic disorder patients required a wide dose range averaging 12.3 mg/day of olanzapine to significantly improve or ablate panic attacks . On the average , number of attacks decreased from 6.1/week at baseline to 1.1/week at the end of treatment , and anticipatory anxiety from 32 % of the day to 8 % of the day . At treatment end , 5 of 10 participants ( 50 % ) were panic free , 4 ( 40 % ) had one attack in the previous week , 1 ( 10 % ) had seven attacks in the previous week , and 6 of 10 participants ( 60 % ) were anticipatory anxiety free . There were also statistically and clinical ly significant improvements in impairment over the course of the trial . There were no significant changes in vital signs , emergent side effects , or average weight , although 6 of 10 people did gain weight . Olanzapine is potentially effective and safe in panic disorder . Due to study limitations , further clinical trials are needed to demonstrate effectiveness" ]

[ "OBJECTIVES Changes in body composition and blood chemistries between overweight adult subjects receiving a supplement containing either 3 g of konjac glucomannan/300 mg calcium carbonate or a placebo containing only 300 mg of calcium carbonate were compared as the primary objective . A secondary objective was to compare outcome differences between compliant and partially compliant subjects . METHODS A total of 83 overweight adults ( 66 women and 17 men ) completed a r and omized , double-blind , placebo-controlled protocol in which they received either a glucomannan or placebo supplement for 60 days . Dual-energy x-ray absorptiometry ( DEXA ) total body scans and a 42-measurement blood test were completed at baseline and 60 days later . Compliance was assessed by rating self-reports of ( 1 ) how many tablets were taken , ( 2 ) adherence to taking the tablets 30 minutes before eating , and ( 3 ) a sum of the ratings for ( 1 ) and ( 2 ) . An anonymous post study question naire and telephone calls were also completed by 80 ( 96 % ) of the participants who were used as the study cohort . RESULTS No statistically significant differences were found between the groups on changes from baseline on the DEXA and blood tests . However , when subjects were classified as either compliant or partially compliant using the compliance measures , statistically significant reductions in scale weight , percentage body fat , fat mass , total cholesterol , and low-density lipoprotein ( LDL ) cholesterol were found in the glucomannan group compared to the placebo group . CONCLUSIONS This study supports the efficacy glucomannan supplementation to reduce body weight , body fat , and circulating cholesterol levels without the concomitant loss of lean mass and bone density often associated with weight loss . However , these positive outcomes were not observable until corrections for compliance were applied", "The effects of the soluble fiber konjac glucomannan ( GM ) on serum cholesterol concentrations were investigated in 63 healthy men in a double-blind crossover , placebo-controlled study . After a 2-wk baseline period , the subjects were given 3.9 g GM or placebo daily for 4 wk . After a washout period of 2 wk , crossover took place , followed by another 4 wk of treatment . The subjects were encouraged not to change their ordinary diets or general lifestyle during the investigation . GM fibers reduced total cholesterol ( TC ) concentrations by 10 % ( P low-density-lipoprotein cholesterol ( LDL-C ) concentrations by 7.2 % ( P triglycerides by 23 % ( P systolic blood pressure by 2.5 % ( P High-density-lipoprotein cholesterol ( HDL-C ) and the ratio of LDL-C to HDL-C did not change significantly . No change in diastolic blood pressure or body weight was observed . No adverse effects were observed . The results of this study show that GM is an effective cholesterol-lowering dietary adjunct", "Background . Few safe and effective dietary supplements are available to promote weight loss . We evaluated the safety and efficacy of glucomannan , a water-soluble fiber supplement , for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets . Methods . Participants were r and omly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL ( 8 ounces ) of water one hour before breakfast , lunch , and dinner for 8 weeks . The primary efficacy outcome was change in body weight after 8 weeks . Other efficacy outcomes were changes in body composition , hunger/fullness , and lipid and glucose concentrations . Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels . Results . A total of 53 participants ( 18–65 years of age ; BMI 25–35 kg/m2 ) were enrolled and r and omized . The two groups did not differ with respect to baseline characteristics and compliance with the study supplement . At 8 weeks , there was no significant difference between the glucomannan and placebo groups in amount of weight loss ( −.40 ± .06 and −.43 ± .07 , resp . ) or other efficacy outcomes or in any of the safety outcomes . Conclusions . Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition , hunger/fullness , or lipid and glucose parameters . This trial is registered with NCT00613600", "The well-documented lipid-lowering effects of fibre may be related to its viscosity , a phenomenon that has been understudied , especially when fibre is given against the background of a typical North American ( NA ) diet . In this three-arm experiment , we compared the lipid-lowering effect of low-viscosity wheat bran ( WB ) , medium-viscosity psyllium ( PSY ) and a high-viscosity viscous fibre blend ( VFB ) , as part of a fibre intervention aim ed at increasing fibre intake to recommended levels within the context of a NA diet in apparently healthy individuals . Using a r and omised cross-over design , twenty-three participants ( twelve males and eleven females ; age 35 ( SD 12 ) years ; LDL-cholesterol ( C ) 2.9 ( SEM 0.6 ) mmol/l ) consuming a typical NA diet received a st and ard , fibre-enriched cereal , where approximately one-third of the fibre was either a low-viscosity ( 570 centipoise ( cP ) ) WB , medium-viscosity ( 14,300 cP ) PSY or a high-viscosity ( 136,300 cP ) novel VFB , for 3 weeks separated by washout periods of ≥ 2 weeks . There were no differences among the treatments in the amount of food consumed , total dietary fibre intake , reported physical activity and body weight . Final intake of the WB , PSY and VFB was 10.8 , 9.0 and 5.1 g , respectively . Reduction in LDL-C was greater with the VFB compared with the medium-viscosity PSY ( -12.6 ( SEM 3.5 ) % , P = 0.002 ) and low-viscosity WB ( -14.6 ( SEM 4.2 ) % , P = 0.003 ) . The magnitude of LDL-C reduction showed a positive association with fibre apparent viscosity ( r - 0.41 , P = 0.001 ) . Despite the smaller quantity consumed , the high-viscosity fibre lowered LDL-C to a greater extent than lower-viscosity fibres . These data support the inclusion of high-viscosity fibre in the diet to reduce plasma lipids among apparently healthy individuals consuming a typical NA diet", "Dietary fibres are frequently used for the treatment of paediatric obesity . The aim of this clinical trial is to evaluate the efficacy of glucomannan in the child obesity management . This experimental design was double blinded with a block r and omisation , alpha = 0.05 , beta = 0.2 and delta = 50 % . The study involved 60 children under 15 years of age ( mean age 11.2 years , mean overweight 46 % ) , 30 of them under glucomannan treatment ( 1 g twice a day for two months ) and 30 under placebo and the same schedule . The drug and the placebo were indistinguishable both for the family and the physician . During the two months study period the children followed a normocaloric diet evaluated every two weeks by a dietetic record book . At the beginning of the study the drug and the placebo groups were comparable in regards to anthropometric data . At the end , the mean overweight of the drug group was decreased from 49.5 % to 41 % and that of the placebo group from 43.9 % to 41.7 % . Both decreases were significant ( p no significant difference was observed between the drug and the placebo groups . The only significant difference concerned the lipid metabolism . The children under glucomannan treatment manifested a significant decrease of alpha-lipoprotein and an increase of pre-beta-lipoprotein and triglycerides ; the children under placebo manifested only a decrease of triglycerides and apo beta-lipoprotein . We suggest that this metabolic alteration may derive from a primary decrease of alpha-lipoprotein , most likely because of an inadequate water intake . ( ABSTRACT TRUNCATED AT 250 WORDS", "Carbohydrate-restricted diets ( CRDs ) promote weight loss , reductions in plasma triacylglycerol ( TAG ) levels , and increases in high-density lipoprotein cholesterol ( HDL-C ) levels but may cause undesirable low-density lipoprotein cholesterol ( LDL-C ) responses in some people . The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease . Using a parallel-arm , double-blind , placebo-controlled design , 30 overweight and obese men ( body mass index , 25 - 35 kg/m(2 ) ) were r and omly assigned to supplement a CRD with soluble fiber ( Konjac-mannan , 3g/d ) ( n = 15 ) or placebo ( n = 15 ) . Plasma lipids , anthropometrics , body composition , blood pressure , and nutrient intake were evaluated at baseline and at 6 and 12 weeks . Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria . Both groups experienced decreases in ( P body weight , percent body fat , systolic blood pressure , waist circumference , and plasma glucose levels . After 12 weeks , HDL-C and TAG improved significantly in the fiber ( 10 % and -34 % ) and placebo ( 14 % , -43 % ) groups . LDL-C decreased by 17.6 % ( P LDL-C reductions were significant in the placebo group only after 12 weeks ( -6.0 % , P LDL-C , adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone . Furthermore , a CRD led to clinical ly important positive alterations in cardiovascular disease risk factors", "AIM This paper evaluates the effect of the adjunct of the hydrosoluble fiber glucomannan to a Step-One-Diet in 40 plasma hypercholesterolemic children , during a r and omized controlled trial , to reduce plasma cholesterol . METHODS All the subjects recruited underwent an 8-week run in diet period ; a Step-One-Diet was prescribed . After that , they were r and omly allocated to one of two groups : Step-One-Diet only ( control ) , and Step-One-Diet plus glucomannan in gelatine capsules . After another 8 weeks of treatment , the results were compared within and between the two groups . RESULTS Glucomannan treated group showed decreased values in plasma total cholesterol ( TC ) and low density lipoprotein cholesterol ( LDL-C ) vs. control group after 8 weeks of treatment . The percentage decrease showed a statistically significant difference between sex groups . Decreases were observed in favor of female vs. male children in TC ( 24 % vs. 9 % ) and LDL-C ( 30 % vs. 9 % ) . CONCLUSIONS These results suggest that glucomannan may represent a rationale adjunct to diet therapy in primary prevention in high risk hypercholesterolemic children", "OBJECTIVE Primary dyslipidemias are major risk factors for cardiovascular disease and should be addressed early in life . The aim of this study was to evaluate , in children affected by primary hypercholesterolemia , the efficacy and tolerability of a short-term treatment with a dietary supplement containing glucomannan . METHODS A double-blind , r and omized , placebo-controlled , cross-over trial was conducted in 36 children ( aged 6 - 15 years ) affected by primary hypercholesterolemia . After a 4-week run-in period with dietary counseling , children received glucomannan or placebo twice-daily for 8 weeks , separated by a 4-week washout period . Lipid profile was assessed at baseline and after each treatment period . RESULTS Glucomannan significantly reduced total cholesterol ( TC ) by 5.1 % ( p = 0.008 ) , low-density lipoprotein cholesterol ( LDL-C ) levels by 7.3 % ( p = 0.008 ) and non-high-density lipoprotein cholesterol by 7.2 % ( p = 0.002 ) as compared with placebo . No significant differences were observed in high-density lipoprotein cholesterol , triglyceride , Apolipoprotein B , and Apolipoprotein A-I concentrations . According to sex , glucomannan significantly reduced in females , but not in males , TC ( -6.1 % , p = 0.011 ) and LDL cholesterol ( -9 % , p = 0.015 ) . No major adverse effects were recorded and only few patients experienced transitory intestinal discomfort . CONCLUSION Treatment with glucomannan of children affected by primary dyslipidemia is well-tolerated and effectively lowers total and LDL cholesterol in females and non-high-density lipoprotein cholesterol , but not Apolipoprotein B in both males and females", "Objective : The purpose of this study was to determine whether supplements of plant sterols and /or glucomannan improve lipid profile and cholesterol bio synthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments . Design : A r and omized , crossover study consisting of four phases of 21 days , with each phase separated by a 28-day washout . Setting : The Mary Emily Clinical Nutrition Research Unit of McGill University . Subjects : Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38–74 years . Interventions : Subjects were supplemented with plant sterols ( 1.8 g/day ) , glucomannan ( 10 g/day ) , a combination of glucomannan and plant sterols , and a placebo , provided in the form of bars . Results : Overall plasma cholesterol concentrations were lowered ( P ) . Plasma low-density lipoprotein ( LDL ) cholesterol concentrations were decreased ( P of lipid profiles did not differ between subject groups . Overall plasma lathosterol concentrations , an index of cholesterol bio synthesis , were lowered ( P improves plasma LDL cholesterol concentrations . Sponsorship : Forbes Medi-Tech Inc. , Vancouver , British Columbia , Canada", "Objectives : The present study was design ed to evaluate effects of konjac glucomannan ( KGM ) supplement ( 3.6 g/day ) for 28 days on blood lipid and glucose levels in hyperlipidemic type 2 diabetic patients and the possible mechanism for the reductions in blood lipid levels . Methods : Twenty-two diabetic subjects ( age 64.2 + 8.4 years , BMI 25.5 + 3.2 kg/m2 ) with elevated blood cholesterol levels ( fasting glucose between 6.7–14.4 mmol/L ) , but currently not taking lipid-lowering medication , were recruited to participate in a two 28-day period , r and omized , double-blind , crossover clinical trial . Fasting blood sample s drawn on the initial and final days of each period were determined for plasma lipids and glucose levels . Feces collected at the end of each experimental period were analyzed for neutral sterol and bile acid contents . Results : Compared with placebo , KGM effectively reduced plasma cholesterol ( 11.1 % , p = 0.0001 , adjusted α = 0.006 ) , LDL-cholesterol ( 20.7 % , p = 0.0004 , adjusted α = 0.006 ) , total/HDL cholesterol ratio ( 15.6 % , p = 0.0005 , adjusted α = 0.007 ) , ApoB ( 12.9 % , p = 0.0001 , adjusted α = 0.006 ) and fasting glucose ( 23.2 % , p = 0.002 , adjusted α = 0.008 ) . Plasma triglyceride , HDL-cholesterol , LDL/HDL cholesterol , postpr and ial glucose and body weight were not significant after adjustment by the Bonferroni-Hochberg procedure . Fecal neutral sterol and bile acid concentrations were increased by 18.0 % ( p = 0.004 ) and 75.4 % ( p with KGM supplement . Conclusions : The KGM supplement improved blood lipid levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in diabetic subjects . KGM could be an adjunct for the treatment of hyperlipidemic diabetic subjects", "An eight-week double-blind trial was conducted to test purified glucomannan fiber as a food supplement in 20 obese subjects . Glucomannan fiber ( from konjac root ) or placebo was given in 1-g doses ( two 500 mg capsules ) with 8 oz water , 1 h prior to each of three meals per d. Subjects were instructed not to change their eating or exercise patterns . Results showed a significant mean weight loss ( 5.5 lbs ) using glucomannan over an eight-week period . Serum cholesterol and low-density lipoprotein cholesterol were significantly reduced ( 21.7 and 15.0 mg/dl respectively ) in the glucomannan treated group . No adverse reactions to glucomannan were reported", " Two groups of 25 severely obese patients underwent 3 months of hypocaloric diet therapy either alone or associated with a glucomannan-based fibrous diet supplement ( approx . 4 g/die in 3 doses ) . The comparative analysis of the results obtained in both groups showed that the diet + glucomannan group had a more significant weight loss in relation to the fatty mass alone , an overall improvement in lipid status and carbohydrate tolerance , and a greater adherence to the diet in the absence of any relevant side effects . Due to the marked ability to satiate patients and the positive metabolic effects , glucomannan diet supplements have been found to be particularly efficacious and well tolerated even in the long-term treatment of severe obesity", "OBJECTIVE A low-fat , fiber-rich diet is the first step in the management for hypercholesterolemic children . Glucomannan ( GM ) is a natural fiber that has been demonstrated to lower total and LDL-cholesterol . The use of high-dose chromium-polynicotinate ( CP ) and policosanol ( PC ) has also shown cholesterol-lowering benefits . We aim ed at investigating the effects of low-dose CP or PC and their GM combination in hypercholesterolemic children . METHODS A double-blind trial was conducted in 120 children ( 60 M , 60 F , 9 ± 4 years , median 9.6 years , range : 3 - 16 years ) r and omly assigned to 5 neutraceutical and 1 placebo ( only resistant starch ) 8-week treatment groups . Fasting blood glucose ( FBG ) , total cholesterol ( CholT ) , triglycerides ( TG ) , HDL and LDL cholesterol were considered . RESULTS GM combination of low-dose CP or PC reduced CholT and LDL without changing HDL , TG and FBG . The highest post-treatment changes were seen after GM combination with CP ( CholT 85 ± 3 % and LDL 85 ± 5 % , of pretreatment ) which was significantly ( p with low-dose CP or PC and starch . When GM was associated with starch , there was no lipid lowering effect , which was an unexpected finding as compared to previous data with GM and no starch . No adverse effects were reported . CONCLUSION This is the first report to show the cholesterol-lowering efficacy of GM combined treatment with low-dose CP or PC . Further studies are needed to investigate the best combinations and doses of nutraceutics to be added to the st and ard GM treatment . The potential negative association of GM and nutraceutics with starch is clearly shown" ]

[ "A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983 . Menstrual characteristics , reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls . High gravidity , hysterectomy , female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer . Infertility and late age at menopause were associated with an increase in risk . While these factors were related , they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors", "BACKGROUND Ovarian germ cell tumors ( OGCT ) are highly curable when treated with cytoreductive surgery and platinum-based chemotherapy . We evaluated the safety and activity of a 3-day modified bleomycin , etoposide , and cisplatinum ( mBEP ) regimen in patients with OGCT . PATIENTS AND METHODS Patients with FIGO stages I-IV OGCT were treated with three ( stages I-III complete resection ) or four cycles ( incomplete resection or stage IV ) of bleomycin 15 mg iv , etoposide 120 mg/m(2 ) iv , and cisplatin 40 mg/m(2 ) iv for 3 days every 3 weeks . RESULTS Forty-eight patients ( 14 with dysgerminoma and 34 with non-dysgerminomatous tumors ) were included in our study . Most patients had stage I disease ( 65 % ) and complete resection of their tumor ( 67 % ) . Twenty percent of patients developed grade 3 or 4 neutropenia with 4 episodes of neutropenic fever . During follow-up ( median : 5 years ) , two patients developed progressive disease including one patient who died . All patients with stage I or II disease and all patients with dysgerminoma remain free of disease . However , 20 % of patients with non-dysgerminomatous tumors stage III or IV experienced progressive disease . CONCLUSION The modified 3-day BEP regimen was safe and effective in patients with OGCT . Further improvements are needed for patients with advanced , suboptimally debulked non-dysgerminomatous tumors ", "OBJECTIVES The objectives were to describe the clinical characteristics and prognosis of surgically treated patients with stage II and III serous borderline tumors of the ovary with noninvasive implants . MATERIAL S AND METHODS From 1990 to 2000 , 16 patients with stage II and III ovarian serous borderline tumors and noninvasive implants were diagnosed and prospect ively followed at our center . All patients underwent surgical treatment including staging and their pathology was review ed . Fifteen patients had thorough surgical staging by laparotomy , while one patient was staged laparoscopically . No patient was treated with adjuvant therapy ( radiation or chemotherapy ) after surgical treatment and none were lost to follow-up . RESULTS The mean age at diagnosis was 42 years ( range 26 - 59 ) . Fourteen patients were treated by abdominal hysterectomy , bilateral salpingo-oophorectomy , omentectomy , and multiple peritoneal biopsies , while 2 patients were treated conservatively for fertility preservation . Two patients underwent pelvic and para-aortic lymph node dissection . Fifteen of 16 patients had ovarian surface involvement with tumor . All patients but 2 had clinical evidence of extraovarian disease at the time of surgery . The mean duration of follow-up was 60.7 months ( range 2 - 134 months ) . Thirteen patients ( 81 % ) are alive without evidence of disease . Four patients ( 25 % ) required subsequent surgery for recurrent disease and all are still alive . Two patients have been treated with chemotherapy ( paclitaxel/carboplatin ) for progressive borderline disease , while an additional patient was treated after first relapse with chemotherapy for an invasive recurrence . CONCLUSIONS Carefully staged patients with advanced serous borderline tumors of the ovary and noninvasive implants have a good prognosis without adjuvant therapy", "PURPOSE This r and omized , multicenter , phase III noninferiority trial was design ed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin ( PLD ) with carboplatin ( CD ) compared with st and ard carboplatin and paclitaxel ( CP ) in patients with platinum-sensitive relapsed/recurrent ovarian cancer ( ROC ) . PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were r and omly assigned by stratified blocks to CD ( carboplatin area under the curve [ AUC ] 5 plus PLD 30 mg/m(2 ) ) every 4 weeks or CP ( carboplatin AUC 5 plus paclitaxel 175 mg/m(2 ) ) every 3 weeks for at least 6 cycles . Primary end point was progression-free survival ( PFS ) ; secondary end points were toxicity , quality of life , and overall survival . RESULTS Overall 976 patients were recruited . With median follow-up of 22 months , PFS for the CD arm was statistically superior to the CP arm ( hazard ratio , 0.821 ; 95 % CI , 0.72 to 0.94 ; P = .005 ) ; median PFS was 11.3 versus 9.4 months , respectively . Although overall survival data are immature for final analysis , we report here a total of 334 deaths . Overall severe nonhematologic toxicity ( 36.8 % v 28.4 % ; P CP arm . More frequent grade 2 or greater alopecia ( 83.6 % v 7 % ) , hypersensitivity reactions ( 18.8 % v 5.6 % ) , and sensory neuropathy ( 26.9 % v 4.9 % ) were observed in the CP arm ; more h and -foot syndrome ( grade 2 to 3 , 12.0 % v 2.2 % ) , nausea ( 35.2 % v 24.2 % ) , and mucositis ( grade 2 - 3 , 13.9 % v 7 % ) in the CD arm . CONCLUSION To our knowledge , this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over st and ard CP", "OBJECTIVE To assess feasibility and safety of fertility-sparing laparoscopic staging in women affected by unexpected ovarian cancer desiring to preserve their fertility . DESIGN Prospect i ve study . SETTING University clinic . PATIENT(S ) Twenty-seven patients already operated on elsewhere for a presumably benign ovarian cyst . INTERVENTION(S ) Laparoscopic fertility-sparing staging operations . MAIN OUTCOME MEASURE(S ) Perioperative and survival data , reproductive outcome . RESULT ( S ) Histologic findings after first surgery : 12 low malignant potential neoplasms , 11 invasive epithelial ovarian carcinomas,1 sex-cord stromal , and 3 germ cell neoplasms . Fertility-sparing staging consisted of exploration of the peritoneal cavity , peritoneal washing cytology , multiple peritoneal biopsies , omolateral adnexectomy ( except in borderline tumors ) , omentectomy , omolateral or bilateral pelvic and aortic lymph node sampling ( except in borderline tumors , well differentiated , mucinous , and granulosa cell ( GC ) neoplasms ) , endometrial biopsy , appendectomy in mucinous type . Overall , seven patients ( 26 % ) were upstaged . Six patients received adjuvant platinum-based chemotherapy . Two term pregnancies occurred . After a median follow-up of 20 months all patients are alive ; one patient has FIGO stage Ic clear cell carcinoma , which recurred 8 months after surgery . CONCLUSION ( S ) Laparoscopic fertility-sparing staging in early ovarian malignancies is feasible and safe in selected and counseled patients and should be performed in experienced gynecological oncology centers trained in endoscopic procedures", "This study was undertaken to determine whether secondary surgical debulking is beneficial for patients with malignant ovarian germ cell tumors ( OGCT ) . Twenty patients with OGCT treated at our institution between 1975 and 1992 were retrospectively identified and analyzed . Survival was analyzed using the life-table methods of Kaplan and Meier and the statistical significance of various perioperative factors was tested by both the log-rank and the Wilcoxon tests . Histologic tumor type included 8 immature teratomas , 6 mixed tumors , 5 endodermal sinus tumors , and 1 dysgerminoma . After primary surgery , all patients received chemotherapy -- non-platinum-based in 12 patients , platinum-based in 5 , and both types in 3 patients . Treatment failure was classified as progression in 14 patients , persistence in 3 , and recurrence in 3 . Salvage surgery consisted of exploratory laparotomy and tumor debulking in 18 patients , inguinal lymphadenectomy in 1 , and thoracotomy and wedge resection in 1 . Sixteen patients subsequently received salvage chemotherapy . At the time of analysis , 11 patients were alive disease-free , 1 was alive with tumor , 6 had died of tumor progression , and 2 had died of treatment-related complications . Survival of patients with immature teratoma who underwent salvage surgery was significantly better than survival of those with other tumor cell types ( P = 0.006 ) . In conclusion , although the role of secondary debulking in chemorefractory OGCT remains undetermined , it may have some benefit for a select group of patients , particularly those with immature teratoma", "PURPOSE To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer . PATIENTS AND METHODS Patients were r and omly allocated to receive paclitaxel 175 mg/m(2 ) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2 ) or carboplatin ( area under the plasma concentration-time curve of 5 ) , both on day 1 . The schedule was repeated every 3 weeks for at least six cycles . Women allocated to paclitaxel-cisplatin were admitted to the hospital , whereas the carboplatin regimen was administered to out patients . RESULTS A total of 208 eligible patients were r and omized . Both regimens could be delivered in an optimal dose and without significant delay . Paclitaxel-carboplatin produced significantly less nausea and vomiting ( P : peripheral neurotoxicity ( P : = .04 ) but more granulocytopenia and thrombocytopenia ( P : overall response rate in 132 patients with measurable disease was 64 % ( 84 of 132 patients ) , and in patients with elevated CA 125 levels at start , it was 74 % ( 132 of 178 patients ) . With a median follow-up time of 37 months , the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months . The small number of patients entered onto the study caused wide confidence intervals ( CIs ) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin ( hazards ratio , 1.07 ; 95 % CI , 0.78 to 1.48 ) and did not allow conclusions about efficacy . CONCLUSION Paclitaxel-carboplatin is a feasible regimen for out patients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin", "PURPOSE Vascular endothelial growth factor ( VEGF ) plays an important role in the biology of ovarian cancer ( OC ) . Inhibitors of VEGF suppress tumor growth in OC models . Metronomic chemotherapy , defined as frequent administration of low doses of cytotoxic chemotherapy , suppresses tumor growth , possibly by inhibiting angiogenesis . A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC . PATIENTS AND METHODS Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible . Up to two different regimens for recurrent disease were allowed . Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d . The primary end point was progression-free survival at 6 months . Plasma levels of VEGF , E-selectin , and thrombospondin-1 were obtained serially . RESULTS Seventy patients were enrolled . The probability of being alive and progression free at 6 months was 56 % ( + /- 6 % SE ) . A partial response was achieved in 17 patients ( 24 % ) . Median time to progression and survival were 7.2 and 16.9 months , respectively . The most common serious toxicities were hypertension , fatigue , and pain . Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula , two episodes each of CNS ischemia and pulmonary hypertension , and one episode each of gastrointestinal bleeding and wound healing complication . There were three treatment-related deaths . Levels of VEGF , E-selectin , and thrombospondin-1 were not associated with clinical outcome . CONCLUSION The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC . Further study of this combination is warranted", "BACKGROUND During the childbearing years , the st and ard fertility-sparing treatment for bilateral borderline ovarian tumours ( BOTs ) is the unilateral oophorectomy plus controlateral cystectomy . The aim of the present study was to compare the effects of two laparoscopic fertility-sparing surgical procedures for the treatment of bilateral BOTs on recurrence and fertility in young women who desire to conceive as soon as possible . METHODS Thirty-two women affected by bilateral early-stage BOTs who desired to conceive were r and omized to receive bilateral cystectomy ( experimental group , n=15 ) or oophorectomy plus controlateral cystectomy ( control group , n=17 ) . At the first recurrence after childbearing completion , each patient was treated with non-conservative st and ard treatment . Recurrences and reproductive events were recorded . RESULTS After a follow-up period of 81 months ( 19 inter-quartile ; 60 - 96 range ) , the cumulative pregnancy rate ( CPR ) ( 14/15 versus 9/17 ; P=0.003 ) and the cumulative probability of first pregnancy ( P= 0.011 ) were significantly higher in the experimental than in control group . No significant ( P=0.358 ) difference between groups was detected in cumulative probability of first recurrence . CONCLUSIONS The laparoscopic bilateral cystectomy followed by non-conservative treatment performed at the first recurrence after the childbearing completion is an effective surgical strategy for patients with bilateral early-stage BOTs who desire to conceive as soon as possible", "Question What is the optimal chemotherapy treatment for women with recurrent ovarian cancer who have previously received platinum-based chemotherapy ? Perspectives Currently , st and ard primary therapy for advanced disease involves a combination of maximal cytoreductive surgery and chemotherapy with carboplatin plus paclitaxel or with carboplatin alone . Despite initial high response rates , a large proportion of patients relapse , result ing in a therapeutic challenge . Because these patients are not curable , the goal of therapy becomes improvement in both quality and length of life . The search has therefore been to find active agents for women with recurrent disease following platinum-based chemotherapy . Outcomes Outcomes of interest included any combination of tumour response rate , progression-free survival , overall survival , adverse events , and quality of life . Methodology The medline , embase , and Cochrane Library data bases were systematic ally search ed for primary articles and practice guidelines . The result ing evidence informed the development of clinical practice recommendations . The systematic review and recommendations were approved by the Report Approval Panel of the Program in Evidence -Based Care , and by the Gynecology Cancer Disease Site Group ( dsg ) . The practice guideline was externally review ed by a sample of practitioners from Ontario , Canada . Results Thirteen r and omized trials compared various chemotherapy regimens for patients with recurrent ovarian cancer . In five of the thirteen trials in which 100 % of patients were considered sensitive to platinum-containing chemotherapy , further platinum-based combination chemotherapy significantly improved response rates ( two trials ) , progression-free survival ( four trials ) , and overall survival ( three trials ) when compared with single-agent chemotherapy involving carboplatin or paclitaxel . Only two of these r and omized trials compared the same chemotherapy regimens : carboplatin alone versus the combination of carboplatin and paclitaxel . Both trials were consistent in reporting improved survival outcomes with the combination of carboplatin and paclitaxel . In one trial , the combination of carboplatin and gemcitabine result ed in significantly higher response rates and improved progression-free survival when compared with carboplatin alone . Median survival with carboplatin alone ranged from 17 months to 24 months in four trials . In eight of the thirteen trials in which 35%–100 % of patients had platinum-refractory or -resistant disease , one trial reported a statistically significant 2-month improvement in overall survival with liposomal doxorubicin as compared with topotecan ( 15 months vs. 13 months , p = 0.038 ; hazard ratio : 1.23 ; 95 % confidence interval : 1.01 to 1.50 ) . In that trial , because of the limited clinical benefit and the unusual finding that a survival difference emerged only after a year of treatment with no corresponding improvement in the rate of response or of progression-free survival , the authors concluded that further confirmation by results from r and omized trials were needed to establish the superiority of one agent over another in their trial . In one trial , topotecan was superior to treosulphan in patient progression-free survival by a span of approximately 2 months ( 5.4 months vs. 3.0 months , p Toxicity was reported in all of the r and omized trials , and although data on adverse events varied by treatment regimen , the observed adverse events correlated with known toxicity profiles . As expected , combination chemotherapy was associated with higher rates of adverse events . Practice Guideline Target Population This clinical recommendation applies to women with recurrent epithelial ovarian cancer who have previously received platinum-based chemotherapy . Of specific interest are women who have previously shown sensitivity to platinum therapy and those who previously were refractory or resistant to platinum-based chemotherapy . As a general categorization within what is actually a continuum , “ platinum sensitivity ” refers to disease recurrence 6 months or more after prior platinum-containing chemotherapy , and “ platinum resistance ” refers to a response to platinum-based chemotherapy followed by relapse less than 6 months after chemotherapy is stopped . “ Platinum-refractory disease ” refers to a lack of response or to progression while on platinum-based chemotherapy . Recommendations Although the body of evidence that informs the clinical recommendations is based on r and omized trial data , those data are incomplete . Based on the available data and expert consensus opinion , the Gynecology Cancer dsg makes these recommendations : Systemic therapy for recurrent ovarian cancer is not curative . It is therefore recognized that each patient must be individually assessed to determine optimal therapy in terms of recurrence , sensitivity to platinum , toxicity , ease of administration , and patient preference . All suitable patients should be offered the opportunity to participate in r and omized trials , if available . In the absence of contraindications , combination platinum-based chemotherapy should be considered for patients with prior sensitivity to platinum-containing chemotherapy . As compared with carboplatin alone , the combination of carboplatin and paclitaxel significantly improved both progression-free and overall survival . If combination platinum-based chemotherapy is not indicated , then a single platinum agent should be considered . Carboplatin has demonstrated efficacy across trials and has a manageable toxicity profile . If a single platinum agent is not being considered , then monotherapy with paclitaxel , topotecan , or pegylated liposomal doxorubicin are seen as reasonable treatment options . Some patients may be repeatedly sensitive to treatment and may benefit from multiple lines of chemotherapy . For patients with platinum-refractory or platinum-resistant disease , the goals of treatment should be to improve quality of life by extending the symptom-free interval , by reducing symptom intensity , and by increasing progression-free interval , and , if possible , to prolong life . With non-platinum agents , monotherapy should be considered because no advantage appears to accrue to the use of non-platinum-containing combination chemotherapy in this group of patients . Single-agent paclitaxel , topotecan , or pegylated liposomal doxorubicin have demonstrated activity in this patient population and are reasonable treatment options . No evidence either supports or refutes the use of more than one line of chemotherapy in patients with platinum-refractory or platinum-resistant recurrence . Many treatment options have shown modest response rates , but their benefits over best supportive care have not been studied in clinical trials", "This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to , or relapsed following , platinum-based chemotherapy . Forty-seven patients participated , 20 of whom had received more than one prior treatment . Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy . Initially , oral etoposide , 50 mg b.d . ( regardless of patient size ) , was given for 14 days on a 21-day cycle . However , after encountering toxicity , the schedule was modified to 7 days ' treatment escalating to 10 then 14 days if well tolerated . Among 41 assessable patients there were two complete and eight partial objective responses ( 24 % response rate ; 95 % confidence interval 12 - 41 % ) . Nine further patients ( 22 % ) had stable disease , four with a sustained fall of > 50 % in CA-125 . Median duration of response or stable disease was 35 weeks ( range 21 - 49 ) . Overall median survival was 41 weeks from study entry ( range 2 to 96 + weeks ) . Toxicity for most patients was mild , but sporadic severe myelotoxicity occurred , with two treatment-related deaths . Risk factors for severe toxicity were : performance status 3 ; hepatic impairment ; renal impairment . We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy . It has significant toxicity which may be avoided by appropriate patient selection and an escalating- duration schedule", "PURPOSE The aim of this study was to perform an evaluation of outcome and the role of surgical staging components in malignant germ cell tumors ( GCT ) of the ovary in children and adolescents . METHODS From 1990 to 1996 , 2 intergroup trials for malignant GCT were undertaken by Pediatric Oncology Group ( POG ) and Children 's Cancer Study Group ( CCG ) . Stage I-II patients were treated with surgical resection and 4 cycles of st and ard dose cisplatin ( 100 mg/m2/cycle ) , etoposide , and bleomycin ( PEB ) chemotherapy . Stage III-IV patients were treated with surgical resection and r and omly assigned to chemotherapy with PEB or high-dose cisplatin ( 200 mg/m2/cycle ) with etoposide and bleomycin ( HDPEB ) . Patients unresectable at diagnosis had second-look operation after 4 cycles of chemotherapy if residual tumor was seen on imaging studies . IRB approval of the protocol s was obtained at each participating institution . An analysis of outcome data , operative notes , and pathology reports in girls with ovarian primary site was done for this report . RESULTS There were 131 patients with ovarian primary tumors of 515 entered on these studies . Mean age was 11.9 years ( range , 1.4 to 20 years ) . Six-year survival rate was stage , I 95.1 % ; stage II , 93.8 % ; stage III , 98.3 % ; stage IV , 93.3 % . In only 3 of 131 patients were surgical guidelines followed completely . Surgical omissions result ing in protocol noncompliance result ed from failure to biopsy bilateral nodes ( 97 % ) , no omentectomy ( 36 % ) , no peritoneal cytology ( 21 % ) , no contralateral ovary biopsy ( 59 % ) . More aggressive procedure than recommended by guidelines included total hysterectomy and bilateral salpingo-oophorectomy in 6 patients and retroperitoneal node dissection in 10 patients . Correlation of gross operative findings with pathology results was carried out for ascites , lymph nodes , implants , omentum , and contralateral ovary . CONCLUSIONS Pediatric ovarian malignant GCT ( stages I-IV ) have excellent survival with conservative surgical resection and platinum-based chemotherapy . Survival appears to have been unaffected by deviations from surgical guidelines . New surgical guidelines are proposed based on correlation of gross findings , histology , and outcome in these intergroup trials", "PURPOSE In r and omized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer . Although in nonr and omized trials , carboplatin and paclitaxel was a less toxic and highly active combination regimen , there remained concern regarding its efficacy in patients with small-volume , resected , stage III disease . Thus , we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population . PATIENTS AND METHODS Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were r and omly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 ( arm I ) , or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours ( arm II ) . RESULTS Seven hundred ninety-two eligible patients were enrolled onto the study . Prognostic factors were similar in the two treatment groups . Gastrointestinal , renal , and metabolic toxicity , as well as grade 4 leukopenia , were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II . Neurologic toxicity was similar in both regimens . Median progression-free survival and overall survival were 19.4 and 48.7 months , respectively , for arm I compared with 20.7 and 57.4 months , respectively , for arm II . The relative risk ( RR ) of progression for the carboplatin plus paclitaxel group was 0.88 ( 95 % confidence interval [ CI ] , 0.75 to 1.03 ) and the RR of death was 0.84 ( 95 % CI , 0.70 to 1.02 ) . CONCLUSION In patients with advanced ovarian cancer , a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity , is easier to administer , and is not inferior , when compared with cisplatin plus paclitaxel", " Objective . Currently , no prospect i ve study supports or refutes the value of secondary cytoreductive surgery in patients with ovarian cancer . We therefore review ed the surgical data of patients who underwent second‐look laparotomy ( SLL ) with or without secondary cytoreductive surgery at our department", "BACKGROUND Borderline ovarian tumors often affect women of childbearing age and the prognosis is outst and ing . Given the young age of several patients and the good prognosis , fertility-sparing surgery is considered adequate for stage I tumors . However , women treated conservatively have a relatively small but well-defined risk of recurrence and no study has specifically addressed the optimal follow-up technique . METHODS From 1981 to 1997 , 164 women underwent fertility-sparing surgery for stage I borderline ovarian tumor and were followed prospect ively . After surgery all women underwent physical examination and ultrasound examination every 3 months for 2 years after first diagnosis and every 6 months thereafter . Measurement of serum CA 125 levels was planned every 6 months in patients with a serous tumor . RESULTS With a median follow-up of 71 , months 28 women treated with fertility-sparing surgery ( 28/164 = 17 % ) had either recurrence of borderline tumor ( 23 ) or recurrence with carcinoma . Complete details of follow-up procedures are available for 24 women and they represent the study population . An abnormal adnexal mass was detected in 18 of 19 women with recurrent borderline tumor . One patient had diagnosis due to persistent free fluid . All five women with invasive carcinoma had diagnosis of a complex adnexal mass . Gynecologic examination was suspicious ( palpable mass ) in 7 cases and obviously abnormal ( large mass or nodules ) in another 7 . CA 125 serum levels were elevated in 8 cases . CONCLUSION Transvaginal ultrasound is currently the most effective diagnostic technique for the follow-up of young patients treated conservatively for early borderline ovarian tumor", "BACKGROUND The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one . We carried out a multicenter , open r and omized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer . METHODS Between August 1991 and January 2000 , 477 patients in 84 centers in five countries were r and omly assigned to receive either adjuvant chemotherapy immediately following surgery ( n = 241 ) or no adjuvant chemotherapy until clinical ly indicated ( n = 236 ) . Kaplan-Meier curves of overall survival and recurrence-free survival were compared using the Mantel-Cox version of the log-rank test . All statistical tests were two-sided . RESULTS Women who received adjuvant chemotherapy had better overall survival than women who did not ( hazard ratio [ HR ] of 0.66 , 95 % confidence interval [ CI ] = 0.45 to 0.97 ; P = .03 ) . These results translate into 5-year survival figures of 70 % for women who did not receive adjuvant chemotherapy and 79 % for women who did receive adjuvant chemotherapy , a difference of 9 % ( 95 % CI = 1 % to 15 % ) . Adjuvant chemotherapy also improved recurrence-free survival ( HR = 0.65 ; 95 % CI = 0.46 to 0.91 ; P = .01 ) . These results translate into 5-year recurrence-free survival figures of 62 % for women who did not receive adjuvant chemotherapy and 73 % for women who did receive adjuvant chemotherapy , a difference of 11 % ( 95 % CI = 3 % to 18 % ) . CONCLUSION These results suggest that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer", "Many patients with advanced ovarian cancer will develop recurrent disease . For those patients who have recurrence of disease at least 6 months after initial therapy , the paclitaxel – platinum combination has been shown to be a superior treatment to platinum monotherapy . However , many patients develop clinical ly relevant neurotoxicity , frequently result ing in treatment discontinuation . The efficacy and safety of an alternative regimen that does not show significant neurotoxicity were evaluated by comparing gemcitabine – carboplatin with carboplatin in platinum-sensitive recurrent ovarian cancer patients in a Gynecologic Cancer InterGroup trial of the Arbeitsgemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group , the National Cancer Institute of Canada Clinical Trials Group , and the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group . Participants with recurrent platinum-sensitive ovarian cancer were r and omly assigned to receive either gemcitabine – carboplatin or carboplatin every 21 days . The primary objective was to compare progression-free survival ( PFS ) between the groups . From September 1999 to April 2002 , 356 patients ( 178 participants received gemcitabine – carboplatin , 178 received carboplatin only ) were r and omized to treatment . Patients received six cycles of either gemcitabine – carboplatin or carboplatin . With a median follow-up of 17 months , median PFS was 8.6 months for gemcitabine – carboplatin ( 95 % confidence interval [ CI ] 7.9–9.7 months ) and 5.8 months for carboplatin ( 95 % CI 5.2–7.1 months ; hazard ratio [ HR ] 0.72 [ 95 % CI 0.58–0.90 ; P = 0.0032 ] ) . The response rate for the gemcitabine – carboplatin group was 47.2 % ( 95 % CI 39.9–54.5 % ) and 30.9 % for carboplatin group ( 95 % CI 24.1–37.7 % ; P = 0.0016 ) . The HR for overall survival was 0.96 ( 95 % CI 0.75–1.23 ; P = 0.7349 ) . Patients treated with gemcitabine – carboplatin reported significantly faster palliation of abdominal symptoms and a significantly improved global quality of life . Gemcitabine – carboplatin treatment significantly improves the PFS of patients with platinum-sensitive recurrent ovarian cancer ", "BACKGROUND Paclitaxel and carboplatin given every 3 weeks is st and ard treatment for advanced ovarian carcinoma . Attempts to improve patient survival by including other drugs have yielded disappointing results . We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer . METHODS Patients with stage II to IV epithelial ovarian cancer , fallopian tube cancer , or primary peritoneal cancer were eligible for enrolment in this phase 3 , open-label , r and omised controlled trial at 85 centres in Japan . Patients were r and omly assigned by computer-generated r and omisation sequence to receive six cycles of either paclitaxel ( 180 mg/m(2 ) ; 3-h intravenous infusion ) plus carboplatin ( area under the curve [ AUC ] 6 mg/mL per min ) , given on day 1 of a 21-day cycle ( conventional regimen ; n=320 ) , or dose-dense paclitaxel ( 80 mg/m(2 ) ; 1-h intravenous infusion ) given on days 1 , 8 , and 15 plus carboplatin given on day 1 of a 21-day cycle ( dose-dense regimen ; n=317 ) . The primary endpoint was progression-free survival . Analysis was by intention to treat ( ITT ) . This trial is registered with Clinical Trials.gov , number NCT00226915 . FINDINGS 631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population ( dose-dense regimen , n=312 ; conventional regimen , n=319 ) . Median progression-free survival was longer in the dose-dense treatment group ( 28.0 months , 95 % CI 22.3 - 35.4 ) than in the conventional treatment group ( 17.2 months , 15.7 - 21.1 ; hazard ratio [ HR ] 0.71 ; 95 % CI 0.58 - 0.88 ; p=0.0015 ) . Overall survival at 3 years was higher in the dose-dense regimen group ( 72.1 % ) than in the conventional treatment group ( 65.1 % ; HR 0.75 , 0.57 - 0.98 ; p=0.03 ) . 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early . Reasons for participant dropout were balanced between the groups , apart from withdrawal because of toxicity , which was higher in the dose-dense regimen group than in the conventional regimen group ( n=113 vs n=69 ) . The most common adverse event was neutropenia ( dose-dense regimen , 286 [ 92 % ] of 312 ; conventional regimen , 276 [ 88 % ] of 314 ) . The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group ( 214 [ 69 % ] ) than in the conventional treatment group ( 137 [ 44 % ] ; p frequencies of other toxic effects were similar between groups . INTERPRETATION Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer . FUNDING Bristol-Myers Squibb", "OBJECTIVES To assess feasibility , complications and efficacy of secondary surgical cytoreduction ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) in a selected group of platinum-sensitive recurrent ovarian cancer patients . METHODS Recurrent ovarian cancer patients with a platinum-free interval of at least 6 months were prospect ively enrolled . After complete CRS they were su bmi tted to intraperitoneal perfusion of oxaplatinum ( 460 mg/m(2 ) ) heated to 41.5 degrees C for 30 min . Then they received systemic chemotherapy with taxotere 75 mg/m(2 ) and oxaliplatin 100 mg/m(2 ) for 6 cycles . Patients were followed up routinely until recurrence or death . RESULTS Twenty-five recurrent ovarian cancer patients were valuable for the study . The median Platinum Free Interval ( PFI ) was 25 months ( range 7 - 67 ) . The majority of the patients ( 76 % ) had diffuse carcinosis . Nobody had ascites . An optimal residual disease was obtained in all patients . The median duration of CRS+HIPEC was 312 min ( range 138 - 619 ) . Median intensive care unit ( ICU ) stay was 2 days ( 1 - 6 ) , median hospital stay was 13 days ( 7 - 30 ) . Post-operative major complications were observed in 7 patients ( 28 % ) . Post-operative mortality was 0 % . With a median follow-up time of 18 months ( range 3 - 38 ) , 24 patients ( 96 % ) are alive , but seven women ( 28 % ) have relapsed . CONCLUSIONS Adequate pre-operative selection can improve feasibility of CRS and HIPEC . Morbidity rate is comparable to aggressive cytoreduction without HIPEC . Although associated with some post-operative morbidity , long-term results are encouraging , waiting for larger series and longer follow-up data", "PURPOSE The management of recurrent ovarian cancer remains controversial . Single-agent topotecan is an established treatment option , and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine . PATIENTS AND METHODS Women with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were r and omly assigned to topotecan monotherapy 1.25 mg/m(2)/d , topotecan 1.0 mg/m(2 ) plus oral etoposide 50 mg/d , or topotecan 0.5 mg/m(2)/d plus gemcitabine 800 mg/m(2 ) on day 1 and 600 mg/m(2 ) on day 8 every 3 weeks . Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months , respectively . The primary end point was overall survival . Secondary end points included progression-free survival , objective response rates , toxicity , and quality of life ( as measured by the European Organisation for Research and Treatment of Cancer [ EORTC ] 30-item Quality -of-Life Question naire ) . RESULTS The trial enrolled 502 patients with a mean age of 60.5 years ( + /- 10.2 years ) , 208 of whom were platinum resistant . Median overall survival was 17.2 months ( 95 % CI , 13.5 to 21.9 months ) with topotecan , 17.8 months ( 95 % CI , 13.7 to 20.0 months ) with topotecan plus etoposide ( log-rank P = .7647 ) , and 15.2 months ( 95 % CI , 11.3 to 20.9 months ) with topotecan plus gemcitabine ( log-rank P = .2344 ) . Platinum-sensitive patients lived significantly longer than platinum-refractory patients ( 21.9 v 10.6 months ) . The median progression-free survival was 7.0 , 7.8 , and 6.3 months , respectively . Objective response rates were 27.8 % , 36.1 % , and 31.6 % , respectively . Patients under combined treatment were at higher risk of severe thrombocytopenia . CONCLUSION Nonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer", "PURPOSE This phase II study was design ed to determine the toxicity and activity of single-agent gemcitabine in heavily pretreated patients with germ cell tumors . PATIENTS AND METHODS From March 1996 through November 1997 , 21 patients were enrolled onto a phase II study of gemcitabine 1,200 mg/m2 , given on days 1 , 8 , and 15 every 4 weeks . One patient was unassessable because he never received any gemcitabine . Thirteen of 20 patients had received three prior regimens , and 13 patients were platinum refractory ( progression during or within 4 weeks of platinum treatment ) . There were five extragonadal cases and two patients with late relapse ( relapse beyond 2 years ) . RESULTS Gemcitabine was well tolerated . Only one patient had grade 3 or 4 nonhematologic toxicity ( grade 3 nausea ) . Six of 20 patients had grade 3 leukopenia . There were no episodes of granulocytopenic fever , and no patient required platelet transfusion . Three ( 15 % ) of 20 patients achieved an objective response , including one complete remission . Three additional patients had a minor radiographic or serologic response . CONCLUSION Gemcitabine had definite activity in this heavily pretreated germ cell tumor patient population", "Because of scarce data from larger series and nonhomogeneous selection criteria , further information is needed on peritonectomy with hyperthermic intraperitoneal chemotherapy ( HIPEC ) in managing patients with ovarian peritoneal carcinomatosis", "PURPOSE The objective of this study was to compare the quality of life ( QoL ) of ovarian cancer patients treated with paclitaxel/carboplatin ( TC ) versus paclitaxel/cisplatin ( PT ) and to determine the impact of treatment toxicity on the various QoL domains . PATIENTS AND METHODS In this phase III trial , 798 patients with ovarian cancer stages IIB-IV were r and omly assigned to receive TC or PT . The primary end point was progression-free survival ; secondary end points included toxicity , QoL , and response to treatment . Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 before treatment , within 3 days before the second and the fourth chemotherapy cycle , and 3 weeks after completion of chemotherapy . RESULTS Previously reported data showed that patients undergoing TC or PT did not differ in progression-free survival and overall survival . However , the TC arm was superior , indicating a better overall QoL compared with the PT arm . Controlling for toxicity and age , a significant treatment by assessment time interaction was found for four QoL functioning scales and three symptoms scales . Patients in the TC arm showed better means scores after treatment on overall QoL ( P = .012 ) , physical functioning ( P = .012 ) , role functioning ( P = .005 ) , and cognitive functioning ( P = .024 ) , compared with the PT arm . Concerning symptom experience , patients undergoing TC showed less nausea and vomiting ( P appetite loss ( P fatigue ( P = .033 ) after completion of treatment compared with patients undergoing PT . CONCLUSION The TC regimen achieved better QoL outcomes compared with the PT regimen . Thus , clinicians may consider replacing cisplatin with carboplatin when treating ovarian cancer patients with chemotherapy", "This study defines the psychometric properties of the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life ( QOL ) question naire design ed to measure the QOL of patients with ovarian cancer . The ovarian cancer module ( EORTC QLQ-OV28 ) was developed to supplement the EORTC QLQ-C30 . The core question naire and the QLQ-OV28 were prospect ively administered to 368 ovarian cancer patients after they had been treated with radical or debulking surgery followed by chemotherapy . The QLQ-OV28 module assesses abdominal/gastrointestinal symptoms , peripheral neuropathy , other chemotherapy side-effects , hormonal/menopausal symptoms , body image , attitude to disease/treatment and sexual functioning . Question naires were well accepted by patients , baseline compliance rates were 86 % , 72 % provided a second assessment , less than 3 % of the items had missing data . Multi-trait scaling analyses confirmed the hypothesised scales . All hypothesised scales exhibited good psychometric properties . These results support the clinical and psychometric validity of the EORTC QLQ-OV28 module as a supplement to the EORTC QLQ-C30", "Primary surgery followed by platinum‐taxane based chemotherapy has been the st and ard therapy in advanced ovarian cancer . However , the prognostic role of complete and so‐called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined", "PURPOSE To assess progression-free survival ( PFS ) and overall survival ( OS ) in patients with suboptimally debulked epithelial ovarian cancer receiving cisplatin ( 100 mg/m(2 ) ) or 24-hour infusion paclitaxel ( 200 mg/m(2 ) ) or the combination of paclitaxel ( 135 mg/m(2 ) ) followed by cisplatin ( 75 mg/m(2 ) ) . PATIENTS AND METHODS After stratification for disease measurability , patients were r and omized to receive six cycles of one of the treatments every 3 weeks . If measurable , complete response ( CR ) or partial response ( PR ) was determined . RESULTS Six hundred fourteen of 648 patients who entered onto the trial were eligible . Monotherapies were discontinued more frequently ( cisplatin because of toxicity or patient refusal [ 17 % ] , and paclitaxel because of progression [ 20 % ] ) compared with the combination therapy ( 7 % and 6 % , respectively ) . Neutropenia , fever , and alopecia were more severe with paclitaxel-containing regimens ; whereas anemia , thrombocytopenia , neurotoxicity , nephrotoxicity , and gastrointestinal toxicity were more severe with cisplatin-containing regimens . The CR/PR rates on paclitaxel monotherapy were significantly lower compared with the cisplatin regimens ( 42 % v 67 % , respectively ; P relative hazard ( RH ) of first progression or death was significantly greater among those r and omized to paclitaxel ( RH = 1.41 ; 95 % confidence interval [ CI ] , 1.15 to 1.73 ; P cisplatin ; however , RH did not differ significantly between the two cisplatin regimens ( RH = 1.06 ; 95 % CI , 0.895 to 1.30 ) . Relative to cisplatin , the death rate on paclitaxel was 15 % greater ( RH = 1.15 ; 95 % CI , 0 . 929 to 1.42 ) , and the death rate on the combination treatment was 1 % less ( RH = 0.99 ; 95 % CI , 0.795 to 1.23 ) . These differences among treatment groups were not statistically significant ( P = .31 ) . CONCLUSION Cisplatin alone or in combination yielded superior response rates and PFS relative to paclitaxel . However , OS was similar in all three arms , and the combination therapy had a better toxicity profile . Therefore , the combination of cisplatin and paclitaxel remains the preferred initial treatment option", "A case-control study of reproductive factors and cancer of the ovary was conducted during 1989 - 1992 in metropolitan Toronto and nearby areas of Southern Ontario , Canada . In total , 450 women aged 35 - 79 years with histologically verified new primary epithelial ovarian cancers were interviewed concerning their reproductive histories . Over the same time period , 564 r and omly selected population controls , frequency-matched to the cases according to three 15-year age groups , were also interviewed . Continuous unconditional logistic regression methods were used for analysis . It was found that childbearing and use of oral contraceptives were associated with significant decreasing trends in risk of ovarian cancer ; the respective odds ratios were 0.78 for each full-term pregnancy ( p Hysterectomy was also associated with reduced risk , even after more than 20 years . Among parous women , infertility did not appear to affect risk ; for Noneiparous women , some evidence of increased risk was present , although fertility problems were reported by only a small fraction of Noneiparae . It is suggested that the relatively lower parity of cases as compared with controls may be due to voluntary choices for having fewer children", "OBJECTIVE Provide long-term follow-up data for women treated in a r and omized multicenter study of pegylated liposomal doxorubicin compared with topotecan . METHODS Patients with epithelial ovarian cancer that recurred after or failed to respond to first-line platinum-based chemotherapy were r and omized to receive pegylated liposomal doxorubicin 50 mg/m(2 ) every 28 days ( n = 239 ) or topotecan 1.5 mg/m(2 ) per day for 5 days every 21 days ( n = 235 ) . Patients were stratified prospect ively based on response to initial platinum-based chemotherapy as well as the presence or absence of bulky disease . Most patients had been previously treated with platinum and taxanes ( 74 % in the pegylated liposomal doxorubicin group and 72 % in the topotecan group ) . Survival data are mature : 87 % of patients have died ( n = 413 ) . RESULTS There was an 18 % reduction in the risk of death for patients treated with pegylated liposomal doxorubicin ( median survival 62.7 weeks for pegylated liposomal doxorubicin and 59.7 weeks for topotecan-treated patients ; HR = 1.216 ; 95 % confidence interval ( CI ) 1.000 - 1.478 ; P = 0.050 ) . The hazard ratio for all r and omized subjects ( includes those r and omized , but never treated ; n = 481 ) was 1.23 ( median survival 63.6 weeks for pegylated liposomal doxorubicin and 57.0 weeks for topotecan-treated patients ; 95 % CI 1.01 - 1.50 ; P = 0.038 ) . For patients with platinum-sensitive disease , there was a 30 % reduction in the risk of death for the pegylated liposomal doxorubicin-treated group ( median survival 107.9 weeks for pegylated liposomal doxorubicin and 70.1 weeks for topotecan-treated patients ; HR = 1.432 ; 95 % CI 1.066 - 1.923 ; P = 0.017 ) . In patients with platinum-refractory disease , survival was similar between treatment groups . CONCLUSION Long-term follow-up demonstrates that treatment with pegylated liposomal doxorubicin significantly prolongs survival compared with topotecan in patients with recurrent and refractory epithelial ovarian cancer . The survival benefit is pronounced in patients with platinum-sensitive disease", "PURPOSE To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma . METHODS AND MATERIAL S Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were review ed . The indications for radiation therapy , radiation therapy techniques , details , tolerance , and response were recorded . A complete response required complete resolution of the patient 's symptoms , radiographic findings , palpable mass , or CA-125 level . A partial response required at least 50 % resolution of these parameters . The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated . RESULTS The median age of the patients was 67 years ( range 26 to 90 years ) . A median of one laparotomy was performed before irradiation . Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation ( median = 6 cycles ) . The reasons for palliative treatment were : pain ( n = 22 ) , mass ( n = 23 ) , obstruction of ureter , rectum , esophagus , or stomach ( n = 12 ) , a positive second-look laparotomy ( n = 9 ) , ascites ( n = 8) , vaginal bleeding ( n = 6 ) , rectal bleeding ( n = 1 ) , lymphedema ( n = 3 ) , skin involvement ( n = 1 ) , or brain metastases with symptoms ( n = 11 ) . Some patients received treatment for more than one indication . Treatment was directed to the abdomen or pelvis in 64 patients , to the brain in 11 , and to other sites in 5 . The overall response rate was 73 % . Twenty-eight percent of the patients experienced a complete response of their symptoms , palpable mass , and /or CA-125 level . Forty-five percent had a partial response . Only 11 % suffered progressive disease during therapy that required discontinuation of the treatment . Sixteen percent had stable disease . The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months ( median = 9 months ) . The 1- , 2- , 3- , and 5-year actuarial survival rates from diagnosis were 89 % , 73 % , 42 % , and 33 % , respectively . The survival rates calculated from the completion of radiotherapy were 39 % , 27 % , 13 % , and 10 % , respectively . Five percent of patients experienced Grade 3 diarrhea , vomiting , myelosuppression , or fatigue . Fourteen percent of patients experienced Grade 1 or 2 diarrhea , 19 % experienced Grade 1 or 2 nausea and vomiting , and 11 % had Grade 1 or 2 myelosuppression . CONCLUSIONS In this series of radiation therapy for advanced ovarian carcinoma , the response , survival , and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens . Cooperative groups should consider evaluating prospect ively the use of radiation therapy before nonplatinum and /or nonpaclitaxel chemotherapy in these patients", "OBJECTIVE The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer , in which the maximum diameter of residual is suboptimal residual cancer , in which the residual disease is > 1 cm . Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease or = 1 cm has been performed . This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a r and omized trial of intense versus st and ard chemotherapy . STUDY DESIGN Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses , respectively . There was no difference in progression-free interval or survival between the two arms . Of the 458 stage III ( with residual disease > 1 cm ) and stage IV patients entered in this study , 294 stage III patients comprise the current analysis . Surgical reporting forms , operation reports , and pathology reports were review ed to determine initial greatest tumor diameter and residual tumor diameter . Patients were grouped by residual diameter . Multivariate analysis considered residual diameter of disease , age , histologic characteristics , performance status , and ascites . An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group . RESULTS Patients ranged in age from 20 to 80 years , with a median of 60 years . All patients were Gynecologic Oncology Group performance status 0 to 2 . Fifty-two percent had grade 3 tumors , and 39 % and 9 % , respectively , had grade 2 or 1 tumors . All patients had stage III disease . Ninety percent had serous , endometrioid , or mixed epithelial cell type tumors . Multivariate analysis revealed a relative risk of dying as follows : residual disease or = 10 cm , relative risk 1.82 . The difference in survival between those with or = 2 cm residual disease was significant ( p risk of dying between groups with residual disease > or = 2 cm . CONCLUSIONS Among patients with suboptimal ( > 1 cm residual disease ) epithelial ovarian cancer , those who have small diameter residual disease ( < 2 cm ) tend to survive longer than those who have larger residual disease . Among those with larger residual disease , size does not affect prognosis appreciably", "OBJECTIVE A non-r and omized comparison of outcome in women undergoing second-look laparotomy ( SLL ) or clinical follow-up , after receiving six cycles of combination chemotherapy with paclitaxel plus either cisplatin or carboplatin , for optimally resected stage III ovarian cancer . METHODS Prior to chemotherapy r and omization , patients chose whether or not to undergo SLL ; this was a stratification factor to insure balance of treatment assignment . Any subsequent therapy was physician-directed . Explanatory analysis replaced intent-to-treat because of a higher likelihood of detecting SLL effect in the presence of noncompliance . RESULTS There were 393 patients ( median age : 54 ) who Elected SLL and 399 ( median age : 59 ) who Elected No SLL . The former group was more likely to have gross residual disease at initial surgery than the latter group ( 69 % versus 60 % , respectively ) . In the Elected SLL group , 59 ( 15 % ) patients subsequently refused surgery , in nine ( 2 % ) surgery was contraindicated , and 31 ( 8 % ) relapsed or died prior to the procedure . Cancer was found in 46 % of 294 ( 75 % ) patients undergoing SLL . Since early failures ( prior to SLL ) do not address benefit , such patients ( SLL : 32 ; No SLL : 33 ) , defined as progression-free survival ( PFS ) adjusted relative risk of progression is 0.89 ( 95 % confidence interval : 0.75 , 1.07 ) ; the difference in median PFS is 1.0 month ( SLL : 23.9 months ; No SLL : 22.9 months ) . The survival rate curves are superimposable . CONCLUSION In the context of a non-r and omized comparison , the performance of a SLL was not associated with longer survival", "Objective : To report and evaluate a conservative and individualized treatment policy in a homogeneously selected series of patients affected by pure ovarian immature teratoma . Methods : This prospect i ve trial , with specific treatment policies according to stage and grade , was planned and started in 1982 . The study population consisted of 32 patients affected by pure immature teratoma , with the exclusion of mixed germ cell tumors . Fertility-sparing surgery was performed whenever possible . Surgery alone , with careful follow-up , was adopted for stage I or II according to the International Federation of Gynecology and Obstetrics ( FIGO ) and grade 1 or 2 tumors . The other patients , with stage III or with grade 3 stage I or II tumors , or those referred at relapse , were treated with platinum-based chemotherapy regimens . Results : Thirty of 32 patients underwent fertility-sparing surgery . Ten of 32 patients received chemotherapy after surgery , either as adjuvant treatment or in the presence of visible tumor . All 32 patients are alive and disease-free , with a median follow-up from surgery of 47 months ( range 11–138 ) . In six patients , regardless of the administration of chemotherapy , the tumor either spontaneously differentiated toward mature glia or increased in volume , mimicking progression but still remaining completely mature . Five of six patients wishing to procreate had a total of seven normal pregnancies . Conclusions : Pure ovarian immature teratoma is a potentially curable disease with a unique natural history . Our data substantiate the hypothesis that low- grade and low-stage tumors do not require chemotherapy , and that a fertility-sparing surgical approach is warranted in all cases", "PURPOSE A large , r and omized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity . In this study , a number of patients crossed over to the alternative drug as third-line therapy , ie , from paclitaxel to topotecan and vice versa . We therefore were able to assess the degree of non-cross-resistance between these two compounds . PATIENTS AND METHODS Patients who had progressed after one platinum-based regimen were r and omized to either topotecan ( 1.5 mg/m(2)/d ) x 5 every 21 days ( n = 112 ) or paclitaxel ( 175 mg/m(2 ) over 3 hours ) every 21 days ( n = 114 ) . A total of 110 patients received cross-over therapy with the alternative drug ( 61 topotecan , 49 paclitaxel ) as third-line therapy . RESULTS Response rates to third-line cross-over therapy were 13.1 % ( 8 of 61 topotecan ) and 10.2 % ( 5 of 49 paclitaxel ; P = .638 ) . Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment . Median time to progression ( from the start of third-line therapy ) was 9 weeks in both groups , and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel , respectively . The principal toxicity was myelosuppression ; grade 4 neutropenia was more frequent with topotecan ( 81.4 % of patients ) than with paclitaxel ( 22.9 % of patients ) . CONCLUSION Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival . We demonstrated that the two drugs have a degree of non-cross-resistance . Thus , there is a good rationale for incorporating these drugs into future first-line regimens", "LBA5007 Background : BEV , a humanized anti-VEGF monoclonal antibody , has shown a progression-free survival ( PFS ) benefit in 2 frontline phase III trials in patients with EOC , PPC and FTC . The therapeutic impact of BEV in combination with carboplatin ( C ) and gemcitabine ( G ) followed by single agent BEV to disease progression ( PD ) was evaluated in this phase III trial in the platinum-sensitive recurrent setting . METHODS Patients had recurrent , platinum-sensitive EOC , PPC or FTC , 1 prior regimen , no prior BEV , ECOG performance status 0 - 1 , measurable disease . Subjects were r and omized to : Arm A : [ IV C ( AUC 4 , Day ( D ) 1 ) + G ( 1,000 mg/m2 D1 and 8) + placebo ( PL ) D1 ] q21D x 6 cycles ( c ) → PL q21D until PD or unacceptable toxicity ( tox ) Arm B : [ CG + BEV ( 15 mg/kg ) D1 ] q21D x 6 c → BEV q21D until PD or tox primary endpoint was investigator assessed PFS ( RECIST ) . Secondary endpoints included objective response ( OR ) , overall survival ( OS ) , duration of response and safety . The design provided 80 % power to detect a 27 % reduction in the hazard of progression or death in Arm B vs A , limiting the overall type I error of 5 % . RESULTS OCEANS enrolled 484 patients ( 242 per arm ) from 4/07 - 1/10 , median follow up of 24 months . BEV plus CG followed by single agent BEV to PD significantly increased PFS compared to CG alone ( HR=0.484 , p ( p OS data is immature with only 29 % of patients having had an event . The safety profile was consistent with other BEV trials . CONCLUSIONS Results show a statistically significant and clinical ly relevant benefit when bevacizumab is added to chemotherapy in patients with recurrent , platinum sensitive EOC , PPC , and FTC . This is the first phase III trial of an antiangiogenic to demonstrate a clinical benefit to these patients . [ Table : see text ]" ]

[ "Fourteen patients with mild to moderate essential hypertension were r and omized , after a baseline placebo period of 4 weeks , to receive the angiotensin converting enzyme ( ACE ) inhibitor quinapril or a placebo . During a 12 week , double-blind phase , the dosage of quinapril was increased from 10 to 40 mg twice daily being doubled every 4 weeks . At the end of the baseline period and of each month of the double-blind phase , 12 h overnight urine collection s were made and morning blood sample s were taken about 12 h after the last dose of medication . During the double-blind phase , blood pressure in the quinapril group ( n = 7 ) decreased from 159 ± 3/105 ± 1 to 141 ± 6/94 ± 2 mm Hg ( mean ± SEM ) . Serum ACE activity and plasma angiotensin II concentration were reduced to 4 ± 1 % and 14 ± 1 % of the pretreatment values , respectively . Neither the plasma concentrations nor the urinary excretions of prostagl and in E2 , 6-keto-prostagl and in F1α ( a prostacyclin metabolite ) , or thromboxane B2 ( a metabolite of thromboxane A2 ) were affected by quinapril . In the placebo group , blood pressure tended to decline but the biochemical variables remained essentially unchanged . These results indicate that prostanoids are not involved in the antihypertensive action of quinapril , the principal effect of which seems to be inhibition of the renin-angiotensin system", "Summary The presence of slightly increased urinary albumin excretion ( UAE ) , even at levels well below levels detectable by an ordinary dipstick , has been suggested as a predictor of cardiovascular morbidity and as a reflection of the degree of overall vascular permeability . The aim of the present investigation was to study the effects of two different antihypertensive drug regimens , an ACE inhibitor and aβ-adrenoceptor antagonist , on the low UAE rate observed in subjects with uncomplicated , mild to moderate primary hypertension . After a 4-week placebo run-in period , 49 patients ( mean age 54 y ) were r and omly assigned in a double blind manner either to further 4 weeks on placebo ( P , n = 15 ) , 8 weeks on lisinopril ( L , n = 17 ; 20 mg/40 mg o. d. ) or 8 weeks on atenolol ( A , n = 17 ; 50 mg/100 mg o. d. ) . The 24-h UAE was measured every second week . At entry and after 4 weeks the glomerular filtration rate and the renal plasma flow were measured . Both drugs lowered blood pressure ( BP ) to a similar extent after 4 and 8 weeks of treatment ; the blood pressures were 160/106 ( P ) , 159/104 ( L ) and 154/103 ( A ) at entry , and 133/83 ( L ) and 134/87 ( A ) at the end of the study after 8 weeks . On entry the 24-h UAE in all patients ranged from 4 to 49 mg ( mean 14.1 mg ) , and it did not differ significantly between groups . After 4 weeks the UAE during 24 h was reduced by approximately one third in the lisinopril-treated group , and by 10 % in the atenolol reated group , whereas it remained unaltered in the group on placebo . After 8 weeks the 24-hour UAE was approximately 20 % lower compared to baseline levels in the lisinopril-treated patients . In the atenolol-treated group the UAE was unaltered compared to baseline . However , none of the changes in the UAE was statistically significant , nor were there any statistically significant differences between the two antihypertensive regimens . Moreover , there were no significant effect of the lisinopril or atenolol treatment on renal function or on renal haemodynamics . It is concluded that in patients with uncomplicated , mild to moderate hypertension both an ACE-inhibitor , such as lisinopril , as well as aβ1-selective adrenoceptor blocking agent , such as", "In a double-blind , parallel-group study , 260 patients with mild to severe essential hypertension were r and omized to treatment with placebo or spirapril at 6 , 12 or 24 mg once daily for 6 weeks . When blood pressures were measured at the end of the dosing interval ( trough ) , all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures ( siSBP/siDBP ) which were significantly greater than those observed in placebo-treated patients . There were no relevant changes in resting heart rate in any of the study groups . At the study endpoint , the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg , 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo . In a subgroup of 122 patients , blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure . All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6 - 7 mmHg with placebo . The trough : peak ratios for 6 , 12 and 24 mg all lay between 60 % and 90 % for siSBP and siDBP , indicating that most of the peak effect was maintained at trough . Spirapril was well tolerated ; the adverse event profile was not different from that with placebo , and no dose-related adverse events were observed . ( ABSTRACT TRUNCATED AT 250 WORDS", "Dry cough is a troublesome side-effect associated with certain antihypertensive agents that act by modulating aspects of the renin-angiotensin-aldosterone system . The incidence of dry cough associated with two of these therapies , the novel All receptor antagonist telmisartan and the ACE inhibitor lisinopril , was assessed in a multicentre , r and omised , parallel-group , double-blind , placebo-controlled , 8-week study of 88 patients with mild to moderate hypertension who previously demonstrated ACE inhibitor-related cough . Patients received either telmisartan 80 mg , lisinopril 20 mg , or placebo once daily . Cough incidence , measured at each visit by a self-administered symptom assessment question naire , was significantly higher with lisinopril ( 60 % ) than with telmisartan ( 15.6 % ) or placebo ( 9.7 % ) . A visual analogue scale demonstrated a similar trend for cough frequency . Thus the incidence of cough with telmisartan 80 mg is significantly less than that seen with lisinopril 20 mg and is comparable to placebo ", "1 . We describe an approach involving a smaller , shorter study , leading onto a longer , larger study in which the antihypertensive effects of ascending doses of imidapril , a new ACE inhibitor , were investigated . Both studies were planned prospect ively , assuming a clinical ly useful fall in BP to be 8 mm Hg ( s.d . = 9 ) . The studies included patients with mild to moderate essential hypertension ( baseline sitting diastolic blood pressure ( SDBP ) 95 - 115 mm Hg ) . After a placebo run-in of 2 - 3 weeks patients received either placebo or imidapril 2.5 , 5 , 10 or 20 mg in the 2 week study ( n = 91 ) or imidapril 5 , 10 , 20 or 40 mg in the 4 week study ( n = 162 ) . 2 . The overall mean baseline SDBP was 103.4 mm Hg ( s.d . 0.62 ) in the initial study and 101.5 mm Hg ( s.d . 0.41 ) in the 4 week study . 3 . Compared with placebo , imidapril 10 , 20 and 40 mg significantly reduced SDBP . There was no significant difference between these doses , suggesting that 10 mg achieved maximal ACE inhibition in most patients . The 2.5 mg dose showed no significant effect . The 5 mg dose gave an intermediate effect . In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups , and was not worrying", "In a double-blind , r and omized , cross-over , placebo- and rest-period controlled study with two 4-week treatment periods , we examined the effects of angiotensin converting enzyme ( ACE ) inhibition with fosinopril ( 20 mg/day ) on the postexercise pressor and forearm vasoconstrictor responses to a 60 sec cold pressor test . The results indicate that pressor and vasoconstrictor responses were unaffected by prior exercise , fosinopril , and both interventions combined . Expression of the responses as percent change from baseline levels provided identical results indicating that changes in baseline values did not mask an altered vascular responsiveness . It is concluded that skeletal muscle vascular responsiveness to sympathetic nervous activity is unchanged after exercise or during ACE inhibition with fosinopril", "Co-administration of antihypertensive drug therapy and hormonal replacement therapy ( HRT ) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy . The present study was design ed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive , postmenopausal women on HRT . After a 4-week placebo run-in phase , 95 postmenopausal women ( 35–74 years of age ) who had a sitting diastolic blood pressure ( BP ) of 95–114 mm Hg and were treated with HRT were r and omised to a 12-week treatment with moexipril 15 mg or placebo . Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides , total cholesterol , HDL , LDL , total cholesterol/HDL ratio and glucose . Adverse events were recorded continuously . After 12 weeks of treatment , moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo ( −12.2/ −9.9 mm Hg vs −1.6/−4.3 mm Hg , P 0.001 ) . metabolic parameters were not affected by treatment with moexipril : mean levels of triglycerides , total cholesterol , hdl , ldl , total cholesterol/hdl ratio and glucose remained unchanged throughout the study . fibrinogen , an independent cardiovascular risk factor , increased after placebo ( + 35.0 mg/dl ) and decreased after treatment with moexipril ( −33.6 mg/dl ) , the difference , however , was not statistically significant . moexipril was well-tolerated by postmenopausal women using hrt . the most frequent adverse events included headache ( 21.3 % ) , cough ( 12.8 % ) and rhinitis ( 10.6 % ) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups . this study indicates that moexipril is effective and well tolerated in the treatment of hypertensive , postmenopausal women and can safely be co-administered to hrt", "Cilazapril ( CLZ ) is a new , long-acting nonsulfhydril converting enzyme inhibitor ( ACE-I ) . Its effect on peak and trough sitting diastolic blood pressure ( SDBP ) was studied in a total of 85 patients with uncomplicated , essential hypertension at three centers . After 4 weeks of a single-blind placebo ( PLA ) run-in period , patients whose SDBP was between 100 and 115 mm Hg , were r and omized into active treatment with either PLA ( n = 27 ) , CLZ 2.5 mg ( n = 29 ) , or CLZ 5 mg ( n = 29 ) once daily in a double-blind fashion for another 8 weeks . At the end of the PLA run-in and after 4 and 8 weeks active therapy , an hourly blood pressure ( BP ) profile during 1–10 and 21–24 h postdose was performed . The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinical ly significant for both CLZ doses in comparison with the PLA group . The peak/trough ratio after substraction of the PLA effect was 62 % for CLZ 2.5 mg and 59 % for CLZ 5 mg . These results indicate that the dose regimen of CLZ 2.5–5 mg once daily is adequate and effective for 24", "Two hundred and eleven patients with mild or moderate hypertension , mean age 53.5 + /- 9.5 years ( range 24 - 70 ) were r and omised double-blind to treatment with either captopril 50 mg ( C50 ) , hydrochlorothiazide 25 mg ( HCTZ 25 ) , the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg ( C50/HCTZ 25 ) or placebo . Blood pressure , heart rate , body weight and side effects were assessed at the end of the run-in period on placebo and after 4 , 6 , 8 weeks treatment at the same time , 20 - 24 h after the last dosing . Routine biochemical examinations were carried out on all patients after the placebo period as well as after 4 and 8 weeks . Blood pressure significantly decreased in all groups , but the mean percentage change from baseline was highly statistically significant at 8 weeks , for C50 and C50/HCTZ 25 groups . The incidence of clinical side effects was low and not statistically different for the four groups with few specific adverse effects ( one transient alteration of taste in captopril group ) . No patient was withdrawn from the study due to side effects . A better anti-hypertensive efficacy was obtained with the fixed combination captopril 50 mg/hydrochlorothiazide 25 mg once daily compared to placebo or each component alone , and without any difference in side effects", "AIMS To assess the effect of tr and olapril ( 2 mg once daily ) and indomethacin ( 25 mg three times daily ) , alone and in combination , on renal function and renal functional reserve in hypertensive patients ( DBP 95 - 115 mmHg ) requiring regular non-steroidal anti-inflammatory drugs ( NSAIDs ) . METHODS R and omized , double-blind , placebo-controlled , four way crossover design . After 3 weeks treatment renal plasma flow ( RPF ) and glomerular filtration rate ( GFR ) were measured using the p-aminohippurate ( PAH ) and inulin methods . Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1 ) and 10 % amino acid solution . RESULTS There was no significant difference in RPF between treatments : -22.79 ml min(-1 ) ( 95 % CI -54.82 , 9.24 ) for placebo and tr and olapril , -10.37 ml min(-1 ) ( 95 % CI -30.7 , 9.96 ) for placebo and indomethacin , -14.78 ml min(-1 ) ( 95 % CI -50.33 , 20.77 ) for placebo and tr and olapril with indomethacin . There was no significant difference in functional reserve RPF between treatments : -34.96 ml min(-1 ) ( 95 % CI -119.8 , 49.88 ) for placebo and tr and olapril , 29.78 ml min(-1 ) , -15.18 , 74.74 ) for placebo and indomethacin , and -25.84 ml min(-1 ) ( 95 % CI -87.62 , 35.94 ) for placebo and tr and olapril with indomethacin . There was no significant difference in GFR between treatments : -1.01 ml min(-1 ) ( 95 % CI -7.45 , 5.42 ) for placebo and tr and olapril , -7.88 ml min(-1 ) ( 95 % CI -15.08 , -0.68 ) for placebo and indomethacin , and -0.36 ml min(-1 ) ( 95 % CI -7.58 , 6.86 ) for placebo and tr and olapril with indomethacin . There was no significant difference in functional reserve GFR between treatments : 5.13 ml min(-1 ) ( 95 % CI -4.97 , 15.23 ) for placebo and tr and olapril , 6.31 ml min(-1 ) ( 95 % CI -1.88 , 14.5 ) for placebo and indomethacin , 7.21 ml min(-1 ) ( 95 % CI 1.26 , 13.16 ) for placebo and tr and olapril with indomethacin . CONCLUSION In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR", "The efficacy of once-a-day cilazapril ( a new long acting converting enzyme inhibitor ) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated . Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were r and omly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25 , 2.5 or 5.0 mg/day for a further four weeks . At the end of weeks 4 and 8 , systolic and diastolic blood pressures and heart rates were recorded , supine and st and ing , at 0 , 2 , 4 , 6 , 9 , 12 and 24 h following a single dose of drug . At the same times , blood was withdrawn for determination of plasma renin activity and aldosterone . Supine and erect systolic and diastolic blood pressures were lowered to normotensive levels with an optimal response being achieved at a dose of 2.5 mg/day . Supine and erect heart rates were unchanged with respect to drug dosage , and the reflex increase in heart rate and diastolic blood pressure on changing from supine to erect posture was maintained in all groups . Maximum antihypertensive efficacy was from 2 to 6 h after drug ingestion . There were no changes in resting aldosterone , but plasma renin activity was increased at all drug dosages . A single 2.5 mg dose of cilazapril provides blood pressure control for a 24 h period . Cilazapril does not appear to interfere with the reflex autonomic responses to postural change", "Summary The aim of the study was to evaluate whether the combination of ketanserin with captopril exerts an additive antihypertensive effect , as compared with single drug treatment . Twelve patients with uncomplicated moderate essential hypertension received , according to a r and omized , double-blind , crossover design , ketanserin ( 40 mg twice daily ) , captopril ( 50 mg twice daily ) , the combination of the two drugs at these dosages , and the corresponding placebo , each treatment being given for 1 month . Both ketanserin and captopril as monotherapy similarly and significantly reduced blood pressure as compared with placebo ( p ketanserin plus captopril further and significantly reduced blood pressure when compared with single drug treatment ( p blood pressure was normalized were significantly greater under the combined treatment than under ketanserin or captopril monotherpy ( p ketanserin plus captopril exerts a clear additive antihypertensive effect when compared with each treatment as monotherapy , a finding that suggests this combination can be usefully employed in the treatment of hpertensive patients", " Perindopril erbumine , a new long‐acting , non‐sulfhydryl‐containing angiotensin converting enzyme inhibitor , was evaluated in 289 patients with hypertension in a 16‐week , double‐blind , placebo‐controlled dose‐ranging study . After 4 weeks of single‐blind placebo treatment , patients with supine diastolic arterial pressures from 95 to 114 mm Hg were r and omized to receive placebo , 4 mg perindopril once daily , or 2 mg perindopril twice daily . The daily dose of perindopril was increased by 4 mg every 4 weeks to a maximum of 16 mg per day . Mean decreases in systolic and diastolic arterial pressure were greater with perindopril than with placebo ( p in arterial pressure reduction or in the percentage of responders between once‐ and twice‐daily administration of perindopril . Adverse reactions with perindopril were generally mild and , with the exception of cough , were similar with placebo . The findings of this study indicate that perindopril is effective , well tolerated , and suitable for once‐daily administration for the treatment of hypertension", "We compared the effects of angiotensin-converting enzyme inhibition with quinapril to those of selective beta-blockade with atenolol and calcium channel blockade with verapamil in 10 hypertensive subjects in a r and omized double-blind placebo-controlled crossover study . All antihypertensive agents reduced baseline mean arterial pressure equally and did not modify forearm vascular resistance compared to placebo . In response to sustained h and grip exercise , both quinapril and verapamil , but not atenolol , attenuated the pressor response . However , verapamil was associated with an exaggerated increase in forearm vascular resistance during h and grip , whereas quinapril did not alter this response compared to placebo . It is concluded that quinapril and verapamil reduce the pressor response during isometric exercise by quantitatively different effects on the vasoconstrictor response in , as well as outside of , skeletal muscles", "Clinical studies indicate that the angiotensin-converting enzyme inhibitor quinapril is an effective antihypertensive agent when administered once daily . At the end of a 4-week , double-blind crossover trial comparing quinapril and placebo , patients were admitted for a hemodynamic profile study 12 hours after taking the previous dose . A final 20 mg dose of quinapril had no additional effect on blood pressure . This is interesting inasmuch as the plasma half-life of the active metabolite quinaprilat is approximately 2 hours and the effective accumulation half-life is approximately 3 hours . The blood pressure reduction in patients with mild hypertension receiving long-term quinapril therapy may be more closely related to prolonged angiotensin-converting enzyme inhibition or to an effect on tissue angiotensin II concentration than to the plasma half-life . This may be the case particularly for cardiac output and renal circulation , because quinapril lowers total vascular resistance without increasing cardiac output or disturbing autoregulation of renal blood flow . Reduced ventricular wall stress , improved diastolic function , and lower renal perfusion pressure may spare cardiac function and glomeruli from hypertensive vascular damage", "1 . The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril ( 2.5 mg ) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine ( 5 mg ) were assessed in a double-blind , double dummy placebo controlled , r and omised , crossover study in 20 patients ( mean age 55.4 years ; range 46 - 69 ) with uncomplicated mild to moderate hypertension ( supine diastolic > 90 mmHg placebo ) . The four r and omised , double-blind , crossover study phases evaluated the response to 4 weeks of once daily treatment with placebo , monotherapy with each drug and the combination . Noninvasive ambulatory blood pressure monitoring ( Spacelabs 90207 ) was performed for 24 h at the end of each phase . 2 . The mean 24 h ambulatory blood pressure ( mmHg ) was 147.9/92.0 following placebo , 141.3/87.8 following monotherapy with ramipril 2.5 mg , 136.8/85.8 following monotherapy with felodipine ER 5 mg and 131.1/82.6 following the combination of ramipril 2.5 mg and felodipine ER 5 mg . All active treatment phases significantly reduced mean 24 h ambulatory diastolic pressure by comparison with placebo . The antihypertensive efficacy of the combination was additive . 3 . The coadministration of ramipril did not attenuate the incidence of headache attributable to felodipine ER", "The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme ( ACE ) inhibitor ( cilazapril ) on both office and ambulatory blood pressure ( BP ) levels in free living subjects with elevated BP . The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly . After exclusions , 39 subjects ( 24 men , 15 women , aged 28 - 65 years ) with mildly to moderately elevated BP completed the study . After 3 months run-in period with placebo ( first month on normal-salt and the next 2 months on sodium-restricted diet ) the subjects were r and omised into either salt-restriction placebo or salt-restriction cilazapril ( 2.5 mg daily ) groups for 3 months . In the whole group , 24-h urinary sodium excretion decreased ( mean + /- s.d . ) from 198 + /- 60 to 112 + /- 59 mmol ( 4 weeks vs 24 weeks , P Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase ( -7.1 [ 95 % Cl -11.2 ; -3.0 ] and -4.2 [ 95 % Cl -6.6 ; -1.8 ] mm Hg for systolic and diastolic BP ) , and similarly the daytime ambulatory BP ( ABP ) was reduced during this period ( -2.8 [ 95 % Cl -5.2 ; -0.5 ] and -2.8 [ 95 % Cl -4.5 ; -1.2 ] mm Hg , systolic ( SBP ) and diastolic blood pressure ( DBP ) respectively ) . No changes were observed in the night time ABP . Addition of cilazapril to sodium-restriction enhanced significantly the office BP ( -13.2 , [ 95 % Cl -20.2 ; -6.2 ] , and -9.1 [ 95 % Cl -13.5 ; -4.7 ] ) and daytime ABP ( -5.9 , [ 95 % Cl -10.1 ; -1.8 ] and -5.3 , [ 95 % Cl -8.8 ; -1.9 ] ) reduction . Blood glucose , plasma insulin or serum lipids did not change during the study . Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension . The antihypertensive effect of cilazapril could be enhanced by sodium restriction", "Objective To compare the antihypertensive efficacy and systemic tolerability of valsartan , a new angiotensin II receptor antagonist , with placebo and with an angiotensin converting enzyme ( ACE ) inhibitor , enalapril . Design A total of 348 adult out patients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind , parallel , study . Patients were allocated r and omly in a ratio of 2:2:1 to receive 80 mg valsartan once a day , 20 mg enalapril once a day , or placebo for 8 weeks in general practice . Patients were assessed at 4 and 8 weeks of therapy . Main outcome measures The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure ( SDBP ) after 8 weeks of therapy . Secondary variables included the change in sitting systolic blood pressure ( SSBP ) and response rates at 8 weeks . Results Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo . Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of — 9.5mmHg for valsartan and — 9.4mmHg for enalapril ( 4.5mmHg for placebo ) . No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP . Response rates at 8 weeks were significantly greater for valsartan ( 54 % ) and enalapril ( 58 % ) than for placebo ( 20 % ) , with no significant difference between the two active treatments . Both valsartan and enalapril demonstrated a consistent a nti hypertensive effect over time , with 90 % of patients with a response at 4 weeks responding at 8 weeks . Both of the treatments were tolerated well . Although the incidence of coughing was generally low in the study , more cases were reported with enalapril ( three ) than with valsartan ( one ) or placebo ( none ) . Conclusions The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension . Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing", "In order to evaluate the antihypertensive effect and the tolerability of combination therapy with an angiotensin converting enzyme inhibitor ( captopril ) and a dihydropyridine calcium antagonist ( nifedipine ) compared with monotherapy and placebo , we studied 32 uncomplicated essential hypertensives . At the end of a 1-month placebo washout period , their diastolic blood pressure was > 105 and The subjects then received , according to a double-blind r and omized crossover design , captopril ( 50 mg twice daily ) , nifedipine ( 20 mg twice daily ) , captopril plus nifedipine at the same doses and the corresponding placebo , each treatment being given for 1 month . Both captopril and nifedipine significantly reduced mean blood pressure , which was further and significantly reduced by the combination of the two drugs . The decreases in mean blood pressure induced by nifedipine were significantly greater than those induced by captopril , and those induced by the combined therapy were significantly greater than those induced by either drug on monotherapy . The heart rate was significantly increased only by nifedipine , and to a similar , but not significant , extent by the combination therapy . Plasma renin activity was similarly and significantly increased and urinary aldosterone tended to decrease to a similar extent under the three active treatments . Adverse effects were mild to moderate in intensity ; their incidence under captopril was lower than that under placebo , while the incidence under nifedipine and combined therapy was greater than under placebo . Ankle oedema disappeared under the combined therapy in three out of four patients who developed this side effect under nifedipine , although one additional patient developed ankle oedema under combination therapy . These data indicate that : ( 1 ) captopril and nifedipine are effective antihypertensive drugs with a balanced cost-benefit ratio , since even if nifedipine alone was more effective in reducing blood pressure , it was less well tolerated than captopril ; ( 2 ) the combination of captopril and nifedipine exerted an additive antihypertensive effect without aggravating , and possibly even reducing , the incidence of adverse effects due to nifedipine . These findings confirm that the association of an angiotensin converting enzyme inhibitor with a dihydropyridine calcium antagonist can be useful in the treatment of essential hypertension", "The immediate ( 0 to 24 hours ) and long-term ( 4 weeks ) hypotensive effects of a new long-acting angiotensin converting enzyme inhibitor , ramipril ( HOE 498 ) , as well as adverse effects and tolerance , were evaluated in 34 patients with primary hypertension . Further , effects on serum and urinary aldosterone and circulating angiotensin II concentrations were measured . After short- and long-term administration of 5 or 10 mg of ramipril , the mean blood pressure was significantly lowered compared with placebo . The mean maximum decrease in blood pressure was noted 4 to 8 hours after administration of ramipril once daily . Sustained blood pressure reduction was achieved after 4 weeks of treatment . Serum concentrations of aldosterone and plasma levels of circulating angiotensin II were reduced for up to 12 hours after drug intake , and tended to return to pretreatment levels at 24 hours . Serum angiotensin converting enzyme activity was markedly suppressed for more than 24 hours after a single dose of 5 or 10 mg ramipril . No subjective or objective adverse effects were noted , and the tolerance to the drug was very good", "Objective To identify appropriate dosages of ramipril and hydrochlorothiazide ( HCT ) when given in combination once a day for the treatment of essential hypertension . Design A 2- or 4-week placebo run-in followed by 6-week , double-blind , parallel-group phase : 4 x 3 factorial ( 2.5 , 5 and 10 mg ramipril ; 12.5 and 25 mg HCT ; all six combinations ; placebo ) . Setting Office practice ( 21 centres ) . Patients and participants Patients with mild-to-moderate essential hypertension ( World Health Organization stage I — II ; supine diastolic blood pressure 100—115 mmHg in last 2 weeks of run-in ) : 581 enrolled , 534 r and omly assigned to double-blind therapy and 517 completed . Main outcome measures Reduction in supine and st and ing blood pressure . Results In pairwise comparisons , the combinations of 5 mg ramipril with 12.5 and 25 mg HCT and 10 mg ramipril with 12.5 mg HCT consistently produced significantly greater blood pressure reductions than their respective components . Response surface analyses were performed , and a stairstep model was constructed to characterize the shape of the dose-response surface . The combinations involving 5 and 10 mg ramipril with 12.5 and 25 mg HCT were again more effective than their components . Withdrawals and adverse effects were minimal for all treatments . A large drop in serum potassium was observed on 25 mg HCT , but not on combination therapy . Addition of ramipril appeared to reduce the hyperuricaemic effect of HCT . Conclusions Several dosage combinations of ramipril plus HCT produced significantly greater blood pressure reductions than the monotherapies at the same dosages . Overall , the combination of 5 mg ramipril and 25 mg HCT gave the best mean reduction . Combination therapy with ramipril plus HCT was safe and effective for patients with mild-to-moderate essential hypertension", "The combination of angiotensin converting enzyme ( ACE ) inhibitor and thiazide diuretic has advantages over monotherapy for the treatment of hypertension . Previous study design s have often been inadequate to demonstrate the details of interactions between these antihypertensive agents . This study used a modified 4 x 4 factorial r and omized , double-blind , placebo-controlled , parallel group design to study the efficacy of 17 different doses of fosinopril ( Fos ) , a phosphinic acid derived ACE inhibitor , and hydrochlorothiazide ( HCTZ ) in 550 patients with mild to moderate hypertension . Data from these variables were fit to quadratic response surface models ( QRSM ) using polynomial functions in the doses of the two components . Using QRSM , seated systolic ( SeSBP ) and diastolic blood pressure ( SeDBP ) responses at 8 weeks were predicted for actual doses and interpolated for intermediate doses not studied . Fos and HCTZ alone and in combination produced a dose-related reduction in SeSBP and SeDBP . Using 10 mg Fos + 12.5 mg HCTZ reduced the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same measure 9.1 mm Hg . Coadministration of Fos and HCTZ produced an additive antihypertensive effect . This study of combination agents for hypertension using a factorial design with QRSM accurately predicts dose responses and is a valuable clinical trial methodology", "Objective : To compare the efficacy , tolerability , and safety of once-daily therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg , benazepril 10 mg , and placebo . Design : R and omised , double-blind , placebo-controlled , parallel-group , multicentre trial . Setting : Twenty-two clinical centres , including private practice groups and academic research clinics . Patients : A total of 530 patients between 21 and 80 years of age with essential hypertension were screened for the study , and 454 were r and omised to treatment with amlodipine 5 mg/benazepril 10 mg , amlodipine 5 mg , benazepril 10 mg , or placebo for 8 weeks . Results : Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in sitting diastolic blood pressure than amlodipine 5 mg ( P benazepril 10 mg ( P placebo ( P response rate in the amlodipine 5-mg/benazepril 10-mg treatment group ( 66.4 % ) was better than that observed in the amlodipine 5-mg ( 50.0 % P benazepril 10-mg ( 38.3 % P placebo ( 24.4 % P heart rate among the four groups . The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg ( 1.7 % ) group was somewhat less than that in the amlodipine 5-mg ( 4.5 % ) group . Conclusions : Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and was superior to amlodipine 5 mg , benazepril 10 mg , and placebo in reducing sitting diastolic blood pressure in patients with essential hypertension", "OBJECTIVE A double-blind , placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of tr and olapril , an angiotensin I converting enzyme inhibitor , in the treatment of mild-to-moderate systemic arterial hypertension . METHODS Of 262 patients enrolled in this study , 127 were treated with tr and olapril 2 mg/day for 8 consecutive weeks , and the remaining 135 patients received placebo for the same period of time . Reduction in blood pressure ( BP ) and the occurrence of adverse events during this period were evaluated in both groups . RESULTS Significantly reductions in both systolic and diastolic pressures were observed in patients treated with tr and olapril when compared with those on placebo . Antihypertensive efficacy was achieved in 57.5 % of the patients on tr and olapril and in 42 % of these normal values of BP were obtained . The efficacy of tr and olapril was similar in all centers , regardless of the area of the country . In a subset of 30 patients who underwent ABPM , responders showed a significant hypotensive effect to tr and olapril throughout the 24 hour day . The adverse event profile was similar in both tr and olapril and placebo groups . CONCLUSION Our results demonstrate , for the first time in a large group of hypertensive patients from different regions in Brazil , good efficacy and tolerability of tr and o-lapril during treatment of mild-to-moderate essential systemic hypertension", "This multicenter , placebo-controlled , double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor , enalapril , and the vascular selective calcium antagonist felodipine extended release ( ER ) in patients with essential hypertension . After a 4-week , single-blind placebo baseline period , 707 patients with sitting diastolic blood pressures ( BPs ) in the range of 95 to 115 mm Hg received placebo , enalapril ( 5 or 20 mg ) , felodipine ER ( 2.5 , 5 , or 10 mg ) , or their combinations for an 8-week double-blind treatment period . All doses of enalapril and felodipine ER had a statistically significant ( p both systolic and diastolic BP . The trough to peak ratios for the combinations ranged from 0.63 ( enalapril 5 mg-felodipine ER 2.5 mg ) to 0.79 ( enalapril 20 mg-felodipine ER 10 mg ) and were consistent with effective BP control with 1 dose/day . Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP . Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema ( 4.1 % ) compared to felodipine ER monotherapy ( 10.8 % ) . There were no serious drug-related adverse effects observed during the study . In this trial , the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension", "Because obesity-associated hypertension has unique hemodynamic and hormonal profiles , certain classes of antihypertensive agents may be more effective than others as monotherapy . Thus , we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week , multicenter , double-blind trial in 232 obese patients with hypertension . Patients with an office diastolic pressure between 90 and 109 mm Hg were r and omized to treatment with daily doses of lisinopril ( 10 , 20 , or 40 mg ) , hydrochlorothiazide ( 12.5 , 25 , or 50 mg ) , or placebo . Mean body mass indexes were similar for all patients . At week 12 , lisinopril and hydrochlorothiazide effectively lowered office diastolic ( -8.3 and -7.7 versus -3.3 mm Hg , respectively ; P systolic ( -9.2 and -10.0 versus -4.6 mm Hg , respectively ; P pressures compared with placebo . Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo ( P lisinopril had an office diastolic pressure Responses to therapies differed with both race and age . Neither treatment significantly affected insulin or lipid profiles ; however , plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril ( + 0.31 versus -0.21 mmol/L ; P Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline . In conclusion , lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension . Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics , may have a more rapid rate of response , and may offer advantages in patients at high risk of metabolic disorders", "The effects of inhibiting angiotensin converting enzyme with perindopril and aldosterone with spironolactone were tested in hypertensive patients over fifty . Accordingly , 75 patients with mild hypertension aged 50 to 70 were r and omly divided into three groups for a double-blind 8 week comparison of the actions of placebo , 4 to 8 mg/day perindopril , and 37.5 to 75 mg/day spironolactone . Side-effects caused one patient to withdraw from placebo and one from spironolactone treatment . Mean blood pressure rose by 2.4 mm Hg after placebo but dropped by 7.4 and 8.6 after perindopril and spironolactone ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter blood glucose or plasma potassium , but induced , respectively , variations of -0.09 , 0 , and + 0.34 mmol/L in cholesterol ( P = .04 ) , and -0.02 , -0.05 , and + 0.27 mmol/L in triglycerides ( P less than .01 ) . After the three treatments , changes in angiotensin converting enzyme activity averaged -1 , -6 , and -1 mU/mL ( P less than .01 ) , in active renin -2 , + 18 , and + 28 pg/mL ( P less than .01 ) , and in aldosterone , + 15 , + 8 , and + 95 pg/mL ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter microalbuminuria , but reduced urinary kallikrein activity by 0.9 , 1.8 , and 5.4 mU/mmol creatinine ( P = .04 ) . Although short-term administration of spironolactone raised renin and aldosterone markedly and lipids moderately ( possibly because of volume contraction ) , the present results show that perindopril and spironolactone are both safe and effective for treating hypertension at the age of 50 or older", "This is a r and omised , double-blind , placebo-controlled , four-way crossover study to determine if indomethacin attenuates the hypotensive effect of tr and olapril . Twenty-three hypertensive patients ( diastolic blood pressure ( DBP ) 95 - 115 ) requiring NSAID were recruited . Seventeen completed the study . Three week treatment periods : tr and olapril 2 mg od and indomethacin 25 mg tds , tr and olapril 2 mg and placebo , indomethacin and placebo , placebo and placebo . Clinic and ambulatory BP after 3 weeks of each treatment . Study had 85 % power to detect a 5 mm Hg difference in BP ( s.d . 7 mm Hg ) . End of treatment clinic BPs were : 152.9/98 mm Hg ( 95 % CI 147.2 , 158.6/95.8 , 101.4 ) with placebo and placebo ; 150.4/94.9 mm Hg ( 95 % CI 144.7 , 156.1/92.1 , 97.7 ) with tr and olapril and indomethacin ; 148.2/96.5 mm Hg ( 95 % CI 142.5 , 153.9/93.7 , 99.3 ) with tr and olapril and placebo ; and 156.6/97.4 mm Hg ( 95 % CI 150.9 , 162.3/94.6 , 100.2 ) with indomethacin and placebo . There were no significant interactions between tr and olapril and indomethacin for clinic systolic BP ( SBP ) ( P = 0.79 ) or clinic DBP ( P = 0.87 ) . When tr and olapril treatments ( placebo or with indomethacin ) were compared to treatments without tr and olapril ( placebo or indomethacin ) , tr and olapril lowered clinic SBP by 5.4 mm Hg ( P = 0.047 ) and DBP by 2.3 mm Hg ( P = 0.08 ) . Mean ambulatory BP was : 140.6/88.2 mm Hg ( tr and olapril and placebo ) ; 142.8/89.7 mm Hg ( tr and olapril and indomethacin ) ; 149.6/95.0 mm Hg , ( indomethacin and placebo ) ; 147.7/94.0 mm Hg ( placebo and placebo ) . Compared with placebo , tr and olapril and placebo lowered BP by 6.5/7.5 mm Hg ( P tr and olapril and indomethacin lowered BP by 5.0/5.5 mm Hg ( P = 0.001 , SBP ; P tr and olapril 2 mg lowered clinic SBP and ambulatory BP , but indomethacin did not attenuate this . Indomethacin had no significant effect on either clinic or ambulatory BP . The antihypertensive effects of tr and olapril in this study were modest . Patient selection factors may have contributed to the observed responses , but it seems unlikely from these data that a clinical ly important drug interaction has occurred", "Objectives To compare the antihypertensive efficacy and tolerability of the imidazoline I1 receptor agonist moxonidine , a central ly acting antihypertensive , with the angiotensin converting enzyme inhibitor enalapril . Design An 8-week , double-blind , r and omized , placebo- controlled study involving 140 out patients with mild-to- moderate essential hypertension . Methods Out patients with WHO stage I or II hypertension were enrolled in the study . After a 4-week placebo-controlled stabilization phase patients were allocated r and omly to placebo , 0.2 mg moxonidine once a day or 5 mg enalapril once a day for 2 weeks . Dosages were then doubled to 0.4 mg moxonidine once a day or 10 mg enalapril once a day for a further 6 weeks . Blood pressure responses to therapy were measured by conventional office techniques and by 24 h ambulatory blood pressure monitoring . Results The mean reduction in sitting blood pressure with moxonidine was similar to that with enalapril ( 19.5 ± 16.0/12.3 ± 8.7 versus 18.9 ± 13.7/11.8 ± 8.0 mmHg ) and significantly superior to that with placebo ( -4.6 ± 12.3/-4.7 ± 6.8 mmHg , P reducing blood pressure during conventional measurements , moxonidine administration reduced blood pressure throughout 24 h ambulatory measurements . The trough : peak ratio for moxonidine was 0.7 . Both moxonidine and enalapril were tolerated well . Conclusions Moxonidine is an effective and well- tolerated antihypertensive , at least as good as other established forms of antihypertensive medication . The trough : peak ratio of 0.7 indicates that the drug will be effective administered once a day", "Thirteen patients with mild hypertension ( untreated diastolic blood pressure of 95 to 114 mmHg ) received , in r and om order , three successive treatments of four weeks with placebo , spirapril ( 6 mg daily ) , or hydrochlorothiazide ( HCT2 ) ( 24 mg daily ) . At the end of each treatment , blood sample s for assessment of platelet aggregation and platelet release of platelet factor 4 ( PF4 ) and for assessment of fibrinolysis , estimated by tissue plasminogen activator ( t-PA ) , plasminogen activator inhibitor-type 1 ( PAI-1 ) , and euglob ulin clot lysis time ( ECLT ) , were taken , first at rest , then immediately after five to ten minutes of vigorous exercise , and finally after the subsequent hour of recovery rest . Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2 , the threshold rising to 10 μM as compared with 1.0 with placebo ( P for adenosine diphosphate ( ADP ) aggregation also rose , from 2 μM to 4 ( NS ) . The resting plasma PF4 value fell , although not significantly , during HCT2 treatment from the placebo value of 3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the threshold of either adrenaline or ADP for aggregation of platelets sample d at rest , and the PF4 plasma levels showed no significant reductions at rest . However , during exercise PF4 showed an approximate doubling of the resting value irrespective of therapy . This exercise-induced increase in PF4 was significantly reduced by spirapril as compared with placebo ( P 0.05 ) . ECLT and t-PA did not shift significantly from the placebo level during either therapy . PAI-1 did not change during spirapril therapy , but during HCT2 treatment it fell , although not significantly , to 9.36 IU/mL from 15.91 with placebo ( NS ) . Spirapril and HCT2 did not produce any unwanted side effect on platelet function or fibrinolysis . HCT2 seems to decrease platelet activity at rest , whereas spirapril seems to some extent to decrease platelet activity at exercise", "The antihypertensive effectiveness of twice-daily dosing with the converting enzyme inhibitor , captopril , was examined in a multicenter study of 294 patients ( 181 white , 111 black , two oriental ) with essential hypertension whose supine diastolic blood pressure ( SDBP ) was 95 mm Hg or higher after 4 to 6 weeks of preliminary placebo administration . In this double-blind study , the patients were r and omized into one placebo and three captopril-treated groups : twice-daily placebo ( n = 77 ) or twice-daily captopril 25 mg ( n = 77 ) , 50 mg ( n = 71 ) , or 100 mg ( n = 69 ) . The average decreases in SDBP after 8 weeks of treatment were 5.2 % , 7.7 % , 11.7 % , and 10.5 % , respectively . Only the two higher dose groups differed significantly from the placebo group ; they also differed from the lowest dose group . The proportions of patients classified as having normalized pressures ( SDBP less than 90 mm Hg ) in the four groups were 39 % , 47 % , 70 % , and 50 % . If the results were analyzed by race , all three captopril-treated groups differed significantly from the placebo-treated group in the white patients but not in the black patients . However , direct comparisons between the white and black groups showed a difference only at the low , 25 mg twice daily ( b.i.d . ) , captopril dose . Thus , although conventionally given on a three-times daily basis , the twice-daily ( 12-hourly ) administration of captopril provides effective antihypertensive treatment in doses of 50 or 100 mg b.i.d . Moreover , white patients also exhibit a significant response to captopril at doses as low as 25 mg b.i.d . ( ABSTRACT TRUNCATED AT 250 WORDS", "The objective of the study was to examine the influence of angiotensin converting enzyme ( ACE ) inhibition on circulatory responses to st and ardized stress tests in primary mild to moderate hypertension . Patients ( n = 28 ) received 5 mg ramipril daily or placebo for 6 weeks in a double-blind crossover design , followed by 6 months of open ramipril treatment . Mental stress ( a 20-min Stroop 's color word conflict test ) and a cold pressor test were performed at the end of each of the three study periods . Noninvasive blood pressure and heart rate were recorded . Ramipril reduced systolic and diastolic blood pressure levels at rest ( from 146+/-3/99+/-3 with placebo to 135+/-4/94+/-3 at 6 weeks , and 136+/-4/91+/-3 mm Hg at 6 months , in the laboratory ) and during mental stress . Resting heart rates were unchanged by ramipril . Ramipril reduced systolic blood pressure and heart rate responses during mental stress ; diastolic blood pressure responses were unchanged . Ramipril reduced cardiac workload ( systolic blood pressure x heart rate ) levels and responses . Treatment effects at 6 months were generally greater than at 6 weeks . During the cold pressor test systolic and diastolic blood pressure levels were lowered by ramipril , but responses were unchanged . Heart rate responses , however , were reduced . Thus , ramipril reduced cardiac workload levels and responses also during the cold pressor test . These findings show that ACE inhibitors can reduce cardiac workload during stressful situations . If confirmed , this would seem to offer an advantage in the treatment of hypertension", "BACKGROUND Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period , a time when both morbid and mortal cardiovascular events are increased compared with other times of the day . METHODS We studied the effects of a chronotherapeutic delivery system of verapamil ( controlled-onset extended release [COER]-24 system ) dosed at bedtime versus conventional morning administration of both enalapril and losartan on the blood pressure ( BP ) , heart rate , and the heart rate systolic BP product during the first 4 hours after awakening in a placebo-controlled , forced-titration trial . There were 357 men and women enrolled in the trial with an untreated sitting diastolic BP of 95 to 114 mm Hg and ambulatory daytime diastolic BP > or = 85 mm Hg . Patients were r and omized to either COER-verapamil hydrochloride each evening ( 240 mg titrated to 360 mg ) , enalapril each morning ( 10 mg titrated to 20 mg ) , losartan each morning ( 50 mg titrated to 100 mg ) , or placebo . Early morning assessment s of BP , heart rate , and the heart rate systolic BP product were performed by use of 24-hour ambulatory recordings after 4 weeks ( low dose ) and 8 weeks ( high dose ) of therapy . RESULTS Results were similar at weeks 4 and 8 for all treatment groups except that the magnitude of change was greater at week 8 . After 8 weeks of treatment , reductions in early morning BP by COER-verapamil were significantly greater ( -15/-10 mm Hg ) than enalapril ( -9/-7 mm Hg , P losartan ( -8/-5 mm Hg , P COER-verapamil also led to greater reductions in morning heart rate , the rate-pressure product , and the rate-of-rise of BP compared with the other 2 active treatment groups . Reductions in mean 24-hour BP were greater in patients treated with COER-verapamil compared with placebo and losartan , and similar to reductions in patients treated with enalapril . CONCLUSIONS Bedtime administration of an agent design ed to parallel the circadian rhythm of BP and heart rate led to significantly greater early morning hemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning", "To investigate the effects of antihypertensive treatment with the angiotensin-converting enzyme ( ACE ) inhibitor lisinopril on insulin sensitivity and related metabolic variables , the insulin sensitivity index ( SI ) , determined with the Minimal Model Method of Bergman , fasting plasma insulin and glucose concentrations , serum total triglyceride and lipoprotein cholesterol fractions , and blood pressure were assessed in 24 lean , non-diabetic patients with essential hypertension . Following a double-blind , r and omised crossover design , these parameters were measured after a 4-week run-in period , after 8 weeks of lisinopril or placebo , and after an additional 8 weeks on placebo or lisinopril , respectively . Furthermore , the level of physical fitness was estimated using the Conconi bicycle ergometer test . SI was low in this study population ( 5.6 vs 13.3 · 10−4·min−1·mU−1·1−1 in normal lean control subjects ) . It did not differ between the placebo run-in phase , the lisinopril phase , and the placebo crossover phase ( 5.8 , 5.5 , and 5.4·10−4·min−1·mU−1·1−1 , respectively ) . Moreover , during the administration of lisinopril , no significant changes occurred in fasting plasma insulin and glucose , areas under the glucose and insulin curves , glucose disappearance rate , serum total triglycerides , and cholesterol or lipoprotein cholesterol fractions . Heart rate at rest , body weight , and anaerobic threshold remained stable throughout the study . Compliance assessed by pill-counting exceeded 90 % at all visits . These findings demonstrate that the ACE inhibitor lisinopril is neutral with regard to insulin sensitivity , plasma insulin and glucose , and lipoprotein metabolism in patients with essential hypertension", "To assess the efficacy and time-dependent effects of once-daily moexipril , a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme ( ACE ) inhibitor , moexiprilat , we conducted a multicenter , double-blind , placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure ( BP ) recordings . Patients were included in the trial based on a minimum of 40 % of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase ; and the primary endpoint was change in 24-hour ambulatory diastolic BP . Patients were r and omized to receive placebo , 7.5 mg of moexipril , or 15 mg of moexipril once daily . Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy . After the 7.5-mg dose , there were no significant changes in the acute or prolonged clinic BPs compared with placebo . Compared with adjusted mean changes for placebo , the 15-mg moexipril dose lowered clinic systolic BP , but not diastolic BP . In contrast , acute ( 1 day ) reductions in 24-hour diastolic BPs were -2/-3 mm Hg , -6/-4 mm Hg , and -14/-9 mm Hg on placebo , 7.5 mg of moexipril , and 15 mg of moexipril , respectively ( P 24-hour diastolic BPs were 1/-2 mm Hg , -6/-4 mm Hg , and -12/-9 mm Hg for the respective treatment groups ( P < .01 for the 15-mg dose ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Summary The pharmacodynamic effects and acceptability of perindopril ( 4 mg daily ) and hydrochlorothiazide ( 25 mg daily ) given alone or in combination for 1 month were investigated in a double-blind , placebo controlled , parallel group study . The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups . Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide ( 11/7 mm Hg supine ) given alone at these doses . The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure ( 24.5/12.6 mm Hg supine ) taking into account the placebo response . The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide . The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group . Perindopril , whether given alone or in combination with hydrochlorothiazide , was well tolerated and produced no clinical ly significant change in routine haematology or serum biochemistry . The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction", "1 . The role of angiotensin (Ang)II in and the effects of angiotensin‐converting enzyme ( ACE ) inhibitors on the regulation of sympathetic neural activity were examined in humans", "To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor , a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components , with the full-dose monotherapies ( isradipine 5 mg or spirapril 6 mg ) , and with placebo . After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period , 405 patients with a diastolic blood pressure ( DBP ) between 100 and 114 mmHg were r and omly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms . In patients whose blood pressure was not normalized ( defined as DBP≤90 mmHg ) after 6 weeks of treatment , the dosage of either medication was doubled or , in the placebo group , was switched to the fixed combination . After week 6 , the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing ( trough ) for the fixed combination or the monotherapies isradipine 5 mg , isradipine 2.5 mg , spirapril 6 mg , spirapril 3 mg , and placebo were10.4/8.7 , 10.0/9.4 , 6.5/6.7 , 10.0/8.3 , 7.0/5.8 , and 2.2/4.7 mmHg , respectively . The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies , thus showing an additive effect of low-dose isradipine and spirapril . In terms of tolerability , the lowest rate of any adverse events was found in the combination group . In this group , typical adverse events of calcium antagonists , such as headache , flushing , ankle edema , or palpitations , were observed only in 5 % , 2 % , 1 % , and 0 % , respectively , dry cough , considered typical for ACE inhibitors , was observed in only 1 % of the combination group . In conclusion , the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined , exerting a blood pressure – lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the st and ard doses . Thus , low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension", "The responses of forearm bloodflow and heart rate to the Valsalva maneuvre were investigated in patients treated with placebo or cilazapril , a new angiotensin converting enzyme inhibitor . Twenty-four uncomplicated hypertensives , whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo therapy , were r and omly assigned on a double-blind basis to receive either further placebo or cilazapril ( 1.25 to 5.0 mg/day , single dose ) for a further four weeks . At the end of weeks 4 and 8 , each patient performed st and ardized Valsalva maneuvres before and 2 h after the day 's dose of medication . For each maneuvre , forearm bloodflow was measured in the resting phase and at the point of maximum tachycardia during the straining phase , together with a continuous record of heart rate . All patients exhibited the appropriate heart rate response to the maneuvre with marked tachycardia followed by bradycardia on release of straining . There were no differences in the degree of tachycardia , bradycardia or the Valsalva ratio as a result of cilazapril therapy . There were no changes in resting forearm bloodflow as a result of drug therapy but the flow was reduced ( P less than 0.01 ) during the straining period of all maneuvres . The relative decrease in flow during the maneuvre was attenuated ( P less than 0.05 ) in the cilazapril-treated patients at all drug doses but not in those taking placebo . Cilazapril appears to inhibit the sympathetic nervous system response to the baroreceptor stimulation of the Valsalva maneuvre but not the parasympathetic response of heart rate", "The hemodynamic effects of quinapril , a novel nonsulfhydryl‐containing angiotensin‐converting enzyme ( ACE ) inhibitor , were assessed in 10 patients with mild‐to‐moderate essential hypertension . Compared with placebo , quinapril ( 20 mg ) administered twice daily for 4 weeks significantly lowered blood pressure by decreasing total peripheral resistance without producing tachycardia , an increase in cardiac output , or a rise in plasma catecholamines . Quinapril significantly reduced renal , but not forearm , vascular resistance . Renal blood flow , glomerular filtration rate , and filtration fraction remained unchanged . Left ventricular wall stress was markedly reduced by quinapril , but during the relatively short treatment period , only a nonsignificant trend toward reduction in left ventricular mass was observed . These findings suggest that quinapril is an effective antihypertensive agent that lowers peripheral resistance without increasing cardiac output or disturbing autoregulation of renal hemodynamics", "OBJECTIVES To compare the antihypertensive efficacy and tolerability of the imidazoline I1 receptor agonist moxonidine , a central ly acting antihypertensive , with the angiotensin converting enzyme inhibitor enalapril . DESIGN An 8-week , double-blind , r and omized , placebo-controlled study involving 140 out patients with mild-to-moderate essential hypertension . METHODS Out patients with WHO stage I or II hypertension were enrolled in the study . After a 4-week placebo-controlled stabilization phase patients were allocated r and omly to placebo , 0.2 mg moxonidine once a day or 5 mg enalapril once a day for 2 weeks . Dosages were then doubled to 0.4 mg moxonidine once a day or 10 mg enalapril once a day for a further 6 weeks . Blood pressure responses to therapy were measured by conventional office techniques and by 24 h ambulatory blood pressure monitoring . RESULTS The mean reduction in sitting blood pressure with moxonidine was similar to that with enalapril ( 19.5 + /- 16.0/12.3 + /- 8.7 versus 18.9 + /- 13.7/11.8 + /- 8.0 mmHg ) and significantly superior to that with placebo ( -4.6 + /- 12.3/-4.7 + /- 6.8 mmHg , P blood pressure during conventional measurements , moxonidine administration reduced blood pressure throughout 24 h ambulatory measurements . The trough : peak ratio for moxonidine was 0.7 . Both moxonidine and enalapril were tolerated well . CONCLUSIONS Moxonidine is an effective and well-tolerated antihypertensive , at least as good as other established forms of antihypertensive medication . The trough : peak ratio of 0.7 indicates that the drug will be effective administered once a day", "This study evaluated the long-term effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan on the angiotensin-converting enzyme activity in T lymphocytes and plasma in patients with essential hypertension . The study was a r and omized , placebo-controlled , double-blind , crossover design . Nine patients with sitting blood pressure ≥ 95 mm Hg and ≤ 105 mm Hg at the end of a 4-week placebo run-in period entered the double-blind phase of the study , which consisted of three 6-week periods during which patients were treated with placebo , enalapril ( 20 mg , once daily ) , or losartan ( 50 mg , once daily ) The angiotensin-converting enzyme activity in T lymphocytes was measured as the activity of the degradation of the substrate Hippuryl-His-Leu and as the appearance of the dipeptide His-Leu , which was quantified spectrofluorometrically . Enalapril but not losartan suppressed ( p ≤ 0.01 ) the angiotensin-converting enzyme activity in plasma , whereas it stimulated ( p ≤ 0.05 ) the angiotensin-converting enzyme activity in circulating T lymphocytes . Our data document induction of angiotensin-converting enzyme in human T lymphocytes during long-term treatment with the angiotensin-converting enzyme inhibitor enalapril . Angiotensin II receptor type 1 antagonism with losartan had no effect on plasma or lymphocytic angiotensin-converting enzyme ", "Cerebral blood flow ( CBF ) was measured in 13 subjects ( 4 men and 9 women , mean age + /- SD = 63 + /- 7 ) with moderate , uncomplicated and untreated hypertension and 11 normotensive subjects ( 6 men and 5 women , mean age + /- SD = 66 + /- 5 ) . A second CBF measurement was performed in hypertensive subjects after a 60 days r and omized double blind treatment with either captopril , 75 mg a day ( n = 8) or placebo ( n = 5 ) . CBF was quantified using the 133Xe inhalation technic and 16 stationary detectors by hemisphere . Comparison of CBF values between hypertensive subjects before treatment and normotensive subjects demonstrated a decrease of CBF in the hypertensive group ( 49 + /- 9 vs 72 + /- 14 ml/100 g/min ; p captopril group showed a significant fall in systolic ( p diastolic ( p blood pressure and a significant increase in CBF ( 60 + /- 14 vs 49 + /- 11 ml/100 g/min ; p placebo group there was no change in blood pressure and CBF ( Table ) . [ Table ; see text ] Our results demonstrate a decrease in CBF of uncomplicated and untreated elderly hypertensive subjects . This decrease is reversible under chronic treatment with captopril ", "Ramipril is a new , potent nonsulfhydryl inhibitor of angiotensin converting enzyme . The magnitude and duration of its antihypertensive effect were evaluated in a multicenter , placebo‐controlled , r and omized clinical trial conducted in 100 patients with mild to moderate essential hypertension . Ramipril significantly reduced both supine and st and ing blood pressures measured 24 h after dosing . Automated blood pressure monitoring showed that ramipril significantly reduced systolic and diastolic pressures for 24 h after dosing . The peak effect occurred between 3 and 6 h after dosing , with approximately 50 % of this effect retained after 24 h. Ramipril was well tolerated ; there was no significant difference between active drug and placebo in the overall incidence of side effects . Ramipril is an effective and well‐tolerated antihypertensive agent , which reduces both supine and st and ing blood pressure over the entire 24‐h period after dosing", "The new angiotensin converting enzyme inhibitor enalapril ( MK-421 ) , was given in a single daily dose of 20 mg to 53 patients with uncomplicated essential hypertension . Its effects were compared with those of a placebo given to 47 patients on a double-blind r and omized basis . The blood pressure was measured in all patients by a physician , using a mercury sphygmomanometer , and by an automatic device in the absence of the physician . After 15 days of treatment , enalapril induced a significant reduction in systolic blood pressure ( 161.4 + /- 13 versus 145.1 + /- 15 , p less than 0.001 ) and in diastolic blood pressure ( 103.3 + /- 6 versus 92.9 + /- 8 , p less than 0.001 ) measured by the physician . The magnitude of the fall in blood pressure was identical after 30 days of active treatment . The reduction in blood pressure induced by enalapril was similarly detected by both methods of measurement , despite the fact that blood pressure values were higher when measured by the physician . A placebo effect was observed with the physician 's values that was not present with the automatically recorded values . A very significant correlation between blood pressure values obtained by these two methods was observed . However , among nine of 53 patients treated with enalapril , a difference in the decrease of blood pressure of 10 mm Hg or more was noted between the two methods of measurement . The decrease in blood pressure occurred with no change noted in the pulse rate or orthostatic hypotension . Plasma renin activity increased after treatment . No changes were observed in creatinine clearance and plasma electrolyte levels", "Despite a marked reduction in cardiovascular morbidity and mortality , treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects . Mild hypertension is often associated with other , usually chronic , diseases . The failure of first-line antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis . This possibility has been addressed in an ongoing trial of novel design , the Perindopril Therapeutic Safety Study , a multicenter , double-blind , r and omized and placebo-controlled trial to determine the safety , efficacy , and interaction of angiotensin-converting enzyme ( ACE ) inhibition with eight of the most common concomitant diseases and their therapies . A total of 480 male and female patients ( 60 per disease group ) aged 30 - 70 years , with a diastolic pressure of 90 - 104 mm Hg , were included after a 3-week placebo run-in if they satisfied st and ard criteria for any of the following : hyperlipidemia , type II diabetes , ischemic heart disease , cardiac arrhythmia , peripheral arterial disease , nephropathy with proteinuria , chronic obstructive lung disease , or rheumatoid arthritis . Of these , 460 patients have completed the 6-week double-blind phase ( comprising two assessment s , at 3 and 6 weeks ) , and are currently undergoing assessment s every 3 months over a 1-year follow-up period . The end points include the incidence of progression or improvement in concomitant disease , the incidence of positive or negative interaction between ACE inhibition and concomitant therapy , change in blood pressure , adverse biochemical and hemodynamic reactions , self-reported side effects , and quality of life indices . Interim results for the 6-week double blind phase will shortly be available . However , the desirability and feasibility of conducting a study according to this novel design have already been proved", "The effect of various antihypertensive medications on platelet function is of increasing interest . Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme ( ACE ) inhibitors not containing a sulfhydryl group such as enalapril , lisinopril , and quinapril on platelet function remains unstudied . Therefore , the aim of the present study was to examine the effect of antihypertensive treatment with quinapril , a novel ACE inhibitor not containing a sulfhydryl group , on platelet function . Ten white men ( age range of 32–61 years ) with untreated mild-to-moderate essential hypertension ( supine diastolic blood pressure > 95 mm Hg ) were treated with 4 weeks each of placebo and quinapril in a double-blind , r and omized , crossover design . Quinapril ( 20 mg twice a day ) significantly lowered systolic ( p 0.01 ) and diastolic blood pressure ( p effect on heart rate or plasma catecholamines . No significant change was noted for in vitro platelet aggregation induced by epinephrine , ADP , or collagen . Plasma concentrations of the platelet release factors β-thromboglobulin and platelet factor 4 did not change , nor did the platelet content of norepinephrine , platelet weight ( mg/10 ml of blood ) , circulating platelet count , or platelet size . Thus , as assessed by a broad spectrum of platelet parameters , we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension . These “ platelet-neutral ” properties of quinapril suggest that quinaparil , both from a thromboembolic and a hemostatic point of view , may be a rather safe agent for treatment of hypertension", "In this study we compared the antihypertensive efficacy and tolerability of captopril at 25 mg twice daily , hydrochlorothiazide ( HCTZ ) , 12.5 mg twice daily and placebo in a multicentre , double-blind , r and omized study that included 152 essential hypertensive patients ( 77 males , 75 females , 87 WHO stage I , 65 WHO stage II , aged 69 + /- 4 years , mean + /- s.d . ) . Supine and st and ing blood pressure were similarly reduced by captopril and HCTZ ( P less than 0.01 for both compared with placebo ) . The heart rate did not change . Captopril ( 25 - 30 mg twice daily ) and HCTZ ( 12.5 mg twice daily ) , alone or in combination , maintained their antihypertensive effect during a 24-week single-blind follow-up study . During the follow-up , diastolic blood pressure remained less than 100 mmHg in seven essential hypertensives on placebo , in 45 on captopril and in 25 on HCTZ . Side effects were observed in seven essential hypertensives during placebo ( treatment withdrawn in two ) , in eight during HCTZ and in three during captopril . Serum potassium was reduced ( P less than 0.05 ) and uric acid was increased ( P less than 0.01 ) only during HCTZ . We conclude that captopril and HCTZ have similar antihypertensive efficacy in the elderly ; however , captopril appears to be better tolerated", "Objective : To compare the antihypertensive efficacy of moexipril , a new angiotensin-converting enzyme ( ACE ) inhibitor , to treatment with hydrochlorothiazide ( HCTZ ) . Patients : Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension . Methods : This was a multicentre , placebo-controlled , double-blind study with a parallel group design . Subjects with a sitting diastolic blood pressure ( DBP ) ≥ 95 mmHg were r and omized to monotherapy with placebo , moexipril 7.5 mg o.d . , moexipril 15 mg o.d . or HCTZ 25 mg o.d . for 8 weeks . Results : Throughout the study period treatment with moexipril and HCTZ result ed in significant reductions of DBP compared with placebo , but there were no significant differences between the active treatment groups . At end point the adjusted mean reductions were 10.5 , 8.7 and 10.1 mmHg in the HCTZ , moexipril 7.5 mg and moexipril 15 mg groups , respectively , compared to 3.9 mmHg in the placebo group . Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels . Otherwise , both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group . Conclusion : Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension", "We assessed blood pressure ( BP ) and heart rate ( HR ) responses in a double‐blind , r and omized study comparing cilazapril , a long‐acting , nonsulfhydryl‐group converting enzyme inhibitor , with placebo in 18 patients with mild to moderate ( sitting diastolic BP , 95 to 114 mm Hg ) essential hypertension . The BP and HR parameters were evaluated at rest ( casual , 24 hours after administration ) , during treadmill exercise testing ( Bruce protocol ) , and with 24‐hour noninvasive ambulatory BP monitoring . These assessment s were made after a 4‐week drug washout period and after 8 to 12 weeks of therapy . After 8 weeks of therapy with cilazapril ( mean dose 3.6 ± 0.9 mg/day ) , casual BP decreased 19/11 mm Hg ( p whereas placebo lowered BP by 4/5 mm Hg ( difference not significant ) compared with the baseline period . The casual HR was modestly ( 7 beats/min ) but significantly ( p cilazapril monotherapy . Exercise BP was reduced by cilazapril ( reduction at peak HR , 23/11 ± 10/5 mm Hg ; p and exercise HR was unchanged . Compared with baseline , the duration of exercise was improved with cilazapril but not with placebo ( 1.0 minute vs − 0.2 minute ; p ) . Twenty‐four‐hour mean , awake , and sleep BPs were reduced with cilazapril with the most impressive reduction occurring during the awake period ( 19/12 mm Hg ; p that cilazapril lowers casual , exercise , and ambulatory BP with a modest but significant improvement in exercise time . Thus cilazapril may be particularly effective in the physically active hypertensive patient", "Repeated blood pressure recordings by non-invasive devices are of better predictive value than single measurements in the evaluation of antihypertensive treatment . Such a method has been used to establish the dose-effect relationship of perindopril . After a two-week placebo run-in period , 40 patients with essential hypertension ( age 56.6 + /- 1.5 years , 31 males , nine females ) were treated with placebo or 2 , 4 or 8 mg of perindopril once daily for one month following a r and omized double-blind design . They were included if at least 75 % of diastolic blood pressure recordings , made over an 8 h diurnal period using an automatic blood pressure recorder , were greater than 95 mmHg on placebo . Values ( mean + /- SEM ) before and after treatment were assessed using analysis of variance . These data showed a significantly greater reduction of blood pressure with 4 mg and 8 mg daily doses compared to placebo and the 2 mg daily dose . Such results were not obtained with blood pressure levels recorded by a mercury sphygmomanometer , confirming the value of an automatic blood pressure recorder as a tool in therapeutic trials", "The subjects were 36 hypertensive patients aged 61 to 79 years ( mean , 66 years ) . After a placebo run-in period of one month , each patient was r and omly assigned to two months of treatment with 100 mg of metoprolol , 50 mg of captopril , or 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride daily , or placebo . The doses were doubled if diastolic pressure was above 95 mm Hg after one month of treatment . Blood pressure , heart rate , and physical fitness ( endurance during a st and ard cycle ergometer exercise ) were measured and side effects assessed after each two-month treatment period . Mean blood pressures were significantly lower after treatment with metoprolol ( 154/92 mm Hg ) , captopril ( 157/92 mm Hg ) , and hydrochlorothiazide-amiloride ( 152/91 mm Hg ) than after placebo ( 170/101 mm Hg ) . Heart rate was significantly lower after treatment with metoprolol ( 64 beats/minute ) than after placebo ( 77 beats/minute ) . Exercise endurance was lower after treatment with metoprolol ( 498 seconds ) and hydrochlorothiazide-amiloride ( 519 seconds ) than after placebo ( 529 seconds ) and higher after captopril ( 541 seconds ) . More patients reached the target exercise work load after captopril than after the other treatments . No patients withdrew from treatment because of side effects or abnormal laboratory test results . All three active treatments benefited the elderly hypertensive patients and did not lower their physical fitness . Captopril appeared to be more effective than the other two treatments", "The combination of an angiotensin converting enzyme inhibitor with a calcium antagonist has become a common way of treating patients with essential hypertension who respond insufficiently to monotherapy . This double-blind , r and omized , parallel , placebo-controlled , multicenter , outpatient study evaluated the antihypertensive efficacy and safety of a calcium antagonist ( verapamil SR ) and an angiotensin converting enzyme inhibitor ( tr and olapril ) in patients with mild-to-moderate ( stages I and II ) essential hypertension . Six hundred thirty-one patients were enrolled in this 10-week study . After a 4-week single-blind placebo phase , patients received one of the following daily dosage regimens in a double-blind fashion for 6 weeks : placebo , 4 mg of tr and olapril , 240 mg of verapamil SR , or a combination of 4 mg of tr and olapril and 240 mg of verapamil SR . Trough sitting diastolic blood pressure was lowered by 4.5 mm Hg , 4.3 mm Hg , and 8.1 mm Hg more than placebo in the tr and olapril , verapamil SR , and combination groups , respectively . In the combination group , sitting diastolic blood pressure was significantly lowered ( P tr and olapril group and by 3.8 mm Hg more than in the verapamil SR group . An analysis of the trough-to-peak ratio for sitting diastolic blood pressure revealed values of 0.75 and 0.67 , for the 4-mg tr and olapril and the combination groups , respectively , at end point . The overall incidence of adverse reactions was similar for all treatment groups . In this study the combination of an angiotensin converting enzyme inhibitor and calcium antagonist was well tolerated and more effective than either agent administered alone for the treatment of mild-to-moderate essential hypertension", "To determine the nature of the result ant effect on blood pressure when angiotensin converting enzyme ( ACE ) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension , two r and omized , double-blind , crossover trials were conducted . In each trial there were four treatment phases , each 4 weeks in duration , comprising a 2 X 2 factorial experiment . Twenty-one patients completed the first study in which the effects of enalapril ( 10 mg twice daily ) were compared with hydrochlorothiazide ( 25 mg twice daily ) , with the two drugs in combination and with placebo . All blood pressure parameters were reduced in the three active treatment phases compared with placebo ( P less than 0.001 ) . Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive . Sixteen patients completed the second study which compared the effects of enalapril ( 20 mg daily ) , atenolol ( 50 mg daily ) , the two drugs in combination and placebo . All blood pressure parameters were again reduced in all phases compared with placebo ( P less than 0.001 ) . Enalapril and atenolol were also equally effective , but in combination their hypotensive effects were less than fully additive , with attenuation of the potential additive response by 30 - 50 % . These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination . Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide ( ANP ) concentrations ( P less than 0.01 ) , suggesting that ANP could contribute to the hypotensive effects of these two drug classes", "A factorial design method was applied in this multicentre trial of the angiotensin-converting enzyme inhibitor quinapril hydrochloride ( Accupril ) in combination with the diuretic hydrochlorothiazide ( HCTZ ) to assess the additive effects of the combination versus monotherapy , to characterise the dose-response relationship of each drug in the presence of the other and to determine if quinapril would attenuate the hypokalemic effect of HCTZ . Following a two to four week placebo-baseline period , 460 qualifying patients with a DBP > or = 100 mmHg and were r and omised to an eight week double-blind phase with one of 16 parallel treatments : placebo , one of three doses of quinapril monotherapy , one of three doses of HCTZ monotherapy or one of nine possible corresponding combinations of quinapril and HCTZ . Mean reductions in sitting SBP/DBP at trough with combination therapy ranged from 7.8 mmHg/7.2 mmHg to 19.6 mmHg/15.1 mmHg ( n = 458 ) . Results of the response surface analyses indicate that the effects of the two drugs were additive and that the maximum antihypertensive effect of quinapril in combination with HCTZ within the doses studied is achieved approximately at a dose of 26 mg quinapril and 25 mg HCTZ . The degree of attenuation of the hypokalemic effect of HCTZ was directly related to the dose of quinapril . At 40 mg quinapril , the HCTZ dose-related decreases of serum potassium were not apparent and overall hypokalemic effects were attenuated by quinapril . Thus , the combination of quinapril and HCTZ given once daily provided additive antihypertensive effects of predictable degrees and the addition of quinapril attenuated the hypokalemic effect of HCTZ", "BACKGROUND Endothelin is a powerful vasoconstrictor peptide derived from the endothelium . We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by study ing the effect of an endothelin-receptor antagonist , bosentan . METHODS We studied 293 patients with mild-to-moderate essential hypertension . After a placebo run-in period of four to six weeks , patients were r and omly assigned to receive one of four oral doses of bosentan ( 100 , 500 , or 1000 mg once daily or 1000 mg twice daily ) , placebo , or the angiotensin-converting-enzyme inhibitor enalapril ( 20 mg once daily ) for four weeks . Blood pressure was measured before and after treatment . RESULTS As compared with placebo , bosentan result ed in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg ( an absolute reduction of 5.7 mm Hg at each dose ) , which was similar to the reduction with enalapril ( 5.8 mm Hg ) . There were no significant changes in heart rate . Bosentan did not result in activation of the sympathetic nervous system ( as determined by measurement of the plasma norepinephrine level ) or the renin-angiotensin system ( as determined by measurements of plasma renin activity and angiotensin II levels ) . CONCLUSIONS An endothelin-receptor antagonist , bosentan , significantly lowered blood pressure in patients with essential hypertension , suggesting that endothelin may contribute to elevated blood pressure in such patients . The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation", "Summary : In a double-blind , placebo-controlled , parallel group study , 24 essential hypertensive subjects were r and omised to receive either placebo or 2 , 4 , or 8 mg perindopril . Perindopril , its deesterified metabolite , perindoprilat , and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay ( RIA ) . Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment . Perindopril peak levels were achieved in levels of perindoprilat were achieved more slowly , reaching a maximum level 5–8 h after dosing , and had an elimination t1/2 of 40 h. Levels of the perindopril glucuronide peaked ∼0.5 h later than perindopril , with an elimination t1/2 of ∼2 h. Perindopril , perindoprilat , and its glucuronide conjugate followed linear kinetics in the dose range of 2–8 mg , and there was no evidence of accumulation with chronic dosing . Perindopril 4 and 8 mg produced significant decreases in pre-dose blood pressure ( BP ) with chronic dosing , with maximal decreases occurring 5–7 h after dosing . Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme ( ACE ) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose", "The angiotensin-converting enzyme ( ACE ) inhibitor tr and olapril , a non-sulfhydryl prodrug which is hydrolysed into tr and olaprilat , was studied in 322 hypertensives of African – American descent using a double-blind , r and omised , placebo-controlled , parallel study design . Following 6 weeks of double-blind treatment with placebo or 0.25 to 16 mg/day tr and olapril , an analysis of drug effect on trough blood pressure ( BP ) stratified by age , gender , weight , pre-treatment plasma renin activity , and tr and olaprilat concentration was performed . Two mg was the lowest effective tr and olapril dose , whereas doses above 4 mg did not significantly reduce trough BP . Reduction in BP did not correlate with trough plasma tr and olaprilat concentration . Pre-treatment plasma renin activity was not a reliable indicator of antihypertensive response , as similar reductions in BP occurred even in patients with the lowest renin levels . There were no observable differences based on age , gender or measurements of the renin-angiotensin- aldosterone axis . In conclusion , neither age , gender or plasma renin activity influenced anti-hypertensive response to angiotensin-converting enzyme inhibition in African –", "Angiotensin-converting enzyme ( ACE ) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity ( M ) . However , the evidence for the latter effect does not st and close scrutiny . We have assessed the effect of the ACE inhibitor tr and olapril on M in 16 patients ( mean + /- SD age , 58 + /- 10.6 yr ) with mild-to-moderate essential hypertension ( initial blood pressure , 173 + /- 14.5/93 + /- 8.0 mm Hg ) , obesity ( body mass index , 30 + /- 5.4 kg/m2 ) , and impaired glucose intolerance ( n = 4 ) or type 2 diabetes ( n = 12 ) in a double-blind , placebo-controlled crossover design . All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies ( soluble insulin , 1.5 mU/kg x min ) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg tr and olapril or placebo ( 2-week washout ) . M ( mean + /- SD ) did not change with tr and olapril : placebo ( run-in ) , 5.2 + /- 1.98 mg/kg x min ; placebo , 5.3 + /- 1.70 mg/kg x min ; tr and olapril , 5.1 + /- 1.65 mg/kg x min ; P = 0.58 ; 95 % confidence intervals , -0.74 , 0.43 ( tr and olapril vs. placebo ) ; 95 % power to exclude an 8 % increase in M. In conclusion , tr and olapril had no clinical ly relevant effect on M in patients with hypertension and type 2 diabetes . Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and /or use of surrogate measures of", "BACKGROUND The objective of this study was to compare the antihypertensive efficacy and tolerability of c and esartan cilexetil ( CC ) with that of enalapril ( E ) and placebo ( P ) in hypertensives by clinic and ambulatory blood pressure ( BP ) . PROCEDURES The study was an Italian multicenter , r and omized , double-blind , parallel group trial including 227 mild to moderate essential hypertensives ( age range , 18 to 70 years ) . After 4 weeks of P , patients were r and omized to 8 weeks of treatment with P or CC ( 4 mg ) or E ( 10 mg ) once daily , which was eventually increased to 8 mg and 20 mg once daily in nonresponders . At the end of each study phase , trough BP was measured by conventional sphygmomanometry and ambulatory BP was monitored over 24 h by a Spacelabs device . Analysis of 24-h BP profile included calculation of 24-h , daytime , nighttime , and hourly average values . RESULTS In the 178 patients evaluable per protocol , at the end of 8 weeks of treatment , trough systolic ( S ) and diastolic ( D ) BP were similarly reduced by both active treatments ( 13 + /- 12 and 10 + /- 7 mm Hg for CC and 14 + /- 12 and 10 + /- 7 mm Hg for E ) and significantly more by both treatments than by P ( 6 + /- 11 and 7 + /- 8 mm Hg , P reduction in 24-h BP was again similar for the two active groups . The antihypertensive effect was still evident during h 23 and 24 after the last dose for both active treatments ( 8 + /- 20 v 5 + /- 18 mm Hg for SBP and 4 + /- 12 v 6 + /- 13 mm Hg for DBP , CC v E , respectively ) but not for P. Heart rate was not significantly modified by either active treatment . The incidence of adverse events was greater in the E than in the CC group . CONCLUSIONS Our study provides evidence that CC at a dose of 4 to 8 mg is as effective as E at a dose of 10 to 20 mg over 24 h , but is better tolerated than", "Summary In a double-blind , r and omized , multicenter study the antihypertensive efficacy of cilazapril 5.0 and 2.5 mg once daily vs. placebo was examined on 180 ambulatory hypertensive subjects with supine diastolic office blood pressure ( OBP ) 3 ≥ 95 and ≤ 115 mm Hg : a 4-week , single-blind , placebo period was followed by a 4-week double-blind treatment period . At the beginning and end of the latter , OBP measurements and ambulatory 24-h BP monitoring ( ABPM ) were both carried out on two different days ( 3 ± 1 ) , whereby each time two 24-h BP recordings were made using SpaceLabs 90202 . Measurements were made every 30 min , and actual waking and sleeping phase evaluation was done using diary entries . White coat hypertensive patients were excluded by the ambulatory BP ( ABP ) inclusion criterion : mean diastolic 24-h BP ≥ 85 mm Hg , or frequency of measurements > 90 mm Hg 5 ≥ 35 % . One-hundred eighty patients were included in the study . Safety was evaluated in 170 of these patients , and efficacy on OBP in 162 . Twenty-four-hour BP recordings that were amenable to analysis were available in the case of 146 patients ( average age 56 ± 10 years , 56 women , 90 men ) . The results of the main target variable for OBP , namely responder rates , were in the three treatment groups : placebo , 39.6 % ; cilazapril 2.5 mg , 55.6 % ; and cilazapril 5.0 mg , 65.5 % . All three treatment groups revealed a statistically significant effect ( p the reduction of mean BP values : placebo from 161.6/102.2 to 149.4/94.7 mm Hg , cilazapril 2.5 mg from 162.9/102.1 to 149.7/92.0 mm Hg , and cilazapril 5.0 mg from 158.4/100.6 to 145.6/90.5 mm Hg . In contrast to OBP data , the analysis of the 24-h ABP profile showed a significant global antihypertensive effect on systolic and diastolic mean values only in the case of the two cilazapril dosages ( p The drop in 24-h mean values was as follows : placebo from 148.3/91.7 to 146.1/90.1 , cilazapril 2.5 mg from 151.0/93.3 to 143.6/88.9 , cilazapril 5.0 mg from 148.0/92.2 to 140.8/86.1 . Analysis of the placebo effect using OBP measurement and ABPM led to completely opposing conclusions . In OBP measurement , a highly significant antihypertensive 24-h trough effect is simulated . In 24-h BP , the placebo effect is slight and restricted to a limited time interval ( approximately 8 h ) during the active waking phase . Both cilazapril groups had equipotent antihypertensive effects on systolic BP but distinctly dose dependent effects on diastolic BP . Both dosages demonstrated a continuous BP control , especially during the critical early morning waking-getting-up phase . Cilazapril 2.5 and 5.0 mg once daily was well tolerated", "AIMS The aims of this study were to examine the effects of tr and olapril , a long acting angiotensin converting enzyme ( ACE ) inhibitor with high tissue uptake , on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus . METHODS Insulin sensitivity was assessed after an acute dose ( day 3 ) and 19 days continuous treatment ( days 3 - 21 ) using the isoglycaemic , hyperinsulinaemic glucose clamp with D[3 - 3H ] labelled glucose , a variable D[3 - 3H ] priming dose and a ' hot ' glucose infusion . Rates of glucose appearance ( Ra ) and glucose disappearance ( Rd ) were isotopically determined during the basal and insulin stimulated periods of the clamp . Twenty-four ( 5 female ) hypertensive ( blood pressure > 75th centile for age and sex ) patients with Type 2 diabetes mellitus were studied . Patients were r and omized , in a double-blind manner , to either tr and olapril 4 mg daily ( T ) or placebo ( P ) . RESULTS Baseline ( day 1 ) systolic ( mean + /- SD ; P 164+/-14 and T 168+/-13 mm Hg ) and diastolic ( P 93+/-6 , and T 98+/-10 mm Hg ) blood pressures were comparable . On days 3 and 21 , significant reductions were observed in both groups ( P and olapril-treated group , serum tr and olapril concentrations were > 200 pg/ml on days 3 and 21 , in all patients apart from one subject at a single visit , while tr and olapril was undetectable in the placebo group . Body mass index ( BMI ) was greater in T compared with P ( 32.2+/-5.4 v. 28.3+/-4.6 , P = 0.07 ) . After correcting for BMI , basal hepatic glucose output ( HGO ) P 2.6 ( 95 % CI 2.23 - 3.13 ) and T 1.91 ( 1.33 - 2.51 ) mg x kg(-1 ) x min(-1 ) and clamped HGO P 0.32 ( -0.44 - 1.09 ) and T 0.87 ( 0.40 - 1.34 ) mg x kg(-1 ) x min(-1 ) were similar in both groups . The insulin sensitivity index was comparable in both groups on all days . Total cholesterol concentrations were similar in both groups throughout the study . Triglyceride concentrations were significantly lower in group P 1.38 ( 1.07 - 1.68 ) ; T 2.14 ( 1.70 - 2.58 ) mmol/l , P tr and olapril result ed in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension . These data support the metabolic neutrality of tr and olapril in patients with Type 2 diabetes mellitus and hypertension", "This multicentre , double-blind , parallel-group , placebo-controlled study compared the antihypertensive effects of equal doses of two long-acting angiotensin converting enzyme ( ACE ) inhibitors . After a two-week , placebo run-in phase , 110 patients with mild to moderate hypertension were r and omised to receive 10 mg lisinopril or enalapril , or placebo for 4 weeks . Office BPs were measured at regular intervals throughout the study . Twenty-four hour ambulatory blood pressure ( ABP ) was measured at baseline and after the first and final doses of study drug . Serum ACE activity and aldosterone were obtained concomitantly with each ABP monitoring . Office BP differences from placebo reached ( P less than 0.05 ) or approached ( P less than 0.10 ) statistical significance at all observations for the lisinopril group but were not significant for any observation in the enalapril group and approached significance on two occasions . After four weeks of treatment , ABP analysis revealed that the lisinopril and enalapril groups , when compared with placebo , had similar and significant systolic and diastolic AUC reductions ( P less than 0.01 ) from baseline over the 24 h dosing interval . During the second half of the dosing interval , 13 - 24 h post drug administration , the lisinopril group was significantly different from placebo ( systolic BP , P = 0.002 ; diastolic BP , P = 0.005 ) while the enalapril group was not . Both drugs were well tolerated . The results indicate that monotherapy with 10 mg of lisinopril is as effective as with 10 mg of enalapril , and that ABP monitoring is useful in more precisely depicting the clinical effect of the known pharmacokinetic properties of these two agents", "The efficacy of spirapril , 6 mg once daily , was compared with enalapril , 5–20 mg once daily , in the control of mild-to-moderate hypertension in a placebo-controlled , parallel-group study . A total of 251 patients participated in the study , all of whom underwent a 4-week washout period on placebo . Thereafter , 100 patients were r and omized to spirapril , 6 mg once daily , 101 patients to enalapril , 5–20 mg once daily , and 50 patients remained on placebo . Sitting diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) were measured at 2-weekly clinic visits . Blood pressure profiles during peak and trough plasma drug concentrations ( 2–4 hours and 24 hours postdose , respectively ) were determined at baseline and 4 and 8 weeks after starting the double-blind phase . Compared with placebo , treatment with both spirapril and enalapril result ed in significant reductions ( p > 0.001 ) in DBP and SBP . DBP was reduced to a greater extent with spirapril than with enalapril both at peak ( −17.4 mmHg vs. −14.8 mmHg ) and trough ( −14.7 mmHg vs. −12.4 mmHg ) . Thus , although the trough/peak DBP ratios for spirapril and enalapril were very similar ( 84 % vs. 82 % ) , actual reductions in DBP were different . Spirapril and enalapril treatment result ed in similar reductions in SBP at both peak and trough levels . Both drugs were well tolerated , and there were very few adverse events or changes in hematological or biochemical parameters during the study . In conclusion , spirapril , 6 mg once daily , as the initial and maintenance dose , is at least as effective and well tolerated as enalapril individually titrated", "In 16 patients with essential hypertension the effects of enalapril 20 mg once daily were compared with those of atenolol 50 mg once daily , with the two drugs in combination and with placebo using a double-blind cross-over design with allocation of treatment order by r and omised Latin squares . For each patient there were four treatment phases , each of four weeks duration , which together comprised a 2 x 2 factorial experiment . All blood pressure parameters were reduced in the three active treatment phases compared to placebo ( p less than 0.001 ) . Supine blood pressures ( group means ) were 171/97 ( placebo ) , 147/85 ( enalapril ) , 154/84 ( atenolol ) and 144/78 ( enalapril plus atenolol ) ( S.E.M. + /- 2/+/- 1-ANOVA ) , and st and ing blood pressures were 170/105 ( placebo ) , 146/92 ( enalapril ) , 154/92 ( atenolol ) and 147/86 ( enalapril plus atenolol ) ( S.E.M. + /- 3/+/- 1 ) . In the combination phase there was an additional hypotensive response but the potential fully additive effects of the two agents were attenuated by 30 - 50 % . The mechanism of the attenuated hypotensive effect of the combined agents has not been determined . Plasma atrial natriuretic peptide ( ANP ) concentration was doubled in the presence of atenolol ( P less than 0.01 ) suggesting that ANP may contribute to the hypotensive effect of the beta-blocker", "AIMS To investigate the dose-response relationship and contribution of verapamil SR and tr and olapril given in combination once a day for the treatment of essential hypertension . METHODS A r and omized , double-blind , placebo controlled , factorial , 12 arm parallel group comparison with placebo , verapamil SR ( 120 , 180 mg ) , tr and olapril ( 0.5 , 1.0 , 2.0 mg ) covering all combinations of both drugs . A 4 week placebo run-in period followed by 6 weeks of treatment . Four hundred and fifty-six patients from office practice ( 22 centres ) with mild to moderate hypertension enrolled and 426 with diastolic pressure > or = 100 mm Hg at the end of run-in period were r and omized . Main outcome measures were reduction in sitting systolic ( SBP ) and sitting diastolic ( DBP ) blood pressure . RESULTS The combination of verapamil SR and tr and olapril , particularly verapamil SR 180 mg and tr and olapril 0.5 or 1.0 mg was significantly superior to both monocomponents at the same dose ( P reductions in DBP from baseline to last visit were 14.1 and 16.0 mm Hg , respectively . Response surface analysis provided further evidence that these combinations were optimal for antihypertensive efficacy . All treatments were well tolerated . The incidence of adverse events did not differ significantly between treatment groups ; the profile of adverse events on combination therapy was mild and consistent with that of each monocomponent . CONCLUSIONS All dosage combinations of verapamil SR and tr and olapril produced significantly greater reduction of blood pressure than the monotherapy at the same dosage . However , verapamil SR 180 mg in combination with tr and olapril 1.0 mg was the dosage with the greatest blood pressure reduction and had the greatest effects compared with the monocomponents", "The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo . Patients with uncomplicated essential hypertension ( diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period ) were r and omly allocated to a double-blind , 12-week treatment with either a combination tablet of felodipine and metoprolol ( Logimax ) , 5/50 mg daily ( n = 321 ) , enalapril , 10 mg daily ( n = 321 ) , or placebo ( n = 304 ) , with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed ( diastolic blood pressure remaining > 90 mm Hg ) . The combined felodipine-metoprolol treatment controlled blood pressure ( diastolic enalapril and 30 % for placebo . A dose adjustment was required in 38 % of patients receiving the combination , in 63 % of patients allocated to placebo , and 61 % of enalapril-treated patients . The overall incidence of adverse events was 54.5 % during felodipine-metoprolol treatment ; the corresponding values for enalapril and placebo were 51.7 % and 47.4 % , respectively . Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination , in 10 patients on enalapril , and 12 patients on placebo . No significant change in patients ' well-being was observed in either of the three study groups . These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone . This improved efficacy is obtained without impairing the tolerability . The fixed-dose combination of felodipine and metoprolol , therefore , may become a valuable option to initiate antihypertensive treatment", "The aim of the study was to identify the most appropriate dosage combination of ramipril and felodipine ER ( an extended release tablet ) for mild-to-moderate hypertension . Hypertensive patients ( N = 507 ) with supinediastolic blood pressure ( DBP ) values between 100 - 115 mm Hg were included in a r and omized , multicenter , double-blind study of 3x4 factorial design with a 2 - 4 week single-blind , placebo run-in and 6 week active treatment phase . The patients were r and omized to 12 groups : placebo , ramipril ( 2.5 , 5 , 10 mg ) , felodipine ER ( 5 , 10 mg ) , or ramipril-felodipine ER combinations ( 2.5/5 mg , 2.5/10 mg , 5/5 mg , 5/10 mg , 10/5 mg , 10/10 mg ) . Although the greatest reductions in blood pressure were observed with ramipril-felodipine ER ( 10/10 mg ) , consideration of the antihypertensive efficacy and safety factors suggest that the ramipril-felodipine ER ( 5/5 mg ) combination has the best efficacy/tolerability ratio of the combinations tested . The incidence of adverse events with ramipril-felodipine ER combination therapy was similar to that with felodipine ER monotherapy , but peripheral edema , tachycardia and vasodilatation occurred less frequently with ramipril-felodipine ER ( 5/5 mg ) combination than with felodipine ER monotherapy . The combination of ramipril-felodipine ER ( 5/5 mg ) can be considered to be the most suitable option for hypertensive patients with an inadequate response to either of the monocomponents", "The primary objective of this r and omised , placebo- controlled , double-blind , crossover study , was to evaluate and compare the longer term effects of the angiotensin II type 1 receptor antagonist losartan and the converting enzyme inhibitor enalapril on 24-h ambulatory blood pressure ( BP ) . After a 4-week placebo run-in period , nine patients with essential hypertension entered the double-blind phase of the study , which consisted of three 6-week periods during which patients were treated with placebo , enalapril 20 mg o.d . or losartan 50 mg o.d . Losartan and enalapril , taken between 07.00 and 08.00 , reduced ambulatory BP throughout the 24-h period . Average night time BP was reduced from 133/85 mm Hg on placebo to 124/78 mm Hg on enalapril and to 126/77 mm Hg on losartan . Daytime BP averaged 157/101 mm Hg on placebo , and was significantly lower during enalapril ( 142/91 mm Hg ) than during losartan treatment ( 147/95 mm Hg ) . Clinic BP , measured 2 to 4 hours after drug intake , was reduced to the same extent by both drugs . The losartan-induced BP changes were significantly related to those obtained with enalapril ( 0.63 Ambulatory BP monitoring was repeated after 4 weeks of combined therapy in six patients . The BP lowering effect of the combination was not significantly better than that achieved with enalapril alone . In conclusion , losartan 50 mg o.d . and enalapril 20 mg o.d . lower BP to approximately the same extent , except for a more pronounced effect of enalapril on daytime ambulatory BP . The current study does not provide convincing evidence that addition of losartan to enalapril in the doses used further reduces BP", "1 . Much attention has been given to the effects of various classes of antihypertensive drugs on blood pressure and haemodynamics . The effects of a single bout of exercise on post-exercise blood pressure have also been studied by several investigators . However , the combined effects of prior exercise and antihypertensive medication has drawn less attention . 2 . We examined the separate and combined effects of a single bout of exercise and of angiotensin converting enzyme ( ACE ) inhibition with a new ACE inhibitor ( fosinopril , 20 mg day(-1 ) ) on post-exercise blood pressure and systemic and regional haemodynamics . Ten patients with mild-to-moderate hypertension were studied with a double-blind , r and omized crossover , placebo- and rest period-controlled study design . 3 . At rest , mean arterial pressure ( MAP , -10 + /- 2 mm Hg ) , total peripheral resistance ( TPR , -11 + /- 5 % ) and forearm vascular resistance ( FVR , -17 + /- 8 % ) were significantly ( P MAP ( -3 + /- 1 mm Hg ) , TPR ( -10 + /- 4 % ) and FVR ( -9 + /- 4 % ) were lower after exercise as compared with the control rest period . 5 . During ACE inhibition , MAP ( -3 + /- 1 mm Hg ) and TPR (-8 + /- 4 % ) were lower , but FVR ( + 32 + /- 15 % ) was increased after exercise as compared with the control rest period . 6 . Thus , blood pressure and TPR decreased similarly after exercise during the placebo phase and during ACE inhibition . However , differences in post-exercise forearm haemodynamics during the placebo phase and during ACE inhibition indicate that underlying regional haemodynamics are modified", "Angiotensin-converting enzyme ( ACE ) inhibitors are well established antihypertensives . Their effect on kidney function , however , seems to depend on the pathophysiological mechanisms underlying the clinical symptoms . In one part of the Perindopril and Therapeutic Safety Study ( PUTS ) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril ( Coversum , CAS 82834 - 16 - 0 ) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy . The study was performed as multicenter , r and omized , placebo-controlled , double-blind study . The results show that perindopril reduced blood pressure effectively . The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39 % vs. 21 % in the placebo group . All investigated parameters of kidney function like serum creatinine , creatinine clearance , urinary excretion of albumin and alpha 1-microglobulin remained unchanged during the study . In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion ( perindopril : -292 + /- 205 mg/g creat . vs. placebo : + 61 + /- 48 mg/g creat : p perindopril will not impair kidney function . In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney", "Angiotensin-converting enzyme inhibitors and calcium antagonists are 2 classes of antihypertensive agents frequently used either as monotherapy or in combination . A 6-week , multicenter , r and omized , double-blind , placebo-controlled trial was conducted in essential hypertensive patients ( diastolic blood pressures [ BP ] when seated , 95 - 115 mm Hg ) to evaluate the efficacy , dose response , and safety profiles of enalapril combined with a new once-daily formulation of diltiazem . BP and heart rate were measured at 5 ( peak ) and 24 ( trough ) hours after dose to assess the efficacy and pharmacodynamic profile of the combination given once daily . There were 336 patients r and omly assigned to either enalapril 5 mg plus 1 of 4 dose levels of diltiazem ER ( 60 , 120 , 180 , or 240 mg ) , enalapril 5 mg alone , or placebo . Each combination dose level produced statistically significant reductions ( p trough diastolic BP when seated , compared with placebo ( -6.8 , -8.3 , -10.1 , and -10.3 mm Hg for the diltiazem ER doses of 60 , 120 , 180 , and 240 mg , respectively ) . The 3 highest combination dose levels result ed in statistically significant ( p trough diastolic BP when seated , compared with placebo . There was a significant ( p relation . A trough-to-peak ratio > or = 0.5 was shown for the 3 highest combination doses . Drug-related adverse events were seen in 8.9 % to 19 % of the combination patients , 14.3 % of the enalapril patients , and 8.6 % of the placebo patients . The frequency and type of adverse events were those currently noted with each drug studied when used as monotherapy", "The extent and the duration of the antihypertensive effect of captopril , given once a day at a dose of 50 mg , compared with placebo and with the 100 mg once daily dose was studied in 30 mild or moderate uncomplicated essential hypertensives ( mean ± s.e.m . age 52.0 ± 1.5 years ) , who responded ( mean blood pressure decrease > 10 % ) to a single oral dose ( 12.5 mg ) of captopril . According to a r and omized , double-blind , crossover design , they were given 50 mg captopril four times a day , 100 mg captopril four times a day or matched placebo for 1 month . At the end of each treatment period blood pressure and heart rate were measured every 30 min from 3 h before to 2 h after the last dose . Although the heart rate did not change , mean blood pressure after the 50− and 100-mg doses of captopril was consistently significantly ( P ± 0.05 ) lower than after placebo . The hypotensive effect peaked at the second hour and was still significant 24 h after dosing without any significant differences between the 50− and the 100-mg doses . These findings indicate that captopril , given chronically once a day at a dose of 50 mg to mild to moderate hypertensive responders , exerts its hypotensive effect up to 24 h and that doubling the dose does not increase either the extent or the duration of its action", "A factorial design was applied in this multicenter , double-blind , placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy , to evaluate safety , and to determine the effects on quality of life ( QOL ) of both drugs , alone and in combination . The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure ( BP ) of between 95 mm Hg and 114 mm Hg , after a 4-week placebo washout , were r and omized to one of six treatment groups for 4 weeks of active treatment . Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo . The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure ; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only . The total number of adverse events reported was similar for all six treatment groups . QOL scores were unchanged from baseline and not different between treatment groups . The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone ; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL . Thus , combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy", "The antihypertensive effect of the angiotensin-converting enzyme inhibitor tr and olapril administered in doses of 1 , 2 , and 4 mg/d was compared in 207 white patients and 91 black patients with mild to moderate hypertension following a double-blind , r and omized , placebo-controlled , parallel study design . Tr and olapril is a prodrug that is rapidly hydrolyzed to its active diacid metabolite , tr and olaprilat . After 6 weeks of double-blind treatment , tr and olapril lowered baseline sitting diastolic pressure in both white and black patients . A comparison of the antihypertensive response of the two population s revealed that the black patients required between two and four times the dose of tr and olapril to obtain a response similar to that observed in the white patients . A dose of 1 mg/d tr and olapril result ed in a 6.1 mm Hg mean decrease in baseline sitting diastolic pressure for white patients ; a similar response ( -6.5 mm Hg ) was observed in the black patients at 4 mg/d . In contrast to the population differences in blood pressure , the decreases in angiotensin-converting enzyme activity were similar for both population s. An evaluation of tr and olaprilat levels revealed that there were no racial differences in the tr and olaprilat concentrations required to achieve a given degree of angiotensin-converting enzyme inhibition . Therefore , it appears that the antihypertensive response of black patients is not completely explained by a reduction in angiotensin-converting enzyme activity . The lack of response at a lower dose but increasing response at a higher dose could reflect another vasodepressor activity of tr and olapril or just be evidence of reduced sensitivity of high blood pressure in blacks to angiotensin-converting enzyme inhibition", "The antihypertensive effect and safety of fosinopril and hydrochlorothiazide combined were compared with each drug singly and placebo in a controlled manner . After a 4- to 5-week placebo lead-in period , 67 mild to moderate essential hypertensive patients ( seated diastolic blood pressure £ 95 and £ 110 mm Hg ) were r and omized in a double-blind fashion into four parallel treatment groups : 20 mg fosinopril plus 12.5 mg hydrochlorothiazide , 20 mg fosinopril , 12.5 mg hydrochlorothiazide , and placebo during 8 weeks . Patients were seen biweekly . Sitting diastolic blood pressure was the outcome variable defining therapeutic response . The efficacy of fosinopril plus hydrochlorothiazide as a combined therapy was superior to any single drug ( P hypertension . Mean adjusted systolic/diastolic blood pressure decrements at week 8 were −18.8/−13.7 , −12.9/−11.8 , −8.5/−9.3 , and −2.11−6.9 mm Hg for the fosinopril plus hydrochlorothiazide , fosinopril , hydrochlorothiazide , and placebo groups , respectively . Clinical adverse events and laboratory changes documented throughout the study were similar to placebo and were mild in severity in all groups", "1 In a r and omised study , 475 men with diastolic blood pressures of 92 - 109 mm Hg received either placebo or captopril 37.5 mg , 75 mg or 150 mg/day for 7 weeks . 2 After 7 weeks patients taking placebo were given hydrochlorothiazide 25 mg twice daily , as were two-thirds of each group taking captopril and they were observed for 7 additional weeks . 3 Captopril reduced blood pressure by 12.2 + /- 0.8/9.4 + /- 0.4 mm Hg at 7 weeks ( n = 323 ) and captopril plus placebo reduced it by 10.3 + /- 1.9/10.2 + /- 0.9 mm Hg at 14 weeks ( n = 83 ) ; placebo by 2.0 + /- 1.7/3.4 + /- 0.8 mm Hg ( n = 76 ) ; and captopril plus hydrochlorothiazide by 24.4 + /- 1.1/16.2 + /- 0.6 mm Hg ( n = 173 ) . The effect of low-dose captopril was similar to that of high doses . 4 White patients responded better than blacks , with a blood pressure reduction of 14.7 + /- 1.1/10.7 + /- 0.6 mm Hg ( n = 170 ) v 9.1 + /- 1.2/8.0 + /- 0.7 mm Hg ( n = 151 ) . This difference was abolished by the addition of hydrochlorothiazide . 5 Only 15/384 ( 3.9 % ) of patients were dropped from the study because of adverse effects . 6 The prescription of low-dose captopril might be extendable to patients with mild to moderate hypertension", "Arterial hypertension may be associated with altered left ventricular filling dynamics . The specific goal of this study was to evaluate whether short-term administration of the ACE inhibitor lisinopril in hypertensive patients with an altered diastolic pattern induced an improvement of left ventricular dynamics , assessed by the echocardio-Doppler technique , independently of effects on left ventricular mass . In a double-blind cross-over study 39 essential hypertensive patients with a ratio of peak early to peak atrial velocity ( E/A ) lisinopril ( 20 mg once a day ) and placebo for 4 weeks , respectively . At the end of both the run-in and the treatment periods , blood pressure and heart rate were measured and an echocardio-Doppler examination was carried out . The echocardio-Doppler evaluation was performed both at rest and at the peak of a h and -grip test ( 3 min at 30 % of maximal strength ) . Left ventricular dimensions were obtained from two-dimensionally guided M-mode tracings using the criteria of the American Society of Echocardiography . Left ventricular peak filling rates and filling rate integrals were measured by a pulsed Doppler technique . Lisinopril caused a significant reduction in systolic and diastolic blood pressure at rest ( -13/-9 mmHg vs baseline values , p Lisinopril did not induce any significant change in left ventricular structure and systolic function . All the left ventricular filling parameters considered ( E velocity , A velocity , E/A ratio ) both at rest and during isometric exercise did not significantly differ after lisinopril treatment when compared to those obtained in basal conditions and after placebo administration . This double-blind cross-over study demonstrates that short-term afterload reduction induced by lisinopril does not modify altered diastolic dynamics in hypertensive patients . Diastolic dysfunction of the left ventricle is a complex process influenced by a number of functional and structural factors and apparently can not be significantly improved by short-term blood pressure reduction by antihypertensive therapy", "The safety and efficacy of two fixed dose combinations of enalapril and diltiazem extended release formation ( ER ) ( E/D ) were compared with their monotherapies and placebo in patients with stage 1 to 3 hypertension . The trial design was a multicenter , r and omized , double blind , placebo controlled , parallel group , 12 week treatment phase , followed by a 36 week , open label phase . A total of 891 patients with sitting diastolic blood pressure ( SiDBP ) between 95 and 115 mm Hg were r and omly assigned to enalapril 5 mg , diltiazem ER 120 mg , diltiazem ER 180 mg , enalapril 5 mg/diltiazem ER 120 mg ( E5/D120 ) , enalapril 5 mg/ diltiazem ER 180 mg ( E5/D180 ) , or placebo . In the open label phase , 562 patients received the fixed combination , titrated as needed to control SiDBP Efficacy was determined with trough ( 24 + /- 2 h postdose ) sitting blood pressure measurements at week 12 and at the end of the open label part of the study . Safety was evaluated based on patient symptoms , clinical laboratories , and electrocardiograms ( ECG ) . E5/D120 and E5/D180 significantly reduced trough SiDBP ( -7.6 and -8.3 mm Hg , respectively ; P trough sitting systolic blood pressure ( -7.9 and -9.0 , respectively ; P SiDBP and SiSBP versus placebo . E/D effectively lowered SiDBP and SiSBP during the open label extension . No significant difference was seen among treatment groups for the overall incidence of adverse events . The most common drug related adverse events were headache , edema/swelling , dizziness , asthenia/fatigue , cough , rash , and impotence . The event frequency for the combinations were similar to those seen with the monotherapies . Fixed combinations of E/D were generally well tolerated , with an increased blood pressure lowering effect as compared with the individual components in patients with stage I to III hypertension", "The aim of this study was to evaluate the effects of tr and olapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension . After a washout period of 4 weeks , 42 patients were r and omized to receive 2 mg of tr and olapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks . This was followed by a second washout period of 4 weeks . At the end of each period , clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively , taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night . Two patients were dropped out before any blood pressure evaluation under treatment . Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data ( 2 values per hour during the day and 1 value per hour in the night ) . In the tr and olapril-treated group ( n = 41 ) clinic systolic/diastolic blood pressures were 159.8 + /- 2.0/102.4 + /- 0.8 , 146.8 + /- 2.3/94.8 + /- 1.1 , and 155.7 + /- 2.0/99.2 + /- 0.7 mm Hg in the pretreatment , treatment , and post-treatment periods , respectively . The corresponding values for 24-hour mean blood pressure ( n = 31 ) were 139.5 + /- 1.9/91.2 + /- 1.5 , 131.0 + /- 2.0/84.3 + /- 1.2 , and 139.7 + /- 1.8/90.9 + /- 1.1 mmHg . The differences between the lower treatment , versus the higher pre- and post-treatment , values were all statistically significant ( p < 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride , a new angiotensin‐converting enzyme ( ACE ) inhibitor , for mild‐to‐moderate hypertension . After a 2 to 4 week placebo baseline period , patients with diastolic blood pressure between 95 and 114 mm Hg , were r and omized to receive either placebo or benazepril hydrochloride , 5 , 10 , 20 , or 40 mg , once daily in double‐blind fashion for 28 days . Blood pressure was measured predose and at 1 , 2 , 3 , 4 , 6 , 8 , 12 , 16 , 20 , and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period , and on the first and last day of the double‐blind treatment period ; and 24 hours after the dose at weekly outpatient visits . All doses of benazepril hydrochloride result ed in clinical ly important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose , and following the last dose after 4 weeks of treatment . The findings indicate that benazepril hydrochloride may be clinical ly useful as once‐daily monotherapy in many patients with hypertension", "OBJECTIVE To determine the quality of life ( QOL ) of mild hypertensive patients treated with captopril as compared to placebo . METHODS This is a r and omized , double-blind , placebo-controlled clinical trial held in the out-patient clinic of Zhong Shan Hospital . Adult patients aged from 28 to 75 years with mild hypertension defined as diastolic blood pressure from 90 to 105 mm Hg were the inclusion criteria of the study . There were 278 patients who were eligible to enter the study . They were r and omized to receive captopril or placebo 25 to 50 mg bid for 12 weeks . Change of QOL was compared both quantitatively and qualitatively between captopril and placebo groups . Change of blood pressure and side effects were also compared . RESULTS With intention-to-treat analysis , significantly more improved QOL patients could be found qualitatively in patients with captopril treatment ( 45.3 % vs 23.7 % , P = 0.0002 for physical health domain ; 48.9 % vs 26.6 % , P = 0.0002 for mental health domain ; 33.8 % vs 11.5 % , P = 0.0001 for general function domain ) . Quantitatively , the change of score of mental health , general function and total QOL of captopril ( 3.18 + /- 5.90 ; 1.65 + /- 4.43 ; 7.84 + /- 11.03 ) were significantly higher than those of placebo ( 1.32 + /- 5.13 , P = 0.00004 ; 0.64 + /- 3.45 , P = 0.0008 ; 4.19 + /- 10.33 , P = 0.0025 respectively ) , and the change of score of physical health domain ( 3.01 + /- 5.26 vs 2.23 + /- 4.79 , P = 0.044 ) was of borderline statistical significant difference . Blood pressure was significantly lowered by captopril than by placebo ( P = 0.000 ) . CONCLUSION Compared with the placebo , captopril is not only effective in lowering blood pressure , as has been established , but also effective in improving QOL in mild hypertensives", "The antihypertensive efficacy of 2.5 and 5 mg cilazapril and placebo in lowering 24-h ambulatory blood pressure ( ABP ) and BP load were compared in 42 patients with mild to moderate hypertension . After a 2-week placebo run-in period , patients were r and omized double-blind to receive either 2.5 mg cilazapril ( n = 14 ) , 5 mg cilazapril ( n = 14 ) , or placebo ( n = 14 ) for 4 weeks . There were no significant differences in 24-h and awake ABP or in office BP between 2.5 and 5 mg cilazapril . Moreover , the percentage of patients that had BP control ( mean daytime ABP less than 90 mm Hg ) was 14 % in the placebo group , 64 % and 71 % with 2.5 and 5 mg cilazapril , respectively . Furthermore , the percentage of BP load was similar with both regimens ( 29 v 36 % ) . These observations indicate that 2.5 and 5 mg cilazapril have equipotent antihypertensive efficacy", "Objective : To compare the efficacy , safety and tolerability of valsartan to an angiotensin-converting enzyme ( ACE ) inhibitor , lisinopril , and placebo in patients with mild-to-moderate essential hypertension . Design : A total of 734 men and women were r and omised in this multicentre , double-blind , optional titration , parallel group trial . Volunteers received valsartan 80 mg ( n = 364 ) , lisinopril 10 mg ( n = 187 ) or placebo ( n = 183 ) daily for 4 weeks , with subsequent titration of dose depending on response to treatment ( valsartan 80 mg titrated to valsartan 160 mg once daily or valsartan 80 mg twice daily , lisinopril 10 mg titrated to lisonopril 20 mg once daily ) . Patients were assessed at 4 , 8 and 12 weeks . Main outcome measures : The primary variable was change from baseline in mean sitting diastolic blood pressure ( SDBP ) . Other efficacy variables included sitting systolic blood pressure ( SSBP ) and percentage of ‘ successful ’ responders ( SDBP reductions in SDBP compared to placebo at endpoint of therapy ( least mean square reduction from baseline : valsartan 80/160 mg : −5.25 mm Hg ( CI −7.17 , −3.34 , P valsartan 80/80 mg twice daily : −5.63 mm hg ( ci −7.51,−3.75 , P ) ; lisinopril 10/20 mg : −6.93 mm hg , ( ci −8.81 , −5.05 , P ( placebo n = 142 , valsartan 80/80 twice daily n = 124 , valsartan 80/160 n = 114 , lisinopril 10/20 n = 120 ) , there were no significant treatment differences between valsartan 160 mg given as a single daily dose or as 80 mg twice daily ( P = 0.658 ) . Both valsartan and lisinopril produced similarly high percentages of ‘ successful ’ responders at endpoint of therapy . A somewhat higher frequency of drug related cough was observed in lisinopril treated patients ( 8 % ) compared to valsartan ( 1.1 % ) or placebo ( 0.5 % ) . Conclusions : Valsartan 80 mg daily , with titration to 160 mg daily as required , provides similar antihypertensive efficacy to lisinopril 10 mg daily with titration to 20 mg daily . Valsartan provides a new antihypertensive agent with comparable efficacy to lisinopril and appears to be associated with a reduced incidence of cough", "Summary : Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then r and omised into a double-blind parallel group study to receive either placebo , 1.25 mg cilazapril + 0.5 mg cyclopenthiazide ( CPTZ ) , 2.5 mg cilazapril + 0.5 mg CPTZ , or 2.5 mg cilazapril alone for 1 month . After oral administration of a single dose of 2.5 mg cilazapril , the active diacid cilazaprilat appeared rapidly in the plasma ( Tmax 2.0 ± 0.2 h ) . With the radioinhibitor assay used in this study , a single elimination phase of cilazaprilat was evident , with a half-life ( t1/2 ) of 2–3 h. At steady state , the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ . The Cmax and area under the curve ( AUC ) of cilazaprilat were directly proportional to dose . Cilazapril administration in the dose range of 1.25–2.5 mg produced a dose- proportional inhibition of angiotensin-converting enzyme ( ACE ) activity that was maximum 2 h after drug administration . The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure ( BP ) . The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ . There was no evidence of a dose-related anti-hypertensive effect of cilazapril at steady state and , with the small numbers of subjects used in this study , there was no evidence of 24-h BP control with monotherapy", "Summary : The antihypertensive effect of the angiotensin-converting enzyme ( ACE ) inhibitor lisinopril administered in a single dose of 20 mg was evaluated by ambulatory blood pressure monitoring ( ABPM ) in a double-blind , placebo-controlled , cross-over study . Twenty-four patients ( 21 men and 3 women , mean age 52 ± 6 years ) with mild to moderate hypertension were included in the study and r and omly assigned to two consecutive treatments with lisinopril 20 mg and placebo , each administered for 4 weeks . On the last day of each treatment , BP was assessed by noninvasive 24-h ABPM . BP was significantly lower after lisinopril than after placebo in a 24-h period ( mean 24-h systolic BP ( SBP ) with lisinopril 120 ± 7 mm Hg and with placebo 135 ± 9 mm Hg ; mean day SBP with lisinopril 125 ± 3 mm Hg and with placebo 142 ± 5 mm Hg ; mean night SBP with lisinopril 112 ± 4 mm Hg and with placebo 124 ± 6 mm Hg ; mean 24-h diastolic BP ( DBP ) with lisinopril 76 ± 6 mm Hg , and with placebo 87 ± 8 mm Hg ; mean day DBP with lisinopril 80 ± 3 mm Hg and with placebo 93 ± 4 mm Hg ; mean night DBP with lisinopril 69 ± 2 mm Hg and with placebo 79 ± 5 mm Hg , p HR ) did not differ significantly between placebo and lisinopril treatments . Repeated- measures analysis of variance ( ANOVA ) showed a significant influence on SBP ( p 0.001 ) and DBP ( p treatment . A significant time effect was also evident both for SBP ( p 0.001 ) and DBP ( p ) . The interaction of time and treatment was not significant , suggesting that the circadian rhythm of BP was not different during the two treatments . No serious side effects were observed during this study", "The antihypertensive efficacy of ramipril was evaluated using 24-h noninvasive ambulatory sphygmomanometry in this double-blind , placebo-controlled study . One hundred subjects with mild-to-moderate essential hypertension were r and omized to ramipril , 10 mg or placebo once daily for a 4-week treatment period . Ramipril decreased systolic and diastolic blood pressures throughout the 24-h period after dosing . Blood pressures measured manually 24 h postdose also showed that ramipril significantly reduced supine and st and ing blood pressures when compared with placebo . Incidences of adverse events were similar in the two study groups . Ramipril proved to be a well-tolerated agent with a sustained 24-h antihypertensive effect in this study", "Serum lipids of 80 patients with moderately severe essential hypertension under four different antihypertensive therapies were compared to ten matched hypertensives on a placebo , after eight weeks of therapy . The results in the serum lipid parameters measured after therapy showed with enalapril a significant increase in high-density lipoprotein cholesterol ( HDL-C ) and a decrease in the total cholesterol/HDL-C ratio . With benazepril a significant decrease in the total cholesterol/HDL-C ratio was obtained . With the diuretic combination Epitens the effect on serum sodium and potassium was minimal . No significant changes were found in the lipoprotein profile following the administration of the placebo . Both angiotensin converting enzyme inhibitors ( enalapril and benazapril ) induced a significant improvement in the atherogenic ratio ; as well as the calcium antagonist ( isradipine ) , though to a less extent . The diuretic Epitens induced an insignificant deterioration of the atherogenic ratio", "Benazepril hydrochloride is a new angiotensin‐converting enzyme inhibitor . In a multicenter study , 206 patients with mild to moderate hypertension were r and omized to receive benazepril at a dose of 2 , 5 , 10 , or 20 mg , hydrochlorothiazide , 25 mg , or placebo once daily for 4 weeks . The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide : −12.217.7 mm Hg and −13.4/−7.5 mm Hg , respectively . Hydrochlorothiazide proved to be more effective in black subjects . At lower dosage levels of benazepril ( 2 , 5 , and 10 mg ) , blood pressure reduction was not significantly different from that with placebo . In those patients who failed to achieve goal diastolic blood pressure of hydrochlorothiazide ( 25 mg/day ) to benazepril , hydrochlorothiazide , or placebo produced a substantial additional decrease in blood pressure over a 2‐week period . No definite adverse effects on hématologie measurements , serum biochemistry test results , or urinalyses were noted . Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug", "Although it has been recognized that enalapril lowers blood pressure by reducing the total peripheral vascular resistance , its direct effect on blood vessels is largely unknown . Little information is available about the influence of enalapril on the different vascular regions . Ten patients with moderate essential hypertension were treated with enalapril 20 mg daily in a double-blind , placebo controlled cross-over study for six weeks during each period . Blood pressure and heart rate were measured in supine , sitting and st and ing position . Venous capacity was derived from pressure volume curves plotted simultaneously at forearm and calf . Arterial blood flow at rest and during reactive hyperemia was measured at calf and finger by plethysmography . Enalapril increases venous capacity in upper and lower limbs in patients with moderate essential hypertension . Also , there is vasodilation of calf and finger arteries both at rest and during reactive hyperemia . Finger and calf arteries contribute to the decrease of the total peripheral vascular resistance during treatment with enalapril ; thus , ACE inhibition is capable of correcting the increased peripheral resistance which often is the main cause of arterial hypertension", "The use of ambulatory blood pressure monitoring in clinical studies offers some advantages in comparison to the clinic blood pressure measurement . In fact , this approach does not induce any alerting reaction and provides 24-h blood pressure values that are more reproducible and not affected by the placebo effect . This allows a better evaluation of blood pressure under antihypertensive treatment and an optimization of the number of patients to be studied in pharmacologic trials . In a recent double-blind , parallel-group study , ambulatory blood pressure monitoring was used to investigate the antihypertensive efficacy of a new angiotensin-converting enzyme inhibitor , tr and olapril , in 62 mild and moderate hypertensive patients . After a washout period , patients received tr and olapril , 2 mg o.d . , or placebo for 6 weeks , followed by a second washout period . Clinic and 24-h blood pressures were assessed at the end of each period . In comparing the pre- and post-treatment period , tr and olapril significantly reduced clinic and 24-h systolic and diastolic blood pressures . The fall was evident throughout the 24 h and was statistically significant also in the last 4 h of blood pressure monitoring . The placebo group did not show any significant blood pressure change . Thus , tr and olapril , 2 mg once daily , is effective in reducing blood pressure . Its efficacy over 24 h is better documented by 24-h blood pressure monitoring than by isolated clinic blood pressure measurement", "Objective To compare the effects of a calcium antagonist ( nitrendipine ) and an angiotensin converting enzyme inhibitor ( enalapril ) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension . Design A double-blind r and omized , placebo-controlled trial . Setting General practitioners referred patients to the trial physician . Patients The study population comprised 121 patients with non-insulin-dependent diabetes mellitus . Inclusion criteria for blood pressure were diastolic blood pressure 90–115 mmHg and systolic blood pressure ⩽ 200 mmHg , while subjects were not being administered blood-pressure-lowering drugs for 3 weeks . Intervention Patients were r and omly allocated to receive nitrendipine ( n = 40 ) , enalapril ( n = 40 ) or placebo ( n = 41 ) . The treatment period was 48 weeks . Main outcome measures The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment . The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly . Left ventricular mass was measured by M-mode echocardiography . Results Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures . During 48 weeks left ventricular mass index decreased by 5 % for patients in the nitrendipine group ( decrease by 12 g/m2 , 95 % confidence interval 1–23 ) , remained about the same for patients in the enalapril group ( decrease by 1 g/m2 , 95 % confidence interval decrease by 10 to increase by 9 ) and increased by 9 % for patients in the placebo group ( increase by 9 g/m2 , 95 % confidence interval 2–16 ) . Conclusion These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index . Enalapril appears not to induce regression , but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo . J Hypertens 16:689–696 © 1998 Lippincott-Raven Publishers", "We have previously shown that enalapril , when given acutely to renovascular patients , exerted a dose-dependent hypotensive effect . To address the same problem in chronically treated essential hypertensives , we studied 116 uncomplicated essential hypertensives , whose diastolic blood pressure was greater than or equal to 95 mm Hg at the end of a two-week placebo run-in period ( time 0 ) . According to a r and omized crossover design , these patients received three doses ( 10 , 20 , or 40 mg ) of enalapril qd and a placebo , each treatment being given for one month . At the end of each treatment period as well as at time 0 , blood pressure and heart rate were measured 24 hours after the last dosing . In spite of a two-week run-in placebo period , placebo treatment further and significantly reduced blood pressure ; however enalapril further and significantly reduced blood pressure when compared to placebo . Although absolute blood pressure values after 40 mg of enalapril were significantly lower than those after 10 mg of enalapril the relevance of this difference , mainly when compared to placebo , seems to be inconsistent . Taken together these data suggest that the hypotensive effect of enalapril chronically given to essential hypertensives and measured 24 hours after last dosing , is dose independent", "In a r and omized , double-blind trial , 2 doses of ramipril ( 2.5 and 5 mg once daily ) were compared with placebo in patients with mild to moderate essential hypertension . A 2-week placebo run-in phase was followed by 4 weeks of treatment . Eighty-six patients entered the study and 17 withdrew during the course of the study . Both doses of ramipril appeared to be more effective than placebo in reducing blood pressure , but significant differences between 2.5 mg of ramipril and placebo were not found in any statistical analyses . In the endpoint analyses ( taking the last measurement from each patient ) , the patients receiving 5 mg of ramipril had significantly larger decreases in blood pressure than the patients receiving placebo ( t tests : st and ing systolic , p less than 0.001 ; supine diastolic , p less than 0.05 ; st and ing diastolic , p less than 0.05 ) and also than the patients receiving 2.5 mg of ramipril ( st and ing systolic , p less than 0.05 ) . It appears from the results of this study that the minimum effective dosage of ramipril is 5 mg once daily . No clinical ly relevant side effects or clinical ly relevant changes in laboratory values were observed", "The effects of the ACE inhibitor spirapril and of hydrochlorothiazide on left ventricular diastolic function were studied . Thirteen patients with mild to moderate essential hypertension completed this r and omized , double-blinded , placebo-controlled , crossover study . After a three-week run-in period the patients entered three periods lasting four weeks each , wherein they were treated with placebo , spirapril , or hydrochlorothiazide . Blood pressure , hemodynamic variables ( stroke volume , heart rate , cardiac output , index of contractility , and systemic vascular resistance ) , echocardiography ( left ventricular mass ) , and Doppler-derived atrial to early (A/E)-ratio velocity time integrals ( VTI ) were measured at the end of each of the four periods . Spirapril lowered the A/E-ratio VTIs ( 0.57 , 0.12 - 1.00 ) ( P A/E-ratio VTI in those patients with elevated values . The hemodynamic variables , left ventricular mass , and end-systolic wall stress were unchanged during all three treatments . There were no significant changes in mean blood pressure during the treatment periods . These results indicate that spirapril lowers A/E ratio within four weeks in patients with mild to moderate essential hypertension . It thereby seems able to improve left ventricular diastolic function . The effect is not dependent upon changes in hemodynamic variables , blood pressure , left ventricular mass , or end-systolic wall stress", "BACKGROUND The excess morning risk of myocardial infa rct ion and stroke may be attributable to the rapid rise in blood pressure ( BP ) and heart rate in the hours after awakening . The aim of this r and omized , double-blinded , placebo-controlled , multicenter study was to compare once-daily , controlled-onset , extended-release ( COER-24 ) verapamil to enalapril and losartan on BP and heart rate during the postawakening morning phase as well as throughout the 24-h period . METHODS A total of 406 patients were r and omized to an 8-week forced-titration period with one of the following : 1 ) COER-24 verapamil 240 mg/day titrated to 360 mg/day ; 2 ) enalapril 10 mg/day titrated to 20 mg/day , 3 ) losartan 50 mg/day titrated to 100 mg/day , or 4 ) placebo . Office BP and heart rate and ambulatory 24-h BP monitoring was performed at baseline , 4 weeks , and 8 weeks . RESULTS Each active treatment , as compared with placebo , lowered BP both during the morning hours as well as the entire 24-h period . COER-24 verapamil was more effective in lowering morning systolic ( -16.6 mm Hg ) and diastolic ( -11.9 mm Hg ) BP than either enalapril or losartan ( P COER-24 verapamil ( -11.6/-8.4 mm Hg ) were comparable to enalapril ( - 13.4/-8.3 mm Hg ; P = NS ) . Losartan achieved a similar 24-h effect on systolic pressure ( -9.3 mm Hg ) but was less effective on diastolic pressure ( -5.4 mm Hg ; P = .004 v COER-verapamil ) . Unlike losartan or enalapril , COER-24 verapamil was the only treatment to lower the heart rate over both the 24-h period ( -4.6 beats/min ; P hours ( -4.6 beats/min ; P rate of rise in BP , heart rate , and rate-pressure product occurred during the postawakening period with COER-verapamil ( P = .03 ) but not with either of the other treatment arms . Lastly , the decline in BP at night was similar for COER-verapamil and losartan and greater with enalapril ( P = .014 ) CONCLUSIONS COER-24 verapamil produces changes in BP and pulse that more closely match the normal circadian hemodynamic rhythms than either do enalapril or losartan", "OBJECTIVE To assess the efficacy and safety of several combinations of benazepril , an angiotensin-converting enzyme inhibitor , and hydrochlorothiazide , as compared with placebo , in the treatment of patients with essential hypertension . DESIGN A 6-week , r and omized , double-blind , parallel study conducted at 24 centers . A placebo run-in period of 1 to 4 weeks preceded the double-blind phase . PARTICIPANTS AND SETTING Male and female out patients , aged 18 years and older , were eligible to participate if their sitting diastolic blood pressure was between 95 and 114 mm Hg at the last two consecutive visits during the placebo phase . Among the 334 patients who entered the double-blind phase , 17 % were aged 65 years or older and 26 % were black . Eleven patients withdrew because of adverse experiences , including two patients receiving placebo . INTERVENTIONS Patients received placebo ; benazepril , 20 mg ; hydrochlorothiazide , 25 mg ; or combination therapy with benazepril/hydrochlorothiazide , 5/6.25 mg , 10/12.5 mg , 20/25 mg , 20/6.25 mg , or 5/25 mg , once daily for 6 weeks . MAIN OUTCOME MEASURES The mean change from baseline in sitting diastolic blood pressure at end point ( last postr and omization measurement carried forward ) in the double-blind phase . Combination therapy with benazepril/hydrochlorothiazide , 20/25 mg , was compared with benazepril , 20 mg alone , and hydrochlorothiazide , 25 mg alone . Sitting systolic blood pressure and the effect of race and age on treatment efficacy were also evaluated . RESULTS Compared with placebo , all benazepril/hydrochlorothiazide combinations produced statistically significant reductions from baseline in sitting diastolic and systolic blood pressures at study end point . In the benazepril/hydrochlorothiazide , 20/25 mg , group , the adjusted mean changes in sitting diastolic blood pressure at end point were statistically significantly greater than those in the monotherapy treatment groups ( benazepril , 20 mg , P hydrochlorothiazide , 25 mg , P tolerated . Decreases in mean serum potassium level with hydrochlorothiazide monotherapy were reduced or eliminated with combination therapy . CONCLUSION Benazepril in combination with hydrochlorothiazide , including a low-dose combination of 5/6.25 mg , is effective in reducing sitting diastolic and systolic blood pressure in patients with hypertension", "A multicenter , double-blind , r and omized , and placebo-controlled trial , the Perindopril Therapeutic Safety Study ( PUTS ) , was design ed to assess the interaction between angiotensin-converting enzyme ( ACE ) inhibition and the diseases and therapies commonly found associated with mild hypertension . A total of 480 male and female patients aged 30 - 70 years with a diastolic pressure of 90 - 104 mm Hg were included after a 3-week placebo run-in if they satisfied st and ard criteria for any of the following : hyperlipidemia , type II diabetes , ischemic heart disease , cardiac arrhythmia , peripheral arterial occlusive disease , nephropathy with proteinuria , chronic obstructive lung disease or treatment with nonsteroidal anti-inflammatory drugs ( NSAIDs ) . At the end of the placebo run-in period , patients were r and omly assigned to either placebo or perindopril 4 mg once daily . A total of 460 patients completed the 6-week double-blind phase , comprising 3 assessment s at 1 , 3 , and 6 weeks . In this report , the principal results obtained in 5 disease groups ( hyperlipidemia , type II diabetes , ischemic heart disease , nephropathy with proteinuria , and NSAID treatment ) will be reported . A total of 269 patients belonging to one of the aforementioned 5 disease groups completed the double-blind phase of the study and were included for statistical evaluation . In the perindopril group , systolic and diastolic blood pressures decreased significantly more than in the placebo group , and a sitting diastolic blood pressure of 90 mm Hg was achieved in 65 % of patients in the perindopril group and 30 % of patients in the placebo group . The incidence of symptoms spontaneously reported by the patients was low : 2 patients of the perindopril group complained of cough . ( ABSTRACT TRUNCATED AT 250 WORDS", "Objective To evaluate the efficacy and duration of action of the angiotensin converting enzyme inhibitor quinapril hydrochloride by using ambulatory blood pressure monitoring . Design Eleven centers in the USA and Canada entered 155 patients with previously diagnosed hypertension into a 4-week placebo-baseline phase . Twenty patients ( 13 % ) with elevated diastolic blood pressure ( DBP ) only by cuff measurement were excluded from entry into a double-blind test based on ambulatory blood pressure monitoring , and 135 patients with a mean waking blood pressure of 155/100 mmHg were assigned r and omly to receive either quinapril or placebo once a day for 8 weeks , with optional titration to a higher dose after 4 weeks , based on the DBP response assessed by repeat ambulatory blood pressure monitoring only . Results Quinapril therapy produced highly significant decrease in mean daytime DBP compared with placebo . The antihypertensive effect of quinapril was evident over 24 h , with 50 % of the peak effect remaining at the trough . After 4 weeks of treatment 49 % of the patients in the quinapril group were titrated to the higher dose compared with 86 % of the patients who had been receiving placebo . More than 70 % of the patients in the quinapril group who remained at the low dose would have been titrated to the higher dose based solely on the clinic DBP measurements . Conclusions The use of ambulatory blood pressure monitoring in the present study reduced the false-positive response to placebo and lessened the likelihood of titrating patients to the higher dose of quinapril in comparison with the number that would have been so treated based on clinic blood pressure measurements alone . More importantly , our results suggest that the convenience , ease and relatively low cost of traditional cuff blood pressure measurement should be weighed against the potential shortcomings of the method", "OBJECTIVE : To compare the effects on office blood pressure and home blood pressure of placebo and active drug administration . DESIGN : After a 2-week wash-out period , patients with mild-to-moderate hypertension entered a 2-week single-blind placebo period and then a 4-week double-blind period . Patients were r and omly assigned to be administered either 2 mg tr and olapril once daily or its placebo in a 2:1 proportion . Office blood pressure was measured by a physician at the end of each period , using a mercury sphygmomanometer ( mean of three consecutive measurements ) . Home blood pressure was measured during the last week of each period according to st and ard procedure carefully taught to each patient by the physician . Compliance was checked by using electronic pill boxes . RESULTS : Data for 34 of the 44 patients who entered the study were eligible for analysis . Baseline systolic blood pressure/diastolic blood pressure were significantly ( P = 0.0001/P = 0.0001 ) higher for office blood pressure ( 161/101 mmHg ) than they were for home blood pressure ( 145/93 mmHg ) . There was no statistically significant difference between the placebo and active-treatment groups at baseline . During the single-blind period , blood pressures measured at the office and at home did not change significantly . Office blood pressure decreased by 2.7 + /- 10 mmHg for systolic blood pressure and by 0.5 + /- 4 mmHg for diastolic blood pressure whereas home blood pressure increased by 0.8 + /- 6 mmHg for systolic blood pressure and by 0.7 + /- 4 mmHg for diastolic blood pressure . During the double-blind period , office blood pressure fell significantly with tr and olapril treatment ( systolic by 10.2 + /- 12 mmHg , diastolic by 8.3 + /- 6 mmHg ; P = 0.0005/0.0001 , versus single-blind placebo period ) but this decrease was not significantly different ( P = 0.45/0.92 ) from the fall in members of the placebo group ( systolic by 6.9 + /- 9 mmHg , diastolic by 8.0 + /-6 mmHg ; P = 0.04/0.002 , versus single-blind placebo period ) . Thus , no antihypertensive effect of tr and olapril was demonstrated . The fall lin home blood pressure with tr and olapril treatment was significant ( systolic by 10.7 + /- 8 mmHg , diastolic by 5.8 + /- 5 mmHg ; both P = 0.0001 , versus single-blind placebo period ) and was significantly greater ( P = 0.0004/0.004 ) than the minimal change observed with placebo ( systolic fell by 0.2 + /- 5mmHg , diastolic fell by 0.6 + /- 4 mmHg ; P = 0.90/0.62 , respectively , versus single-blind placebo period ) . The evening decrease in home blood pressure was similar to the morning decrease in home blood pressure in members of the tr and olapril-treated group . The result ing morning : evening decrease in blood pressure ratio was 0.83 for diastolic blood pressure and 0.95 for systolic blood pressure . For the subgroup of responders , mean of individual ratios was 0.77 + /- 0.43 for diastolic blood pressure and 0.70 + /- 0.39 for systolic blood pressure . CONCLUSION : The placebo effect observed with office blood pressure measurements does not occur with home blood pressure measurements . Expected treatment effect can alter a physician 's blood pressure readings . The precision of measurements is greater with home blood pressure ( there is a lower SD ) . Use of home blood pressure measurements increases the power of comparative trials , allowing one either to study fewer subjects or to detect a smaller difference in blood pressure", "Objective To compare the effect of captopril with that of placebo on peripheral and hepatic insulin action in essential hypertension , in light of evidence that insulin resistance is associated with cardiovascular risk . Design R and omized , double-blind , placebo-controlled , crossover trial , with 8 week treatment periods of captopril and placebo preceded and separated by 6 weeks of placebo . Setting Belfast teaching hospital . Patients Eighteen Caucasian nondiabetic patients ( 10 males ) , aged under 65 years , with essential hypertension , recruited from general practice s in the greater Belfast area . Interventions Captopril at 50 mg twice a day or placebo twice a day for two 8 week treatment periods . Main outcome measures Peripheral and hepatic insulin sensitivity assessed by glucose clamps . Results Fourteen patients completed the study . Mean ( ± SEM ) levels of fasting glucose , fasting insulin and postabsorptive hepatic glucose production were similar after captopril and placebo ( 5.4 ± 0.1 versus 5.4 ± 0.1 mmol/l , 10.6 ± 2.2 versus 9.5 ± 1.1 mU/l , 11.2 ± 0.6 versus 11.0 ± 0.5 mmol/kg per min , respectively ) . During hyperinsulinaemia , hepatic glucose production was suppressed to comparable levels after both treatments ( 4.8 ± 0.6 versus 4.3 ± 0.6 mmol/kg per min ) and exogenous glucose infusion rates required to maintain euglycaemia were also similar ( 30.0 ± 2.6 versus 30.3 ± 2.6 mmol/kg per min ) . Conclusion Captopril therapy in uncomplicated essential hypertension has no effect on peripheral or hepatic insulin sensitivity", "A multicenter , double-blind , placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem , in a sustained release preparation , and the angiotensin converting enzyme inhibitor , lisinopril , in the treatment of elderly Chinese patients with mild-to-moderate hypertension . In addition to the hypotensive effects of combinations of both drugs compared with monotherapy , all given once daily , the effect on quality of life was also evaluated . This study consisted of a 3 x 2 multifactorial design in which 156 women and men with a sitting diastolic pressure of between 95 mm Hg and 114 mm Hg , after a 4-week placebo washout phase , were r and omized to one of six treatment groups for 12 weeks of active treatment . Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of systolic and diastolic blood pressure . Compared with placebo , lisinopril 10 mg had an effect intermediate between the diltiazem doses . The combinations of diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg showed increased efficacy in reducing systolic and diastolic blood pressure compared to these drug doses used in monotherapy , but the effect of the combinations was less than predicted by an additive model . Although the total number of other adverse events reported was similar for all active treatment groups compared to placebo , lisinopril-induced cough was common with an incidence of 31 % after rechallenge . Premature drug withdrawal was necessary in four of 78 patients receiving lisinopril , due to intractable cough . The combination of diltiazem 240 mg and lisinopril 10 mg was significantly more effective at reducing blood pressure than either drug alone ; this additive effect did not result in a higher rate of adverse effects or impairment of quality of life . Thus , combination therapy with these agents was well tolerated and result ed in increased efficacy in these elderly patients", "This r and omized , double-blind , double-dummy , placebo-controlled , parallel-group study evaluated the dose-response relationship of telmisartan in 207 patients with mild to moderate hypertension ( diastolic blood pressure [ DBP ] 100 to 114 mmHg ) . After a 28-day placebo run-in period , patients were r and omized to 28 days of once-daily , double-blind , double-dummy treatment with telmisartan 40 , 80 , or 120 mg ; enalapril 20 mg ; or placebo . Blood pressure ( BP ) was manually recorded for 12 hours after the first dose and after 24 hours at baseline ( Day 0 ) , Day 1 , and Day 28 of double-blind treatment . Pharmacokinetic and pharmacodynamic parameters were assessed from telmisartan plasma concentrations . All doses of telmisartan and enalapril significantly reduced BP compared with placebo ( p + /- SE reductions in supine DBP after 28 days of treatment ranged between 7.9 + /- 1.3 mmHg and 9.8 + /- 1.3 mmHg in the telmisartan groups , 9.6 + /- 1.3 mmHg with enalapril , and 1.5 + /- 1.3 mmHg with placebo . Mean + /- SE reductions in supine systolic blood pressure ( SBP ) were between 10.0 + /- 2.2 mmHg and 15.5 + /- 2.2 mmHg with telmisartan versus 10.2 + /- 2.1 mmHg with enalapril ; placebo increased supine SBP by 3.5 + /- 2.1 mmHg . The BP reductions after 4 weeks of treatment with telmisartan were no different from those achieved with enalapril . No significant linear trend in BP reduction was evident among telmisartan doses . Reductions in SBP and DBP were maintained over the 24-hour period at Day 28 . Treatment did not affect supine heart rate . Trough/peak DBP ratios were > or = 85 % for all telmisartan doses versus 65 % for enalapril . High interpatient variability in telmisartan plasma concentrations was observed . For example , mean + /- SD values for Cmax were 159 + /- 104 ng/mL for telmisartan 40 mg , 693 + /- 606 ng/mL for telmisartan 80 mg , and 1635 + /- 1406 ng/mL for telmisartan 120 mg . Plasma concentration-effect analyses indicated that the antihypertensive effects of telmisartan 40 , 80 , and 120 mg are at the plateau region of the concentration-response curve . All active treatments were well tolerated , with tolerability profiles similar to placebo , and telmisartan did not produce any clinical ly relevant first-dose effects . These data confirm the antihypertensive efficacy and placebo-like tolerability of telmisartan ", "The efficacy and safety of various doses of losartan potassium , a specific and selective angiotensin II receptor antagonist , were compared with those of placebo and enalapril maleate 20 mg in patients with mild to moderate essential hypertension in a r and omized , double-blind , parallel study . We r and omly allocated 576 patients at the end of a 4-week placebo baseline period to 8 weeks of once-daily double-blind treatment with losartan potassium 10 , 25 , 50 , 100 , or 150 mg , enalapril maleate 20 mg , or placebo . After 8 weeks of treatment , mean reductions from baseline in supine systolic/diastolic pressure 24 hours after dosing ( trough ) for losartan potassium 10 , 25 , 50 , 100 , and 150 mg , enalapril maleate 20 mg , and placebo were 7.6/7.9 , 7.8/6.8 , 13.0/10.1 , 8.9/9.9 , 10.5/9.7 , 14.7/11.2 , and 3.8/5.6 mm Hg , respectively . Compared with mean changes in supine diastolic pressure in the placebo group , losartan potassium 50 to 150 mg and enalapril maleate 20 mg produced clinical ly important and statistically significant reductions ( P blood pressure . At 24 hours after dosing , the blood pressure changes obtained with losartan potassium 50 mg were essentially identical to those obtained with enalapril maleate 20 mg . While there was a dose-related effect with losartan potassium from 10 to 50 mg at peak ( 6 hours after dosing ) , doses of 10 and 25 mg were not consistently different from placebo 24 hours after dosing . To assess the once-daily effect of losartan potassium , trough-to-peak ratios of the mean changes in supine diastolic pressure after 8 weeks of treatment were calculated . ( ABSTRACT TRUNCATED AT 250 WORDS", "The dose-response relationship of ramipril was examined in 216 subjects with mild-to-moderate essential hypertension in a double-blind , placebo-controlled , multicenter study . Ramipril capsules ( 1.25 , 2.5 , 5 , or 10 mg ) or placebo capsules were administered once daily for 12 weeks . Significant reductions in supine and st and ing diastolic and systolic blood pressures were seen at end point in the ramipril 2.5 , 5 , and 10 mg treatment groups compared with placebo . The antihypertensive effect was greater at higher doses . The minimum effective dose of ramipril was 2.5 mg once daily", " Quinapril HCl is a novel , nonsulf hydryl angiotensin-converting en zyme ( ACE ) inhibitor . The Study Group evaluated its efficacy ( 20 , 40 , 80 mg daily with forced dose titration determination at trough blood pres sure ) once daily versus twice daily versus placebo , as well as its tolera bility and safety , in 270 patients with mild to moderate essential hyperten sion ( WHO Stages I and II , sitting diastolic blood pressure [ DPB ] ≥95 mm Hg ) , for twelve weeks . Reduc tions in DBP of up to 13 mm Hg were obtained , and in full dosage more than 65 % of patients achieved a re duction in DBP of 10 mm Hg or more from baseline or reduced their DBP to 90 mm Hg or less . Quinapril was well tolerated , and reported adverse effects were scarcely more frequent than in the placebo group . Once daily doses of quinapril were as safe and effective as twice-daily doses . Quina pril is likely to exhibit good therapeu tic utility in the management of essential hypertension", "PURPOSE Many hypertensive patients have other , usually long-term diseases . Antihypertensive therapy may interfere with these diseases and their therapies . In the present study , the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated . PATIENTS AND METHODS In a multicenter , double-blind , r and omized , placebo-controlled trial , the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases : hyperlipidemia , type II diabetes mellitus , ischemic heart disease , cardiac arrhythmia , peripheral arterial occlusive disease , nephropathy with proteinuria , chronic obstructive pulmonary disease , or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs ( NSAIDs ) . After a 3-week single-blind placebo run-in , the patients received either perindopril ( 4 mg/d ) or matching placebo for 6 weeks . RESULTS Blood pressure was effectively reduced by perindopril irrespective of the associated disease . The rate of spontaneously reported side effects was low . Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies . Moreover , favorable actions could be observed in patients with ischemic heart disease ( reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks ) , in patients with proteinuria ( decrease in albuminuria in patients with normal serum creatinine levels ) , and in patients with NSAID-treatment ( increase in prostagl and in E2 concentration in gastric mucosa suggesting gastric cytoprotection ) . CONCLUSION This trial shows that ACE-inhibition with perindopril represents a simple , safe , and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies", "Hypertension is an important cardiovascular risk factor and the goal of its pharmacologic treatment is to reduce morbidity and mortality . Treatment is usually initiated with a low dose of a single agent and titrated to a higher dose as required . As many as 50 % of patients require the addition of a second agent to achieve satisfactory blood pressure control . The aim of this study was to assess the dose-response relationship of nitrendipine and enalapril alone or in fixed combination in the treatment of mild to moderate hypertension . A total of 496 patients were enrolled in a multicenter , r and omized , double-blind , factorial- design , parallel-group clinical trial comparing placebo , nitrendipine ( 5 , 10 , and 20 mg ) and enalapril ( 5 , 10 , and 20 mg ) alone or in combination . After a single-blind , 2-week placebo run-in period , 414 patients whose diastolic blood pressure ranged between 90–109 mm Hg were r and omly assigned to a treatment group . The combination of nitrendipine and enalapril , particularly regimens including nitrendipine 20 mg and enalapril 5 or 10 mg , were significantly superior to both monotherapies ; mean diastolic blood pressure reductions from baseline to last visit were −12.5 and −14.3 mm Hg , respectively . Response surface analysis provided further evidence that these combinations were optimal in terms of anti-hypertensive efficacy . All treatments were well tolerated and the incidence of adverse events did not differ significantly between groups . In summary , the anti-hypertensive efficacy of the combination was found to be superior to both monotherapies at any doses . The dose combination achieving the greatest blood pressure reduction was nitrendipine 20 mg and enalapril 10 mg", "This multicenter , double-masked , r and omized , parallel-group study compared the efficacy , tolerability , and safety of amlodipine 5 mg/benazepril 20 mg , amlodipine 5 mg , benazepril 20 mg , and placebo in patients with essential hypertension . After a placebo run-in period , 308 patients ( all white ) were r and omized to treatment groups and took medication once daily for 8 weeks . Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing . Patients wore a noninvasive blood pressure monitor for 24 hours before r and omization and before the final visit . Investigators recorded adverse experiences at r and omization and at study weeks 4 and 8 , and obtained specimens for laboratory testing at r and omization and at study week 8 . Three hundred seven patients were evaluated for efficacy , and 308 for tolerability and safety . At end point ( the last postr and omization measurement for each patient ) , the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy . The results of 24-hour monitoring showed that the amlodipine/benazepril treatment , unlike monotherapy , maintained the hourly mean diastolic blood pressure at responder rate of 87.0 % was observed with amlodipine 5 mg/benazepril 20 mg versus 67.5 % , 53.3 % , and 15.8 % with amlodipine , benazepril , and placebo , respectively . This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant . Drug-related adverse events occurred in 15.6 % of patients in the amlodipine/benazepril group and in 24.7 % , 6.5 % , and 11.7 % of patients in the amlodipine , benazepril , and placebo groups , respectively . Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group . Overall , once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinical ly superior to amlodipine 5 mg alone , benazepril 20 mg alone , and placebo , was well tolerated , and was associated with less edema than the amlodipine treatment", "The new angiotensin converting enzyme inhibitor , enalapril ( MK-421 ) , was tested by a double-blind trial . Patients with uncomplicated essential hypertension were r and omly allocated to one of two stepped-care treatment groups : enalapril 20 mg once-a-day , or placebo as the first step , followed when necessary by the successive addition of hydrochlorothiazide ( 25 and 50 mg ) , oxprenolol ( 160 and 320 mg ) and dihydralazine ( 50 and 100 mg ) . Blood pressure was normalized in both groups , although the enalapril group showed lower systolic and diastolic blood pressures than the placebo group ( systolic 130.5 + /- 12 versus 136.6 + /- 9 mmHg , P less than 0.01 ; diastolic 82.8 + /- 6 versus 87.0 + /- 5 mmHg , P less than 0.001 ) . These results were obtained with a smaller number of tablets per day ( 2.6 + /- 1.8 versus 4.2 + /- 2.4 mmHg , P less than 0.0001 ) . Plasma potassium was identical for both groups at the start of treatment . At the end of the study , it was significantly higher in the enalapril group than in the placebo group ( 4.1 + /- 0.3 versus 3.9 + /- 0.5 mmol/l ; P less than 0.05 ) . Spontaneous complaints were noted during the bi-weekly or monthly visit and were also expressed by patients completing a self-administered question naire . Differences in spontaneous complaints or in the symptoms evaluated by the question naire were not significant . The increase in the number of symptoms at the end of the study was greater in the placebo group than in the enalapril group , but the difference was not statistically significant . ( ABSTRACT TRUNCATED AT 250 WORDS", "The dose-response relationship of enalapril was evaluated in a double-blind , balanced , two-period , incomplete-block study in 91 patients with mild to moderate essential hypertension . Patients were r and omly assigned to two of six treatments : placebo , 2.5 , 5 , 10 , 20 and 40 mg/day of enalapril maleate . There were two 3-week treatment periods , each preceded by a 4-week , single-blind placebo washout . Each dose of enalapril produced significant decreases in st and ing and supine systolic and diastolic blood pressure after 2 and 3 weeks of treatment . There were no significant changes on placebo . There was a significant linear dose response relationship for both mean blood pressure and mean change from baseline in blood pressure ( P less than 0.01 for systolic and mean arterial pressure , and P less than 0.05 for diastolic pressure ) . Enalapril was associated with an increasing dose-response relationship across the 2.5 - 40 mg/day range . The 2.5 mg/dose is effective in some patients ; however , doses greater than or equal to 10 mg/day may be necessary to achieve satisfactory blood pressure control", "Summary : The effect of the angiotensin-converting enzyme (ACE)-inhibitor perindopril on serum lipids and apolipoprotein concentrations were assessed in a multicenter , r and omized , double-blind , placebo-controlled study in 51 hyperlipidemic patients treated for mild hypertension . Perindopril was given as a single morning dose ( 4 mg ) for 6 weeks . During the treatment period , blood pressure ( BP ) was significantly ( p placebo treatment . Neither total cholesterol and triglycerides nor high-density-lipoprotein and apolipoprotein AI and B levels were significantly altered by drug treatment as compared with placebo . Although perindopril had good antihypertensive effect in patients with mild hypertension and hyperlipidemia , it had no adverse effects on lipid metabolism in these patients . Therefore , perindopril is recommended for antihypertensive treatment , especially in hypertensive patients with concomitant hyperlipidemia", "Short-term results of this double-blind control trial ( previously reported ) in patients with initial diastolic blood pressures ( DBP ) in the range of 92 - 109 mm Hg indicated that doses of 12.5 or 25 mg captopril ( C ) three times daily ( t.i.d . ) and 37.5 mg twice daily ( b.i.d . ) had similar antihypertensive effectiveness as 50 mg t.i.d . After 7 weeks of C , the addition of hydrochlorothiazide ( H ) to two-thirds of the patients enhanced the antihypertensive response . This report presents the results of unchanged and uninterrupted treatment for 9.5 months in 46 patients taking C alone , and for 7.8 months in 94 patients taking C plus H or H alone . With C alone , reductions in DBP averaged 8.3 , 11.0 , 15.1 , and 17.5 mm Hg with the 12.5 , 25 , 37.5 , and 50 mg doses respectively . The response to the 12.5 mg dose only was significantly less than the 50 mg dose . With H alone , the reduction in DBP averaged 10.6 mm Hg and with C plus H reductions averaged 15.6 , 18.1 , 16.8 , and 18.7 mm Hg with the 12.5 , 25 , 37.5 , and 50 mg doses of C , respectively . Reductions in DBP with C plus H regimens were significantly different from H alone . There was no waning of effectiveness from short to long term except for the 12.5 mg dose of C alone . During the long-term phase , two patients developed rash and one lost the sense of taste . Neutropenia in one patient probably was not drug-related . There were no terminations for elevated DBP greater than 104 mm Hg on two successive visits . ( ABSTRACT TRUNCATED AT 250 WORDS", "To test the dose responses of piretanide , ramipril , and their combination in patients with essential hypertension , a prospect i ve , r and omized , double-blind , placebo-controlled trial was conducted in 480 patients . Twelve separate groups were studied : placebo , piretanide 3 mg , piretanide 6 mg , ramipril 2.5 mg , ramipril 5 mg , ramipril 10 mg , and their combinations , as single daily morning doses . Patients were r and omized after a 2-week run-in period without drugs ; treatment was given for 6 weeks . A dose response compared with placebo was found for both drugs ; the combination was more effective than either drug alone . Piretanide 6 mg , combined with ramipril 5 mg , provided optimal blood pressure reduction . Self-reported adverse effects of both drugs and their combinations did not exceed those reported for placebo . A surface analysis suggested that piretanide primarily reduced systolic blood pressure , whereas ramipril was more effective in reducing diastolic blood pressure . The data attest to a combined efficacy of piretanide and ramipril in decreasing arterial blood pressure", "OBJECTIVE To evaluate the antihypertensive effects of cilazapril , a new angiotensin-converting enzyme inhibitor , on clinic and ambulatory blood pressure ( ABP ) after first and last dose administrations . DESIGN Four weeks r and omized , double-blind , controlled trial of three regimens . SETTING Six hypertensive research clinics in Canada . PATIENTS After a two-week placebo run-in period , 130 patients aged 22 to 77 years with mild to moderate essential hypertension were r and omized and evaluated . Exclusion criteria were secondary hypertension , childbearing potential and other significant diseases . INTERVENTION Patients were assigned to cilazapril 2.5 mg ( 44 patients ) , cilazapril 5 mg ( 42 ) or placebo ( 44 ) . Fourteen patients in each group were further evaluated in a sub study by 24 h ABP monitoring . MAIN RESULTS Cilazapril in either dosage induced significant and similar antihypertensive effects on clinic blood pressure shortly after dosing ( 2 to 4 h ) , persisting during chronic treatment ; however , no relevant effect persisted at the end of dosing ( 24 h ) . After four weeks , at the end of dosing , 22 , 24 and 38 % of patients were clinical responders ( decrease in sitting diastolic blood pressure 10 mmHg or greater ) on placebo , 2.5 or 5 mg ( differences not significant ) . Conversely , both cilazapril regimens induced similar and significant ( P mean 24 h ABP compared with placebo . Moreover , 7 , 50 and 48 % of patients exhibited a reduction in mean 24 h diastolic blood pressure 10 mmHg or greater on placebo , cilazapril 2.5 or 5 mg , respectively . Furthermore , both regimens induced adequate trough : peak ratios on ABP", "1 . This was a multicentre , double-blind , parallel study in 216 patients with mild to moderate ( supine diastolic blood pressure = 95 - 115 mm Hg ) essential hypertension . 2 . After a 4-week placebo washout , patients were r and omized to placebo or lisinopril 1.25 , 5.20 or 80 mg once daily for 6 consecutive weeks . Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2 , 0 , 2 , 4 , and 6 . 3 . There was a linear dose-response relationship for both supine and erect blood pressure . Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups . 4 . Lisinopril , at doses up to 80 mg day-1 , was well tolerated", "The antihypertensive efficacy of N‐[(S)‐I‐(ethoxycarbonyl)‐3‐phenyl‐propyl]‐L‐alanyl‐L‐proline ( enalapril maleate ) was evaluated in a r and omized , double‐blind trial in 23 patients with mild low‐renin essential hypertension ranging in age from 32 to 70 yr ( 20 were black and 3 were white ) . All underwent a 4‐wk washout‐placebo phase and were then assigned to a dosing schedule of either 10 mg enalapril once daily , 5 mg enalapril twice daily , or placebo twice daily for 12 wk . Conditional on diastolic pressure , the dose was increased at 4‐wk intervals to a maximum of 40 mg daily or until control was achieved or the end of the study reached . At the end of the 12‐wk titration phase , there was a follow‐up period during which measurements were made after discontinuation of the medication . Mean supine diastolic pressure decreased from baseline ( 98.5 ± 2.6 mm Hg ) during the titration phase ( 86.3 ± 4.6 mm Hg ) in the group taking enalapril once daily . In three of the eight patients in the once‐daily group and five of eight in the twice‐daily group , supine diastolic pressures fell below 90 mm Hg . Neither supine nor st and ing systolic pressure nor st and ing diastolic pressure decreased significantly from pretreatment levels during enalapril once or twice daily . Heart rates measured after 5 min supine rest were not altered by enalapril . Enalapril induced inhibition of converting enzyme activity at all dose levels and with both dosing schedules . No adverse effect attributable to enalapril occurred during the study . The data indicate that once‐daily enalapril is safe and effective treatment for mild low‐renin essential hypertension", "Hypertension frequently complicates diabetes mellitus and is associated with an increased incidence of cardiovascular and microvascular complications . Angiotensin-I converting enzyme ( ACE ) inhibitors are effective antihypertensive agents and it has been suggested that they may improve glucose tolerance . We performed a double-blind , r and omized study comparing treatment for 8 weeks with cilazapril , a new ACE inhibitor , or placebo on metabolic variables in 22 hypertensive non-insulin-dependent diabetes mellitus ( NIDDM ) patients . At week 8 no significant changes in fasting plasma glucose , fasting plasma insulin , haemoglobin A1 and plasma lipids had occurred . The areas under the glucose [ placebo ( mean + /- SD ) : 10.7 + /- 3.27 and 10.6 + /- 2.53 ; cilazapril : 11.9 + /- 3.23 and 12.1 + /- 2.9 mmol/l per 180 min at 0 and 8 weeks , respectively ] and insulin curve [ placebo ( median and range ) : 47.4 ( 31.4 - 165.1 ) and 65.3 ( 16.8 - 190.8 ) ; cilazapril : 51.1 ( 23.8 - 132.0 ) and 57.6 ( 29.0 - 150.1 ) mU/l per 180 min at 0 and 8 weeks , respectively ] after a st and ardized oral liquid test meal were unaltered . A significant decrease in mean arterial blood pressure was observed after cilazapril ( 122 + /- 8.6 and 106 + /- 8.3 mmHg at 0 and 8 weeks , respectively ) , in contrast to placebo ( 122 + /- 6.7 and 120 + /- 6.9 mmHg at 0 and 8 weeks , respectively ) . In conclusion , cilazapril does not affect metabolic control in hypertensive NIDDM patients , whereas it effectively reduces blood pressure", "The renal effects of long‐term antihypertensive treatment with enalapril were evaluated in 34 subjects ( age , 53 yr ; range , 27 to 65 ) with mild , uncomplicated hypertension . After receiving placebo for 4 wk , subjects were r and omly assigned to groups receiving incremental doses of enalapril ( 10 , 20 , or 40 mg/day for 4 wk each ) in a single morning dose or two divided doses , or of placebo . One subject who received enalapril developed acute renal failure by the end of the study . There was no evidence of glomerular or tubular damage in the other subjects ; as measured by 24‐hr urinary protein excretion , urinary activity of N‐acetyl‐β‐D‐glucosaminidase , and uric acid clearance . During treatment with enalapril , renal plasma flow ( measured with 131l‐iodohippurate sodium ) and glomerular filtration rate increased by 12.1 % and 6.8 % . Changes in renal plasma flow correlated inversely with age and final mean arterial pressure and correlated positively with initial plasma renin activity of subjects . Except for an occasional idiosyncratic adverse reaction , enalapril is a safe and effective antihypertensive drug with the unique ability to increase renal function despite a fall in renal perfusion pressure ", "OBJECTIVE To test the antihypertensive and metabolic effects of lisinopril , 10 mg/d ( L ) ; hydrochlorothiazide , 12.5 and 25 mg/d ( H12.5 and H25 ) ; and its combination with lisinopril ( L/H12.5 and L/H25 ) against placebo in patients with mild to moderate ( stage I and stage II ) hypertension . DESIGN Multicenter , double-blind , placebo-controlled outpatient study of 12 weeks ' duration . PATIENTS After 4 weeks of single-blind placebo treatment , 505 patients whose sitting diastolic blood pressure was 100 to 114 mm Hg were r and omized into the study --467 patients completed it ( placebo , 71 ; L , 80 ; H12.5 , 79 ; H25 , 77 ; L/H12.5 , 79 ; and L/H25 , 81 ) . The patients were seen in the clinic every 2 weeks , where measurements of their sitting and upright blood pressure and heart rate were taken 24 + /- 2 hours after drug administration . Complete blood cell counts with differential cell counts , blood chemistry studies , urinalyses , and electrocardiograms were done at baseline and during the study . Roentgenograms were done once at baseline . RESULTS Compared with placebo , all drug regimens decreased sitting and upright blood pressure ( P sitting and upright heart rate . The greatest effect was obtained with the combinations of L/H12.5 and L/H25 . There was no difference between L/H12.5 and L/H25 or between H12.5 and H25 . There were no serious clinical side effects except cough , which was slightly higher with L , L/H12.5 , and L/H25 . The only metabolic side effects were in serum potassium level , which was lower with H25 ( P serum glucose level , which was higher with H25 and L/H25 ( P L , H12.5 , H25 , L/H12.5 , and L/H25 was effective and well tolerated ; ( 2 ) the best results were achieved with L/H12.5 and L/H25 ; ( 3 ) lower doses of hydrochlorothiazide either alone or in combination with lisinopril were equipotent with higher doses and were free of metabolic side effects", "The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics . Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P target SBP ( Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal", "The antihypertensive effect of captopril , metoprolol , and hydrochlorothiazide was compared in 23 non-insulin-dependent ( NIDDM ) diabetic patients less than or equal to 75 years of age , with borderline to moderate primary hypertension . In a double blind , placebo-controlled cross-over trial the patients were treated with 25 to 50 mg captopril , 50 to 100 mg metoprolol , 12.5 to 25 mg hydrochlorothiazide , and placebo , each given twice daily for 8 weeks . Antidiabetic treatment remained unchanged during the study . After receiving placebo for a 4 week run-in period , arterial blood pressure was 168/101 + /- 93/10 ( mean + /- SEM ) mm Hg . Diastolic blood pressure was lowered significantly during all active treatment periods compared to the placebo value of 97 + /- 2 mm Hg : captopril , 92 + /- 1 mm Hg ; metoprolol , 90 + /- 1 mm Hg ; hydrochlorothiazide , 91 + /- 1 mm Hg . Metabolic variables were not significantly altered by captopril and metoprolol , while hydrochlorothiazide treatment increased hemoglobin A1c from 7.5 + /- 0.3 to 8.2 + /- 0.4 % ( P less than .001 ) , decreased high-density lipoprotein-cholesterol from 1.19 + /- 0.08 to 1.10 + /- 0.06 mmol/L ( P less than .05 ) . Glomerular filtration rate , urinary albumin excretion , orthostatic blood pressure response , and digital systolic blood pressure in the lower limb remained unchanged during the active treatment periods . The frequency of subjective adverse effects was acceptable during active treatment and not significantly different compared to placebo . We conclude that antihypertensive treatment for 8 weeks with captopril or metoprolol in NIDDM patients is well-tolerated and causes no deterioration in metabolic control and kidney function , while hydrochlorothiazide causes a slight deterioration in glycemic control and lipid profile", "The time to peak antihypertensive effect and the trough‐to‐peak ratio were determined in 64 Caucasian patients ( 19 men , 45 women ) with mild to moderate hypertension [ supine diastolic blood pressure ( DBP ) 95 to 115 mmHg ] . They received placebo or fosinopril 10 , 20 , or 40 mg once daily for 4 weeks . The study consisted of a 4‐week placebo lead‐in , 4 weeks ' double‐blind treatment , and a 1‐week placebo washout period . Vital signs were determined biweekly before dosing , and blood pressures were measured every 1 to 2 h during two 27‐h periods at the beginning and end of treatment . After the first and last doses of all three regimens , the peak effect on blood pressure occurred 5 to 7 h after all three dosages . Neither peak nor trough blood pressure changes showed a clear dose‐response relationship . Trough to peak ratios for the first dose , corrected for placebo effects , were 79 % for fosinopril 10 mg , 48 % for fosinopril 20 mg , and 74 % for fosinopril 40 mg , and the trough‐to‐peak ratios for the last dose were 41 % for fosinopril 10 mg , 32 % for fosinopril 20 mg , and 44 % for fosinopril 40 mg . In the 38 responders among the 48 patients receiving fosinopril ( supine DBP decrease of at least 5 mmHg at 24 h postdose ) , trough‐to‐peak rations ranged from 50 to 81 % , and the range indicates that fosinopril is efficacious when administered once daily . Adverse effects were mild to moderate , and no patient discontinued treatment . Changes in the laboratory test results , electrocardiograms , or the results of physical examinations were unremarkable . Once‐daily fosinopril 10 , 20 , or 40 mg effectively and safely controlled blood pressure in patients with mild to moderate essential hypertension", "Cilazapril , an angiotensin converting enzyme ( ACE ) inhibitor with a long half-life , effectively reduced sitting diastolic blood pressure in patients with uncomplicated essential hypertension at dosages of 2.5 , 5.0 , and 10.0 mg/day , evaluated in a double-blind , placebo-controlled study . After a four-week placebo run-in period , 235 patients received either cilazapril or placebo for four weeks . At the end of the treatment period , significant decreases from baseline in sitting diastolic blood pressure were seen in all four groups ( mean decreases of 3.3 mm Hg with placebo and 6.4 , 9.2 and 8.3 mm Hg with 2.5 , 5.0 and 10.0 mg cilazapril , respectively ) . The cilazapril groups had significantly greater blood pressure reductions than did the placebo group ( p less than or equal to 0.02 ) . The 5.0 mg cilazapril dose was significantly more effective than the 2.5 mg dose ( p less than 0.03 ) . The response rate was notably greater in the cilazapril treatment groups than in the placebo group ( placebo , 27.5 % ; 2.5 mg cilazapril , 42.9 % ; 5.0 mg cilazapril 62.5 % ; 10.0 mg cilazapril , 50.0 % ) . Cilazapril was well tolerated at all three dosages", "The aim of this double-blind r and omized placebo-controlled study was to evaluate the antihypertensive and safety of fosinopril in mild essential hypertension . After a 2-week placebo period , patients received either placebo or fosinopril 20 mg , once daily . Thirty-four patients finished the study ( 18 patients in the placebo group and 16 patients in the fosinopril group ) . Systolic blood pressure decreased from 160.1 + /- 22.1 mmHg to 156.0 + /- 24.2 in the placebo group ( NS ) and from 151.8 + /- 14.0 mmHg to 141.5 + /- 14.5 in the fosinopril group ( p diastolic blood pressure decreased from 100.1 + /- 2.4 mmHg to 94.3 + /- 7.4 mmHg in the placebo group ( p fosinopril group ( p diastolic blood pressure was 5.7 mmHg in the placebo group and 12.6 mmHg in the fosinopril group ( p placebo group vs 56.2 % in the fosinopril group ( p biochemical parameters was seen between the two groups . Tolerance was good and no patients were withdrawn from the study for adverse events", "In this multicenter , placebo-controlled , double-blind , 4 x 3 factorial design study , 1,162 patients r and omized into 12 parallel groups received either placebo ( n = 97 ) , cilazapril ( CLZ 0.5 , 5 , or 10 mg ; n = 288 total ) , hydrochlorothiazide ( HCTZ 12.5 or 25 mg ; n = 198 total ) , or one of the six possible combinations of the two drugs ( n = 579 total ) given orally once daily for 4 weeks . The mean decrease from baseline in predose ( i.e. , 24 h postdose ) sitting diastolic blood pressure ( SDBP ) was statistically significantly ( p Synergistic antihypertensive effects were noted for the 5/12.5 mg CLZ/HCTZ combination therapy . The normalization ( SDBP CLZ/HCTZ combination was essentially additive with respect to the component monotherapies . The tolerability profile of the CLZ/HCTZ combination was similar to its respective components and comparable to placebo . The CLZ/HCTZ group reported low serum potassium ( K+ ) and high serum uric acid less frequently than the HCTZ group . Therefore , the CLZ/HCTZ combination ( 5 mg/12.5 mg ) is an option for hypertensive patients not responding to single drug CLZ therapy" ]

[ "Currently raloxifene , a selective estrogen receptor modulator , is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease . We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens ( CEEs ) . Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54 . 8+/-3.5 ( mean+/-SD ) years who entered this double-blind study and who were r and omly assigned to raloxifene hydrochloride 60 mg/d ( n=15 ) or 150 mg/d ( n=13 ) , placebo ( n=13 ) , or CEEs 0.625 mg/d ( n=15 ) . At baseline and after 6 , 12 , and 24 months of treatment , we assessed serum lipids , blood pressure , glucose metabolism , C-reactive protein , and various hemostatic parameters . Compared with placebo , both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L ( all P level of fibrinogen by 0.71 to 0.86 g/L ( all P high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen activator inhibitor-1 antigen by 30.6 to 48.6 ng/mL ( all P C-reactive protein by 1.0 mg/L at 6 months ( P prothrombin-derived fragment F1 + 2 by 0 . 79 nmol/L at 12 months ( P triglycerides by 0.33 to 0.56 mmol/L ( all P ) . Our findings suggest that in healthy postmenopausal women , raloxifene and estrogen monotherapy have similar beneficial effects on low density lipoprotein cholesterol and fibrinogen levels . These treatments differ , however , in their effects on high density lipoprotein cholesterol , triglycerides , and plasminogen activator inhibitor-1 and possibly in their effects on prothrombin fragment F1 + 2 and C-reactive protein", "CONTEXT The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a r and omized trial setting . OBJECTIVE To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 16 608 postmenopausal women , who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 ( average follow-up , 5.6 years ) . INTERVENTION One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURE Incident invasive cancer of the ovary and endometrium . RESULTS In 5.6 years of follow-up , there were 32 cases of invasive ovarian cancer , 58 cases of endometrial cancer , 1 case of nonendometrial uterine cancer , 13 cases of cervical cancer , and 7 cases of other gynecologic cancers . The hazard ratio ( HR ) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 ( 95 % confidence interval [ CI ] , 0.77 - 3.24 ) . The HR for endometrial cancer was 0.81 ( 95 % CI , 0.48 - 1.36 ) . No appreciable differences were found in the distributions of tumor histology , stage , or grade for either cancer site . The incidence of other gynecologic cancers was low and did not differ by r and omization assignment . More women taking estrogen plus progestin required endometrial biopsies ( 33 % vs 6 % ; P risk of ovarian cancer while producing endometrial cancer rates similar to placebo . The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen . These data provide additional support for caution in the use of continuous combined hormones", "Background — The Women ’s Health Initiative ( WHI ) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women . The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke . This report provides a thorough analysis of the stroke finding using the final results from the completed trial data base . Methods and Results — The WHI Estrogen Alone hormone trial is a multicenter , double-blind , placebo-controlled , r and omized clinical trial in 10 739 women aged 50 to 79 years who were given daily conjugated equine estrogen ( CEE ; 0.625 mg ; n=5310 ) or placebo ( n=5429 ) . During an average follow-up of 7.1 years , there were 168 strokes in the CEE group and 127 in the placebo group ; 80.3 % of strokes were ischemic . For all stroke the intention-to-treat hazard ratio [ HR ] ( 95 % CI ) for CEE versus placebo was 1.37 ( 1.09 to 1.73 ) . The HR ( 95 % CI ) was 1.55 ( 1.19 to 2.01 ) for ischemic stroke and 0.64 ( 0.35 , 1.18 ) for hemorrhagic stroke . The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk , including younger and more recently menopausal women and in women with prior or current use of statins or aspirin . Conclusions — CEE increases the risk of ischemic stroke in generally healthy postmenopausal women . The excess risk appeared to be present in all subgroups of women examined , including younger and more recently menopausal women . There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke", "Background Menopausal hormone therapy ( MHT ) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women , and whether MHT affects mood in younger women . The ancillary Cognitive and Affective Study ( KEEPS-Cog ) of the Kronos Early Estrogen Prevention Study ( KEEPS ) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women . Methods and Findings KEEPS , a r and omized , double-blinded , placebo-controlled clinical trial , was conducted at nine US academic centers . Of the 727 women enrolled in KEEPS , 693 ( 95.3 % ) participated in the ancillary KEEPS-Cog , with 220 women r and omized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens ( o-CEE ) plus 200 mg/d micronized progesterone ( m-P ) for the first 12 d of each month , 211 women r and omized to receive 50 μg/d transdermal estradiol ( t-E2 ) plus 200 mg/d m-P for the first 12 d of each month , and 262 women r and omized to receive placebo pills and patches . Primary outcomes included the Modified Mini-Mental State examination ; four cognitive factors : verbal learning/memory , auditory attention/working memory , visual attention/executive function , and speeded language /mental flexibility ; and a mood measure , the Profile of Mood States ( POMS ) . MHT effects were analyzed using linear mixed-effects ( LME ) models , which make full use of all available data from each participant , including those with missing data . Data from those with and without full data were compared to assess for potential biases result ing from missing observations . For statistically significant results , we calculated effect sizes ( ESs ) to evaluate the magnitude of changes . On average , participants were 52.6 y old , and 1.4 y past their last menstrual period . By month 48 , 169 ( 24.4 % ) and 158 ( 22.8 % ) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment ( 3MS and cognitive factors ) and mood evaluations ( POMS ) , respectively . However , because LME models make full use all available data , including data from women with missing data , 95.5 % of participants were included in the final analysis ( n = 662 in cognitive analyses , and n = 661 in mood analyses ) . To be included in analyses , women must have provided baseline data , and data from at least one post-baseline visit . The mean length of follow-up was 2.85 y ( st and ard deviation [ SD ] = 0.49 ) for cognitive outcomes and 2.76 ( SD = 0.57 ) for mood outcomes . No treatment-related benefits were found on cognitive outcomes . For mood , model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment , compared to women on placebo . The model estimate for the depression subscale was −5.36 × 10−2 ( 95 % CI , −8.27 × 10−2 to −2.44 × 10−2 ; ES = 0.49 , p ) and for the anxiety subscale was −3.01 × 10−2 ( 95 % CI , −5.09 × 10−2 to −9.34 × 10−3 ; ES = 0.26 , p 0.001 ) . Mood outcomes for women r and omized to t-E2 were similar to those for women on placebo . Importantly , the KEEPS-Cog results can not be extrapolated to treatment longer than 4 y. Conclusions The KEEPS-Cog findings suggest that for recently postmenopausal women , MHT did not alter cognition as hypothesized . However , beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE , but not with 4 y of t-E2 . The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles . Trial Registration Clinical Trials.gov NCT00154180 and", "OBJECTIVES To evaluate the effects of hormone replacement therapy ( HRT ) on lipids and lipoproteins in postmenopausal women with coronary artery disease . SETTING In this single-centre , controlled and r and omized study taking place in a tertiary referral clinic , patients were examined at baseline , and after 3 and 12 months . All analyses were performed examiner-blind . SUBJECTS Postmenopausal women ( n = 118 ) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease . INTERVENTIONS The women were r and omized to HRT , i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days , or to a control group . MAIN OUTCOMES Effects on lipids and lipoproteins . RESULTS After 3 months of unopposed oestradiol , triglycerides decreased significantly compared to the control group ( P = 0.006 ) . Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol ( P = 0.01 ) , concomitantly with a decrease in ApoA1 lipoproteins ( P = 0.007 ) . No other changes in lipids or lipoproteins were observed . After 12 months of therapy , no significant differences were observed between the two groups in lipid or lipoprotein levels . Concomitant statin treatment did not alter the main findings . CONCLUSIONS In postmenopausal women with established coronary artery disease in whom the majority is treated with statins , no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase . No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins", "Abstract —Postmenopausal hormone replacement therapy ( HRT ) is associated with low cardiovascular morbidity and mortality in epidemiological studies . Yet , no r and omized trial has examined whether HRT is effective for prevention of coronary heart disease ( CHD ) in women with increased risk . The objective of this study was to determine whether HRT can slow progression of atherosclerosis , measured as intima-media thickness ( IMT ) in carotid arteries . Carotid IMT is an appropriate intermediate end point to investigate clinical ly relevant effects on atherogenesis . This r and omized , controlled , observer-blind , clinical , single-center trial enrolled 321 healthy postmenopausal women with increased IMT in ≥1 segment of the carotid arteries . For a period of 48 weeks , subjects received either 1 mg/d 17&bgr;-estradiol continuously plus 0.025 mg gestodene for 12 days every month ( st and ard-progestin group ) , or 1 mg 17&bgr;-estradiol plus 0.025 mg gestodene for 12 days every third month ( low-progestin group ) , or no HRT . Maximum IMT in 6 carotid artery segments ( common , bifurcation , and internal , both sides ) was measured by B-mode ultrasound before and after intervention . HRT did not slow IMT progression in carotid arteries . Mean maximum IMT in the carotid arteries increased by 0.02±0.05 mm in the no HRT group and by 0.03±0.05 and 0.03±0.05 mm , respectively , in the HRT groups ( P > 0.2 ) . HRT significantly decreased LDL cholesterol , fibrinogen , and follicle-stimulating hormone . In conclusion , 1 year of HRT was not effective in slowing progression of sub clinical atherosclerosis in postmenopausal women at increased risk", "In a recent r and omized , double-blind , placebo-controlled trial of women with a history of venous thromboembolism ( VTE ) , we found that hormone replacement therapy ( HRT ) was associated with an early excess risk of recurrent thrombosis . The aims of the present study were to characterize the effects of HRT on coagulation in these women to eluci date the mechanism(s ) by which HRT increases the risk of thrombosis . The study comprised 140 women who were r and omized to receive continuous treatment for 24 months with once daily 2 mg 17-beta-estradiol plus 1 mg norethisterone acetate ( n = 71 ) or placebo ( n = 69 ) . HRT caused significant increases in prothrombin fragments 1 + 2 , thrombin-antithrombin complex , and D-Dimer after 3 months , but these changes were less pronounced on prolonged treatment . The increases in markers of activated coagulation was higher in those women who subsequently developed recurrent thrombosis , but was similar in carriers and non-carriers of the factor V Leiden mutation . HRT had no effects on fibrinogen and factor VIII . Activated factor VII , but not factor VII antigen , decreased significantly on HRT as compared with placebo . The coagulation inhibitors antithrombin , protein C , and TFPI , but not protein S , all showed significant sustained decreases in the HRT group as compared with placebo . Antithrombin and protein C decreased by 8 - 12 % on HRT , whereas TFPI activity decreased by 12 - 17 % and TFPI free antigen by 29 - 30 % . In multivariate analysis , only TFPI activity was a significant predictor for the increased activation of coagulation . We conclude that HRT was associated with early activation of coagulation , which corroborates the finding of an early risk of recurrent VTE . This activation may in part be explained by reduction in circulating anticoagulants", "CONTEXT The Women 's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks , including invasive breast cancer , exceeded benefits . Outst and ing issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography . OBJECTIVE To determine the relationship among estrogen plus progestin use , breast cancer characteristics , and mammography recommendations . DESIGN , SETTING , AND PARTICIPANTS Following a comprehensive breast cancer risk assessment , 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were r and omly assigned to receive combined conjugated equine estrogens ( 0.625 mg/d ) plus medroxyprogesterone acetate ( 2.5 mg/d ) or placebo from 1993 to 1998 at 40 clinical centers . Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter . MAIN OUTCOME MEASURES Breast cancer number and characteristics , and frequency of abnormal mammograms by estrogen plus progestin exposure . RESULTS In intent-to-treat analyses , estrogen plus progestin increased total ( 245 vs 185 cases ; hazard ratio [ HR ] , 1.24 ; weighted P invasive ( 199 vs 150 cases ; HR , 1.24 ; weighted P = .003 ) breast cancers compared with placebo . The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger ( mean [ SD ] , 1.7 cm [ 1.1 ] vs 1.5 cm [ 0.9 ] , respectively ; P = .04 ) and were at more advanced stage ( regional/metastatic 25.4 % vs 16.0 % , respectively ; P = .04 ) compared with those diagnosed in the placebo group . After 1 year , the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group ( 716 [ 9.4 % ] of 7656 ) compared with placebo group ( 398 [ 5.4 % ] of 7310 ; P estrogen plus progestin use increases incident breast cancers , which are diagnosed at a more advanced stage compared with placebo use , and also substantially increases the percentage of women with abnormal mammograms . These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis", "Objective To assess the effect of combined hormone replacement therapy ( HRT ) on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen ( n=1862 ) or placebo ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo : vasomotor symptoms ( P sexual functioning ( P sleep problems ( P combined HRT group reported hot flushes ( P night sweats ( P aching joints and muscles ( P=0.001 ) , insomnia ( P vaginal dryness ( P placebo group , but greater proportions reported breast tenderness ( P vaginal discharge ( P Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836", "Abstract Objective Endothelial dysfunction occurs early in the atherosclerotic disease process , often preceding clinical symptoms . Use of menopausal hormone treatment ( MHT ) to reduce cardiovascular risk is controversial . This study evaluated effects of 4 years of MHT on endothelial function in healthy , recently menopausal women . Methods Endothelial function was determined by pulse volume digital tonometry providing a reactive hyperemia index ( RHI ) in a subset of women enrolled in the Kronos Early Estrogen Prevention Study . RHI was measured before and annually after r and omization to daily oral conjugated equine estrogen ( oCEE , 0.45 mg ) , weekly transdermal 17β-estradiol ( tE2 , 50 μg ) each with intermittent progesterone ( 200 mg daily 12 days of the month ) or placebo pills and patch . Results At baseline , RHI averaged 2.39 ± 0.69 ( mean ± st and ard deviation ; n = 83 ) , and over follow-up did not differ significantly among groups : oCEE , 2.26 ± 0.48 ( n = 26 ) ; tE2 , 2.26 ± 0.45 ( n = 24 ) ; and placebo , 2.37 ± 0.37 ( n = 33 ) . Changes in RHI did not correlate with changes in traditional cardiovascular risk factors , but may inversely correlate with carotid intima medial thickness ( Spearman correlation coefficient ρ = −0.268 , p = 0.012 ) . Conclusion In this 4-year prospect i ve assessment of recently menopausal women , MHT did not significantly alter RHI when compared to placebo", "Background Although breast cancer risk is greater in users of estrogen – progestin than estrogen-only formulations of menopausal hormonal therapy , reports on their effects have been somewhat inconsistent . We investigated whether the timing of these therapies affected breast cancer incidence . Methods A total of 1 129 025 postmenopausal UK women provided prospect i ve information on hormonal therapy use and other factors relevant for breast cancer risk . We used Cox regression to estimate adjusted relative risks ( RRs ) of breast cancer in hormonal therapy users vs never users and calculated st and ardized incidence rates . All statistical tests were two-sided . Results During 4.05 million woman-years of follow-up , 15 759 incident breast cancers occurred , with 7107 in current users of hormonal therapy . Breast cancer incidence was increased in current users of hormonal therapy , returning to that of never users a few years after use had ceased . The relative risks for breast cancer in current users were greater if hormonal therapy was begun before or soon after menopause than after a longer gap ( Pheterogeneity estrogen-only and estrogen-progestin formulations ) . Among current users of estrogen-only formulations , there was little or no increase in risk if use began 5 years or more after menopause ( RR = 1.05 , 95 % confidence interval [ CI ] = 0.89 to 1.24 ) , but risk was statistically significantly increased if use began before or less than 5 years after menopause ( RR = 1.43 , 95 % CI = 1.35 to 1.51 ) . A similar pattern was observed among current users of estrogen – progestin formulations ( RR = 1.53 , 95 % CI = 1.38 to 1.70 , and RR = 2.04 , 95 % CI = 1.95 to 2.14 , respectively ) . At 50–59 years of age , annual st and ardized incidence rates for breast cancer were 0.30 % ( 95 % CI = 0.29 % to 0.31 % ) among never users of hormone therapy and 0.43 % ( 95 % CI = 0.42 % to 0.45 % ) and 0.61 % ( 95 % CI = 0.59 % to 0.64 % ) , respectively , among current users of estrogen-only and estrogen – progestin formulations who began use less than 5 years after menopause . Conclusions There was substantial heterogeneity in breast cancer risk among current users of hormonal therapy . Risks were greater among users of estrogen – progestin than estrogen-only formulations and if hormonal therapy started at around the time of menopause than later", "Objective To assess the effectiveness of enhanced communication therapy in the first four months after stroke compared with an attention control ( unstructured social contact ) . Design Externally r and omised , pragmatic , parallel , superiority trial with blinded outcome assessment . Setting Twelve UK hospital and community stroke services . Participants 170 adults ( mean age 70 years ) r and omised within two weeks of admission to hospital with stroke ( December 2006 to January 2010 ) whom speech and language therapists deemed eligible , and 135 carers . Interventions Enhanced , agreed best practice , communication therapy specific to aphasia or dysarthria , offered by speech and language therapists according to participants ’ needs for up to four months , with continuity from hospital to community . Comparison was with similarly re source d social contact ( without communication therapy ) from employed visitors . Outcome measures Primary outcome was blinded , functional communicative ability at six months on the Therapy Outcome Measure ( TOM ) activity subscale . Secondary outcomes ( unblinded , six months ) : participants ’ perceptions on the Communication Outcomes After Stroke scale ( COAST ) ; carers ’ perceptions of participants from part of the Carer COAST ; carers ’ wellbeing on Carers of Older People in Europe Index and quality of life items from Carer COAST ; and serious adverse events . Results Therapist and visitor contact both had good uptake from service users . An average 22 contacts ( intervention or control ) over 13 weeks were accepted by users . Impairment focused therapy was the approach most often used by the speech and language therapists . Visitors most often provided general conversation . In total , 81/85 of the intervention group and 72/85 of the control group completed the primary outcome measure . Both groups improved on the TOM activity subscale . The estimated six months group difference was not statistically significant , with 0.25 ( 95 % CI –0.19 to 0.69 ) points in favour of therapy . Sensitivity analyses that adjusted for chance baseline imbalance further reduced this difference . Per protocol analyses rejected a possible dilution of treatment effect from controls declining their allocation and receiving usual care . There was no added benefit of therapy on secondary outcome measures , subgroup analyses ( such as aphasia ) , or serious adverse events , although the latter were less common after intervention ( odds ratio 0.42 ( 95 % CI 0.16 to 1.1 ) ) . Conclusions Communication therapy had no added benefit beyond that from everyday communication in the first four months after stroke . Future research should evaluate reorganised services that support functional communication practice early in the stroke pathway . This project was funded by the NIHR Health Technology Assessment programme ( project No 02/11/04 ) and is published in full in Health Technology Assessment 2012;16(26):1 - 160 . Trial registration IS RCT", "In the 1990s , two r and omised clinical trials started in Sc and inavia addressing whether hormone replacement therapy ( HRT ) is safe for women with previous breast cancer . We report the findings of the safety analysis in HABITS ( hormonal replacement therapy after breast cancer -- is it safe ? ) , an open r and omised clinical trial with allocation to either HRT or best treatment without hormones . The main endpoint was any new breast cancer event . All analyses were done according to intention-to-treat . Until September , 2003 , 434 women were r and omised ; 345 had at least one follow-up report . After a median follow-up of 2.1 years , 26 women in the HRT group and seven in the non-HRT group had a new breast-cancer event . All women with an event in the HRT group and two of those in the non-HRT group were exposed to HRT and most women had their event when on treatment . We decided that these findings indicated an unacceptable risk for women exposed to HRT in the HABITS trial , and the trial was terminated on Dec 17 , 2003", "Background Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women 's age . Methods Postintervention follow-up was conducted with annual cognitive assessment s of two r and omized controlled clinical trial cohorts , beginning an average of 6 - 7 years after study medications were terminated : 1,376 women who had enrolled in the Women 's Health Initiative when aged 50 - 54 years and 2,880 who had enrolled when aged 65 - 79 years . Women had been r and omly assigned to 0.625mg/d conjugated equine estrogens ( CEE ) for those with prior hysterectomy ( mean 7.1 years ) , CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy ( mean 5.4 years ) , or matching placebos . Results Hormone therapy , when prescribed to women aged 50 - 54 years , had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function . When prescribed to older women , it was associated with long-term mean ( SE ) relative decrements ( st and ard deviation units ) in global cognitive function of 0.081 ( 0.029 ) , working memory of 0.070 ( 0.025 ) , and executive function of 0.054 ( 0.023 ) , all p Mean intervention effects were small ; however , the largest were comparable in magnitude to those seen during the trial 's active intervention phase . Conclusions CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment . If administered in older women , it results in small decrements in several cognitive domains that remain for many years", "CONTEXT The Women 's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens ( CEE ) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease . Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis . OBJECTIVE To determine the effects of CEE on breast cancers and mammographic findings . DESIGN , SETTING , AND PARTICIPANTS Following breast cancer risk assessment , 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were r and omized to CEE or placebo at 40 US clinical centers from 1993 through 1998 . Mammography screenings and clinical breast examinations were performed at baseline and annually . All breast cancers diagnosed through February 29 , 2004 , are included . INTERVENTION A dose of 0.625 mg/d of CEE or an identical-appearing placebo . MAIN OUTCOME MEASURES Breast cancer incidence , tumor characteristics , and mammogram findings . RESULTS After a mean ( SD ) follow-up of 7.1 ( 1.6 ) years , the invasive breast cancer hazard ratio ( HR ) for women assigned to CEE vs placebo was 0.80 ( 95 % confidence interval [ CI ] , 0.62 - 1.04 ; P = .09 ) with annualized rates of 0.28 % ( 104 cases in the CEE group ) and 0.34 % ( 133 cases in the placebo group ) . In exploratory analyses , ductal carcinomas ( HR , 0.71 ; 95 % CI , 0.52 - 0.99 ) were reduced in the CEE group vs placebo group ; however , the test for interaction by tumor type was not significant ( P = .054 ) . At 1 year , 9.2 % of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5 % in the placebo group ( P postmenopausal women with prior hysterectomy . However , treatment with CEE increases the frequency of mammography screening requiring short interval follow-up . Initiation of CEE should be based on consideration of the individual woman 's potential risks and benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "The authors further analyzed results from the Women 's Health Initiative r and omized trials ( 1993 - 2004 ) of conjugated equine estrogens , with or without medroxyprogesterone acetate , focusing on health benefits versus risks among women who initiated hormone therapy soon after menopause . Data from the Women 's Health Initiative observational study ( 1993 - 2004 ) were included in some analyses for additional precision . Results are presented here for incident coronary heart disease , stroke , venous thromboembolism , breast cancer , colorectal cancer , endometrial cancer , or hip fracture ; death from other causes ; a summary global index ; total cancer ; and total mortality . Hazard ratios for breast cancer and total cancer were comparatively higher ( P women who initiated hormone therapy soon after menopause , for both regimens . Among these women , use of conjugated equine estrogens appeared to produce elevations in venous thromboembolism and stroke and a reduction in hip fracture . Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism , stroke , and hip fracture but also included evidence of longer-term elevations in breast cancer , total cancer , and the global index . These analyses provide little support for the hypothesis of favorable effects among women who initiate postmenopausal estrogen use soon after menopause , either for coronary heart disease or for health benefits versus risk indices considered", "BACKGROUND Observational studies examining the role of estrogen in the risk of kidney stone formation have shown conflicting results . However , r and omized trial evidence on nephrolithiasis risk with estrogen therapy in postmenopausal women is lacking . METHODS We review ed the incidence of nephrolithiasis in the Women 's Health Initiative estrogen-alone and estrogen plus progestin trials conducted at 40 US clinical centers . A total of 10 739 postmenopausal women with hysterectomy were r and omized to receive 0.625 mg/d of conjugated equine estrogens ( CEE ) or placebo , and 16 608 postmenopausal women without hysterectomy were r and omized to receive placebo or estrogen plus progestin given as CEE plus medroxyprogesterone acetate ( 2.5 mg/d ) . The incidence of nephrolithiasis was determined for an average follow-up of 7.1 years for the CEE trial and 5.6 years for the estrogen plus progestin trial . RESULTS Baseline demographic characteristics and risk factors for nephrolithiasis were similar in the placebo and treatment arms . Estrogen therapy was associated with a significant increase in nephrolithiasis risk from 34 to 39 cases per 10 000 person-years ( hazard ratio , 1.21 ; 95 % confidence interval , 1.03 - 1.44 ) . Censoring data from women when they ceased to adhere to study medication increased the hazard ratio to 1.39 ( 95 % confidence interval , 1.08 - 1.78 ) . The increased nephrolithiasis risk was independent of progestin coadministration , and effects did not vary significantly according to prer and omization history of nephrolithiasis . CONCLUSIONS These data suggest that estrogen therapy increases the risk of nephrolithiasis in healthy postmenopausal women . These findings should be considered in decision making regarding postmenopausal estrogen use . The mechanisms underlying this higher susceptibility remain to be determined . Trial Registration clinical trials.gov Identifier : NCT0000611", "OBJECTIVES To determine whether small decrements in global cognitive function that conjugated equine estrogen ( CEE ) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains . DESIGN R and omized controlled clinical trial . SETTING Fourteen clinical centers of the Women 's Health Initiative . PARTICIPANTS Two thous and three hundred four women aged 65 to 80 free of probable dementia at enrollment . INTERVENTION CEE 0.625 mg/d with or without medroxyprogesterone acetate ( MPA , 10 mg/d ) and matching placebos . MEASUREMENTS Annual administrations of a battery of cognitive tests during and after the trial . RESULTS Assignment to CEE-based therapies was associated with small mean relative decrements in global cognitive function and several domain-specific cognitive functions during the trial , which largely persisted through up to 4 years after the trial . The strongest statistical evidence was for global cognitive function ( 0.07-st and ard deviation decrements during ( P=.007 ) and after ( P=.01 ) the trial . For domain-specific scores , the mean decrements were slightly smaller , were less significant , and tended to be larger for CEE-alone therapy . CONCLUSION CEE-based therapies , when initiated after the age of 65 , produce a small broad-based decrement in cognitive function that persists after their use is stopped , but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman . Differences in effects between cognitive domains suggest that more than one mechanism may be involved", "Recent observational studies suggest a 2 - 4 fold increased risk of venous thromboembolism ( VTE ) in women taking hormone replacement therapy ( HRT ) . The present study was started before publication of these studies , and the aim was to determine if HRT alters the risk of VTE in high risk women . The study was a r and omized . double-blind , and placebo-controlled clinical trial with a double-triangular sequential design . Females with previously verified VTE were r and omized to 2 mg estradiol plus 1 mg norethisterone acetate , 1 tablet daily ( n = 71 ) or placebo ( n = 69 ) . The primary outcome was recurrent deep venous thrombosis ( DVT ) or pulmonary embolism ( PE ) . Between 1996 and 1998 a total of 140 women were included . The study was terminated prematurely based on the results of circumstantial evidence emerging during the trial . Eight women in the HRT group and one woman in the placebo group developed VTE . The incidence of VTE was 10.7 % in the HRT group and 2.3 % in the placebo group . In the HRT group , all events happened within 261 days after inclusion . The sequential design did not stop the study , but strongly indicated a difference between the two groups . Our data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT . This treatment should therefore be avoided in this patient group if possible . The results also support those of recent epidemiological studies , which also indicate increased risk of VTE in non-selected female population s during HRT", "IMPORTANCE The use of menopausal hormone therapy ( HT ) continues in clinical practice , but reports are conflicting concerning the longer-term breast cancer effects of relatively short-term use . OBJECTIVE To report the longer-term influence of menopausal HT on breast cancer incidence in the 2 Women 's Health Initiative ( WHI ) r and omized clinical trials . DESIGN , SETTING , AND PARTICIPANTS A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers from 1993 to 1998 and followed up for a median of 13 years through September 2010 . INTERVENTIONS A total of 16,608 women with a uterus were r and omized to conjugated equine estrogens ( 0.625 mg/d [ estrogen ] ) plus medroxyprogesterone acetate ( 2.5 mg/d [ progestin ] ) ( E + P ) or placebo with a median intervention duration of 5.6 years , and 10,739 women with prior hysterectomy were r and omized to conjugated equine estrogens alone ( 0.625 mg/d ) or placebo with a median intervention duration of 7.2 years . MAIN OUTCOMES AND MEASURES Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials . RESULTS In the E + P trial , hazard ratios ( HRs ) for the influence of combined HT on breast cancer were lower than 1 for 2 years ( HR , 0.71 ; 95 % CI , 0.47 - 1.08 ) and steadily increased throughout intervention , becoming significantly increased for the entire intervention phase ( HR , 1.24 ; 95 % CI , 1.01 - 1.53 ) . In the early postintervention phase ( within 2.75 years from intervention ) , there was a sharp decrease in breast cancer incidence in the combined HT group , though the HR remained higher than 1 ( HR , 1.23 ; 95 % CI , 0.90 - 1.70 ) . During the late postintervention phase ( requiring patient re-consent ) , the HR for breast cancer risk remained higher than 1 through 5.5 years ( median ) of additional follow-up ( HR , 1.37 ; 95 % CI , 1.06 - 1.77 ) . In the estrogen alone trial , the HR for invasive breast cancer risk was lower than 1 throughout the intervention phase ( HR , 0.79 ; 95 % CI , 0.61 - 1.02 ) and remained lower than 1 in the early postintervention phase ( HR , 0.55 ; 95 % CI , 0.34 - 0.89 ) , but risk reduction was not observed during the late postintervention follow-up ( HR , 1.17 ; 95 % CI , 0.73 - 1.87 ) . Characteristics of breast cancers diagnosed during early and late postintervention phases differed in both trials . CONCLUSIONS AND RELEVANCE In the E + P trial , the higher breast cancer risk seen during intervention was followed by a substantial drop in risk in the early postintervention phase , but a higher breast cancer risk remained during the late postintervention follow-up . In the estrogen alone trial , the lower breast cancer risk seen during intervention was sustained in the early postintervention phase but was not evident during the late postintervention follow-up", "BACKGROUND Following the release of the 2002 report of the Women 's Health Initiative ( WHI ) trial of estrogen plus progestin , the use of menopausal hormone therapy in the United States decreased substantially . Subsequently , the incidence of breast cancer also dropped , suggesting a cause- and -effect relation between hormone treatment and breast cancer . However , the cause of this decrease remains controversial . METHODS We analyzed the results of the WHI r and omized clinical trial -- in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo-- and examined temporal trends in breast-cancer diagnoses in the WHI observational- study cohort . Risk factors for breast cancer , frequency of mammography , and time-specific incidence of breast cancer were assessed in relation to combined hormone use . RESULTS In the clinical trial , there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study , but the number of diagnoses increased over the course of the 5.6-year intervention period . The elevated risk decreased rapidly after both groups stopped taking the study pills , despite a similar frequency of mammography . In the observational study , the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group , but this difference in incidence decreased rapidly in about 2 years , coinciding with year-to-year reductions in combined hormone use . During this period , differences in the frequency of mammography between the two groups were unchanged . CONCLUSIONS The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography", "BACKGROUND While progestin addition to estrogen mitigates endometrial cancer risk , the magnitude of the effect on incidence , specific endometrial cancer histologies , and endometrial cancer mortality remains unsettled . These issues were assessed by analyses after extended follow-up of the Women 's Health Initiative ( WHI ) r and omized clinical trial evaluating continuous combined estrogen plus progestin use . METHODS The WHI enrolled 16 608 postmenopausal women into a r and omly assigned , double-blind , placebo-controlled trial . Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were r and omly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate ( n = 8506 ) as a single pill or matching placebo ( n = 8102 ) . Follow-up beyond the original trial completion date required reconsent , obtained from 12 788 ( 83 % ) of surviving participants . Analyses were by intent-to-treat . All statistical tests were two-sided . RESULTS After 5.6 years ' median intervention and 13 years ' median cumulative follow-up , there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group ( 66 vs 95 case patients , yearly incidence , 0.06 % vs 0.10 % ; hazard ratio [ HR ] = 0.65 , 95 % confidence interval [ CI ] = 0.48 to 0.89 , P = .007 ) . While there were somewhat fewer endometrial cancers during intervention ( 25 vs 30 , respectively ; HR = 0.77 , 95 % CI = 0.45 to 1.31 ) , the difference became statistically significant postintervention ( 41 vs 65 , respectively ; HR = 0.59 , 95 % CI = 0.40 to 0.88 , P = .008 ) , but hazard ratios did not differ between phases ( P difference = .46 ) . There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group ( 5 vs 11 deaths , HR = 0.42 , 95 % CI = 0.15 to 1.22 ) . CONCLUSION In postmenopausal women , continuous combined estrogen plus progestin decreases endometrial cancer incidence", "Background : In separate Women 's Health Initiative r and omized trials , combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not . We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial . Participants and Methods : 10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were r and omized to conjugated equine estrogens ( 0.625 mg/d ) or matching placebo . Colorectal cancer incidence was a component of the monitoring global index of the study but was not a primary study endpoint . Colorectal cancers were verified by central medical record and pathology report review . Bowel exam frequency was not protocol defined , but information on their use was collected . Results : After a median 7.1 years , there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group [ hazard ratio , 1.12 ; 95 % confidence interval ( 95 % CI ) , 0.77 - 1.63 ] . Tumor size , stage , and grade were comparable in the two r and omization groups . Bowel exam frequency was also comparable in the two groups . The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34 % compared with 30 % in the placebo group ( hazard ratio , 1.34 ; 95 % CI , 0.58 - 3.19 ) . Conclusions : In contrast to the preponderance of observational studies , conjugated equine estrogens in a r and omized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis . ( Cancer Epidemiol Biomarkers Prev 2008;17(10):2609–18", "Recent studies suggest that low‐dose oral contraceptives may cause acquired resistance to activated protein C ( APC ) . The aims of this study were to determine whether hormone replacement therapy ( HRT ) may also induce acquired APC resistance and to study the effects of APC resistance on the risk of recurrent thrombosis . The patients comprised 140 females with at least one previous venous thromboembolism ( VTE ) , who were r and omized to receive continuous treatment with 2 mg 17‐β‐oestradiol and 1 mg norethisterone acetate ( n = 71 ) or placebo ( n = 69 ) . Normalized APC sensitivity ratios ( nAPCsr ) were calculated by measurement of the effect of APC on thrombin generation in plasma collected at baseline and after 3 months of treatment . Of the 140 women , 121 had plasma sample s collected both at baseline and after 3 months . The nAPCsr increased significantly ( P 59 ) . The baseline nAPCsr as well as the increase in nAPCsr associated with HRT use was not higher in the five women who subsequently developed recurrent VTE . Free protein S and free TFPI were both important parameters for the acquired APC resistant phenotype . We conclude that HRT diminishes the efficacy by which APC downregulates in‐vitro thrombin formation in a similar fashion to that observed with low‐dose oral contraceptives , but the increase in nAPCsr alone is not sufficient to explain the increased risk of VTE associated with use of HRT ", "The Women 's Health Initiative ( WHI ) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women , including cancer , cardiovascular disease , and osteoporotic fractures . The WHI was initiated in 1992 , with a planned completion date of 2007 . Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial ( CT ) that will include about 64,500 women or an observational study ( OS ) that will include about 100,000 women . The CT is design ed to allow r and omized controlled evaluation of three distinct interventions : a low-fat eating pattern , hypothesized to prevent breast cancer and colorectal cancer and , secondarily , coronary heart disease ; hormone replacement therapy , hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and , secondarily , to reduce the risk of hip and other fractures , with increased breast cancer risk as a possible adverse outcome ; and calcium and vitamin D supplementation , hypothesized to prevent hip fractures and , secondarily , other fractures and colorectal cancer . Overall benefit-versus-risk assessment is a central focus in each of the three CT components . Women are screened for participation in one or both of the components -- dietary modification ( DM ) or hormone replacement therapy (HRT)--of the CT , which will r and omize 48,000 and 27,500 women , respectively . Women who prove to be ineligible for , or who are unwilling to enroll in , these CT components are invited to enroll in the OS . At their 1-year anniversary of r and omization , CT women are invited to be further r and omized into the calcium and vitamin D ( CaD ) trial component , which is projected to include 45,000 women . The average follow-up for women in either CT or OS is approximately 9 years . Concerted efforts are made to enroll women of racial and ethnic minority groups , with a target of 20 % of overall enrollment in both the CT and OS . This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component . Some detail is provided on specific study design choices , including eligibility criteria , recruitment strategy , and sample size , with attention to the partial factorial design of the CT . Some aspects of the CT monitoring approach are also outlined . The scientific and logistic complexity of the WHI implies particular leadership and management challenges . The WHI organization and committee structure employed to respond to these challenges is also briefly described", "UNLABELLED Further analyses from the Women 's Health Initiative estrogen trial shows that CEE reduced fracture risk . The fracture reduction at the hip did not differ appreciably among risk strata . These data do not support overall benefit over risk , even in women at highest risk for fracture . INTRODUCTION The Women 's Health Initiative provided evidence that conjugated equine estrogen ( CEE ) can significantly reduce fracture risk in postmenopausal women . Additional analysis of the effects of CEE on BMD and fracture are presented . MATERIAL S AND METHODS Postmenopausal women 50 - 79 years of age with hysterectomy were r and omized to CEE 0.625 mg daily ( n = 5310 ) or placebo ( n = 5429 ) and followed for an average 7.1 years . Fracture incidence was assessed by semiannual question naire and verified by adjudication of radiology reports . BMD was measured in a subset of women ( N = 938 ) at baseline and years 1 , 3 , and 6 . A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk . RESULTS CEE reduced the risk of hip ( hazard ratio [ HR ] , 0.65 ; 95 % CI , 0.45 - 0.94 ) , clinical vertebral ( HR , 0.64 ; 95 % CI , 0.44 - 0.93 ) , wrist/lower arm ( HR , 0.58 ; 95 % CI , 0.47 - 0.72 ) , and total fracture ( HR , 0.71 ; 95 % CI , 0.64 - 0.80 ) . This effect did not differ among strata according to age , oophorectomy status , past hormone use , race/ethnicity , fall frequency , physical activity , or fracture history . Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms ( HR , 0.86 ; 95 % CI , 0.68 - 1.08 ) . CEE also provided modest but consistent positive effects on BMD . The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk ( lowest risk : HR , 0.81 ; 95 % CI , 0.62 - 1.05 ; mid risk : HR , 1.09 ; 95 % CI , 0.92 - 1.30 ; highest risk : HR , 1.04 ; 95 % CI , 0.88 - 1.23 ; interaction , p = 0.42 ) . CONCLUSIONS CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women . Even among the women with the highest risk for fractures , when considering the effects of estrogen on other important health outcomes , a summary of the burden of monitored effects does not indicate a significant net benefit", "CONTEXT The Heart and Estrogen/progestin Replacement Study ( HERS ) found no overall reduction in risk of coronary heart disease ( CHD ) events among postmenopausal women with CHD . However , in the hormone group , findings did suggest a higher risk of CHD events during the first year , and a decreased risk during years 3 to 5 . OBJECTIVE To determine if the risk reduction observed in the later years of HERS persisted and result ed in an overall reduced risk of CHD events with additional years of follow-up . DESIGN AND SETTING R and omized , blinded , placebo-controlled trial of 4.1 years ' duration ( HERS ) and subsequent unblinded follow-up for 2.7 years ( HERS II ) conducted at outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS ; 2321 women ( 93 % of those surviving ) consented to follow-up in HERS II . INTERVENTION Participants were r and omly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate ( n = 1380 ) , or placebo ( n = 1383 ) during HERS ; open-label hormone therapy was prescribed at personal physicians ' discretion during HERS II . The proportions with at least 80 % adherence to hormones declined from 81 % ( year 1 ) to 45 % ( year 6 ) in the hormone group , and increased from 0 % ( year 1 ) to 8 % ( year 6 ) in the placebo group . MAIN OUTCOME MEASURES The primary outcome was nonfatal myocardial infa rct ion and CHD death . Secondary cardiovascular events were coronary revascularization , hospitalization for unstable angina or congestive heart failure , nonfatal ventricular arrhythmia , sudden death , stroke or transient ischemic attack , and peripheral arterial disease . RESULTS There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS , HERS II , or overall . The unadjusted relative hazard ( RH ) for CHD events in HERS was 0.99 ( 95 % confidence interval [ CI ] , 0.81 - 1.22 ) ; HERS II , 1.00 ( 95 % CI , 0.77 - 1.29 ) ; and overall , 0.99 ( 0.84 - 1.17 ) . The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups ( RH , 0.97 ; 95 % CI , 0.82 - 1.14 ) , and in analyses restricted to women who were adherent to r and omized treatment assignment ( RH , 0.96 ; 95 % CI , 0.77 - 1.19 ) . CONCLUSIONS Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up . After 6.8 years , hormone therapy did not reduce risk of cardiovascular events in women with CHD . Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD", "OBJECTIVE To evaluate the effect of a 17beta-estradiol(E2)/norgestimate ( NGM ) HRT regimen , which provides constant estrogen in combination with pulsed progestin administration , on endometrial histology in healthy postmenopausal women 40 to 65 years of age who had experienced natural menopause at least 12 months before the start of the study . METHODS A total of 1,253 postmenopausal women were r and omized to receive either continuous 1 mg E2 , or constant estrogen , pulsed progestin regimens of 1 mg E2/30 microg NGM , 1 mg E2/90 microg NGM , or 1 mg E2/180 microg NGM ( 3 days on , 3 days off ) in a 12-month , multicenter , double-blind study . Endometrial biopsies were obtained pre- and post-treatment , and were evaluated by at least 2 ( if required , by 3 ) pathologists who were blinded with respect to treatment and to each other 's diagnosis . RESULTS At the end of the study , no cases of endometrial hyperplasia were diagnosed in subjects who received E2 1 mg/NGM 90 microg or E21 mg/NGM 180 microg , whereas 74 ( 28 % ) and 16 ( 6 % ) cases of endometrial hyperplasia were diagnosed in subjects who received continuous E2 1 mg and E2 1 mg/NGM 30 microg , respectively . A dose-related endometrial response to NGM was apparent ( P percentage of patients with inactive/atrophic endometrium increased with NGM dose . CONCLUSION The results of this study support the safety and efficacy of this unique HRT regimen and suggest that the minimal NGM dose required to protect the endometrium from hyperplasia in a pulsed progestin regimen consisting of continuous E2 1 mg is 90 microg", "PURPOSE As the influence of estrogen alone on breast cancer detection is not established , we examined this issue in the Women 's Health Initiative trial , which r and omly assigned 10,739 postmenopausal women with prior hysterectomy to conjugated equine estrogen ( CEE ; 0.625 mg/d ) or placebo . METHODS Screening mammography and breast exams were performed at baseline and annually . Breast biopsies were based on clinical findings . Effects of CEE alone on breast cancer detection were determined by using receiver operating characteristic ( ROC ) analyses of mammogram performance . RESULTS After a 7.1-year mean follow-up , fewer invasive breast cancers were diagnosed in the CEE than in the placebo group , but the difference was not statistically significant . Use of CEE alone increased mammograms with short-interval follow-up recommendations ( cumulative , 39.2 % v 29.6.3 % ; P abnormal mammograms ( ie , those suggestive of or highly suggestive of malignancy ; cumulative , 7.3 % v 7.0 % ; P = .41 ) . Breast biopsies were more frequent in the CEE group ( cumulative , 12.5 % v 10.7 % ; P = .004 ) and less commonly diagnosed as cancer ( 8.9 % v 15.8 % , respectively , with positive biopsies ; P = .04 ) . Mammographic breast cancer detection in the CEE group was significantly compromised only in the early years of use . CONCLUSION CEE alone use for 5 years results in approximately one in 11 and one in 50 women having otherwise avoidable mammograms with short-interval follow-up recommendations or breast biopsies , respectively . Although the breast biopsies on CEE were less commonly diagnosed as cancer , breast cancer detection was not substantially compromised . These findings differ from estrogen-plus-progestin use , for which significantly increased abnormal mammograms and a compromise in breast cancer detection are seen", "BACKGROUND The effect of combined hormone therapy on breast cancer detection is not established . METHODS We examined the effect of combined hormone therapy on breast cancer detection in the Women 's Health Initiative trial , which r and omized 16,608 postmenopausal women to receive conjugated equine estrogens ( 0.625 mg/d ) plus medroxyprogesterone acetate ( 2.5 mg/d ) or placebo . Mammography and breast examinations were performed at baseline and annually per protocol , with breast biopsies based on clinical findings . The effects of conjugated equine estrogens plus medroxyprogesterone acetate on breast cancer detection was determined throughout 5.6 years of intervention using receiver operating characteristic analyses to evaluate mammography results . RESULTS Conjugated equine estrogens plus medroxyprogesterone acetate increased the cumulative frequency of mammograms with abnormalities vs placebo ( 35.0 % vs 23.0 % ; P sensitivity for cancer detection and increased cumulative breast biopsy frequency ( 10.0 % vs 6.1 % ; P breast cancers were significantly increased and were diagnosed at higher stages in the combined hormone group , biopsies in that group less frequently diagnosed cancer ( 14.8 % vs 19.6 % ; P = .006 ) . After discontinuation of combined hormone therapy , its adverse effect on mammograms modulated but remained significantly different from that of placebo for at least 12 months ( P estrogens plus medroxyprogesterone acetate for approximately 5 years result ed in more than 1 in 10 and 1 in 25 women having otherwise avoidable mammogram abnormalities and breast biopsies , respectively , and compromised the diagnostic performance of both . This adverse effect on breast cancer detection should be incorporated into risk-benefit discussion s with women considering even short-term combined hormone therapy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "The postmenopausal hormone therapy ( PHT ) component of the Women ’s Health Initiative ( WHI ) is composed of two r and omized , placebo-controlled , double-blind trials in postmenopausal women aged 50 to 79 years at initial screening , testing the effects of estrogen alone ( E-alone ) and estrogen plus progestin ( E P ) on coronary heart disease ( CHD ) as the primary outcome , hip and other fractures and colorectal cancer as secondary outcomes , and pulmonary embolism , breast and endometrial cancers as potential risks . The design and rationale of the PHT trials , including general eligibility and exclusion criteria and considerations regarding sample size and statistical power , have been described previously ( 1 ) . Postmenopausal hormones have been initiated in menopausal women for the treatment of vasomotor symptoms , mood disturbances , vaginal dryness , and prevention of rapid bone loss for several decades . Despite a paucity of data on effects of initiating hormone use in older women , postmenopausal hormones have also been promoted for the prevention of CHD , osteoporotic fractures , and other diseases that occur years after menopause ( 2 ) . It is generally recommended ( 2 ) that women with a uterus be prescribed a combination of estrogen and progestin to prevent", "OBJECTIVE In older women , higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes . We examined whether the effect of postmenopausal hormone therapy ( HT ) on cognitive impairment incidence differs depending on type 2 diabetes . RESEARCH DESIGN AND METHODS The Women ’s Health Initiative ( WHI ) r and omized clinical trials assigned women to HT ( 0.625 mg/day conjugated equine estrogens with or without [ i.e. , unopposed ] 2.5 mg/day medroxyprogesterone acetate ) or matching placebo for an average of 4.7–5.9 years . A total of 7,233 women , aged 65–80 years , were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment ( mild cognitive impairment or dementia ) . RESULTS Through a maximum of 18 years of follow-up , women with diabetes had increased risk of probable dementia ( hazard ratio [ HR ] 1.54 [ 95 % CI 1.16–2.06 ] ) and cognitive impairment ( HR 1.83 [ 1.50–2.23 ] ) . The combination of diabetes and r and om assignment to HT increased their risk of dementia ( HR 2.12 [ 1.47–3.06 ] ) and cognitive impairment ( HR 2.20 [ 1.70–2.87 ] ) compared with women without these conditions , interaction P = 0.09 and P = 0.08 . These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens . CONCLUSIONS These analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women . The role estrogen plays in suppressing non – glucose-based energy sources in the brain may explain this interaction", "BACKGROUND Case-control studies have reported that exogenous estrogen use is associated with increased risk of skin cancer . The effects of menopausal hormone therapy on incidence of nonmelanoma skin cancer and melanoma were evaluated in post hoc analyses of the Women 's Health Initiative r and omized placebo-controlled hormone therapy trials of combined estrogen plus progestin ( E + P ) and estrogen only ( E-alone ) . METHODS Postmenopausal women aged 50 - 79 years were r and omly assigned to conjugated equine estrogen ( 0.625 mg/d ) plus medroxyprogesterone acetate ( 2.5 mg/d ) or placebo in the E + P trial if they had an intact uterus ( N = 16,608 ) or to conjugated equine estrogen alone or placebo in the E-alone trial if they had a hysterectomy ( N = 10,739 ) ; the mean follow-up was 5.6 and 7.1 years , respectively . Incident nonmelanoma skin cancers ( n = 980 [ E + P trial ] ; n = 820 [ E-alone trial ] ) and melanomas ( n = 57 [ E + P trial ] ; n = 38 [ E-alone trial ] ) were ascertained by self-report . Incident cases of cutaneous malignant melanoma were confirmed by physician review of medical records . Incidences of nonmelanoma skin cancer and melanoma were compared between the two r and omization groups within each trial using hazard ratios ( HRs ) , with corresponding 95 % confidence intervals ( CIs ) and Wald statistic P values from Cox proportional hazards models . All statistical tests were two-sided . RESULTS Rates of incident nonmelanoma skin cancer and melanoma were similar between the active hormone ( combined analysis of E + P and E-alone ) and placebo groups ( nonmelanoma skin cancer : HR = 0.98 , 95 % CI = 0.89 to 1.07 ; melanoma : HR = 0.92 , 95 % CI = 0.61 to 1.37 ) . Results were similar for the E + P and E-alone trials when analyzed individually . CONCLUSIONS Menopausal hormone therapy did not affect overall incidence of nonmelanoma skin cancer or melanoma . These findings do not support a role of menopausal estrogen , with or without progestin , in the development of skin cancer in postmenopausal women", "Evidence from animal , human cross-sectional , case-control , and prospect i ve studies indicate that hormone replacement therapy ( HRT ) is a promising treatment to delay the onset of symptoms of dementia . The Women 's Health Initiative Memory Study ( WHIMS ) is the first double-masked , r and omized , placebo-controlled , long-term clinical trial design ed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older . WHIMS , an ancillary study to the Women 's Health Initiative ( WHI ) funded by the National Institutes of Health , will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI . The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period . Participants will be followed annually for 6 years , receiving cognitive assessment s via the Modified Mini-Mental State ( 3MS ) Examination . Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation . Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia . WHIMS is design ed to provide more than 80 % statistical power to detect a 40 % reduction in the rate of all-cause dementia , an effect that could have profound public health implication s for older women 's health and functioning", "Introduction Paradoxically , a breast cancer risk reduction with conjugated equine estrogens ( CEE ) and a risk elevation with CEE plus medroxyprogesterone acetate ( CEE + MPA ) were observed in the Women ’s Health Initiative ( WHI ) r and omized controlled trials . The effects of hormone therapy on serum sex hormone levels , and on the association between baseline sex hormones and disease risk , may help explain these divergent breast cancer findings . Methods Serum sex hormone concentrations were measured for 348 breast cancer cases in the CEE + MPA trial and for 235 cases in the CEE trial along with corresponding pair-matched controls , nested within the WHI trials of healthy postmenopausal women . Association and mediation analyses , to examine the extent to which sex hormone levels and changes can explain the breast cancer findings , were conducted using logistic regression . Results Following CEE treatment , breast cancer risk was associated with higher concentrations of baseline serum estrogens , and with lower concentrations of sex hormone binding globulin . However , following CEE + MPA , there was no association of breast cancer risk with baseline sex hormone levels . The sex hormone changes from baseline to year 1 provided an explanation for much of the reduced breast cancer risk with CEE . Specifically , the treatment odds ratio ( 95 % confidence interval ) increased from 0.71 ( 0.43 , 1.15 ) to 0.92 ( 0.41 , 2.09 ) when the year 1 measures were included in the logistic regression analysis . In comparison , the CEE + MPA odds ratio was essentially unchanged when these year 1 measures were included . Conclusions Breast cancer risk remains low following CEE use among women having favorable baseline sex hormone profiles , but CEE + MPA evidently produces a breast cancer risk for all women similar to that for women having an unfavorable baseline sex hormone profile . These patterns could reflect breast ductal epithelial cell stimulation by CEE + MPA that is substantially avoided with CEE , in conjunction with relatively more favorable effects of either regimen following a sustained period of estrogen deprivation . These findings may have implication s for other hormone therapy formulations and routes of delivery . Trial registration clinical trials.gov identifier : NCT00000611", "BACKGROUND Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events . In contrast , in a recent clinical trial of women with coronary disease , a subgroup analysis demonstrated increased risk during the early months of therapy . Because higher levels of inflammation factors predict vascular disease outcomes , the effect of hormones on these factors is of interest . METHODS AND RESULTS Four inflammation-sensitive factors , C-reactive protein , soluble E-selectin , von Willebr and factor antigen , and coagulation factor VIIIc were measured at baseline , 12 , and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions ( PEPI ) Trial , a r and omized , placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors . Compared with placebo , all 4 active preparations result ed in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin ( P=0.0001 ) . There were no effects of treatment on concentrations of von Willebr and factor or factor VIIIc . There were no differences in effects among treatment arms . Relative to placebo , when combining active treatment arms , final concentrations of C-reactive protein were 85 % higher whereas E-selectin was 18 % lower compared with baseline . CONCLUSIONS Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein . Such an effect may be related to adverse early effects of estrogen therapy . In contrast , hormones reduced the concentration of soluble E-selectin , and this might be considered an anti-inflammatory effect . Because PEPI was not design ed to assess clinical endpoints , studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed", "CONTEXT In the Women 's Health Initiative r and omized , placebo-controlled trial of estrogen plus progestin , after a mean intervention time of 5.6 ( SD , 1.3 ) years ( range , 3.7 - 8.6 years ) and a mean follow-up of 7.9 ( SD , 1.4 ) years , breast cancer incidence was increased among women who received combined hormone therapy . Breast cancer mortality among participants in the trial has not been previously reported . OBJECTIVE To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 ( SD , 2.7 ) years , through August 14 , 2009 . DESIGN , SETTING , AND PARTICIPANTS A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were r and omly assigned to receive combined conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , or placebo pill . After the original trial completion date ( March 31 , 2005 ) , reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 ( 83 % ) of the surviving participants . MAIN OUTCOME MEASURES Invasive breast cancer incidence and breast cancer mortality . RESULTS In intention-to-treat analyses including all r and omized participants and censoring those not consenting to additional follow-up on March 31 , 2005 , estrogen plus progestin was associated with more invasive breast cancers compared with placebo ( 385 cases [ 0.42 % per year ] vs 293 cases [ 0.34 % per year ] ; hazard ratio [ HR ] , 1.25 ; 95 % confidence interval [ CI ] , 1.07 - 1.46 ; P = .004 ) . Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive ( 81 [ 23.7 % ] vs 43 [ 16.2 % ] , respectively ; HR , 1.78 ; 95 % CI , 1.23 - 2.58 ; P = .03 ) . There were more deaths directly attributed to breast cancer ( 25 deaths [ 0.03 % per year ] vs 12 deaths [ 0.01 % per year ] ; HR , 1.96 ; 95 % CI , 1.00 - 4.04 ; P = .049 ) as well as more deaths from all causes occurring after a breast cancer diagnosis ( 51 deaths [ 0.05 % per year ] vs 31 deaths [ 0.03 % per year ] ; HR , 1.57 ; 95 % CI , 1.01 - 2.48 ; P = .045 ) among women who received estrogen plus progestin compared with women in the placebo group . CONCLUSIONS Estrogen plus progestin was associated with greater breast cancer incidence , and the cancers are more commonly node-positive . Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "Objective To study whether oestrongen replacement therapy has an effect on autonomic haemodynamic control in postmenopausal women", "PURPOSE To determine the effect of estrogen replacement therapy ( ERT ) on recurrence rate and survival in women who have undergone surgery for stage I or II endometrial cancer . PATIENTS AND METHODS After surgery , eligible patients were allocated to therapy with ERT or placebo after undergoing hysterectomy with or without pelvic and aortic nodal sampling . Planned duration of hormonal versus placebo treatment was 3 years , with an additional 2 years of follow-up . RESULTS The median follow-up time for all 1,236 eligible and assessable patients was 35.7 months . Stage , grade , histologic subtype , and percentage of patients receiving adjuvant therapy were similarly distributed between the groups . The median age at diagnosis for the 618 patients r and omly assigned to ERT was 57 years ( range , 26 to 91 years ) . Two hundred fifty-one patients ( 41.1 % ) were compliant with ERT for the entire treatment period . Disease recurrence was experienced in 14 patients ( 2.3 % ) . Eight patients ( 1.3 % ) developed a new malignancy . There were 26 deaths ( 4.2 % ) , and five deaths ( 0.8 % ) were a result of endometrial cancer . The median age at diagnosis for the 618 patients in the placebo group was 57 years ( range , 30 to 88 years ) . Twelve patients ( 1.9 % ) experienced disease recurrence . Ten patients ( 1.6 % ) developed a new malignancy . There were 9 deaths ( 3.1 % ) in the placebo group , and four deaths ( 0.6 % ) were a result of endometrial cancer . CONCLUSION Although this incomplete study can not conclusively refute or support the safety of exogenous estrogen with regard to risk of endometrial recurrence , it is noteworthy that the absolute recurrence rate ( 2.1 % ) and the incidence of new malignancy were low", "BACKGROUND Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later . However , the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation ( the hormone-timing hypothesis ) has not been tested . METHODS A total of 643 healthy postmenopausal women were stratified according to time since menopause ( and were r and omly assigned to receive either oral 17β-estradiol ( 1 mg per day , plus progesterone [ 45 mg ] vaginal gel administered sequentially [ i.e. , once daily for 10 days of each 30-day cycle ] for women with a uterus ) or placebo ( plus sequential placebo vaginal gel for women with a uterus ) . The primary outcome was the rate of change in carotid-artery intima-media thickness ( CIMT ) , which was measured every 6 months . Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography ( CT ) , which was performed when participants completed the r and omly assigned regimen . RESULTS After a median of 5 years , the effect of estradiol , with or without progesterone , on CIMT progression differed between the early and late postmenopause strata ( P=0.007 for the interaction ) . Among women who were less than 6 years past menopause at the time of r and omization , the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group ( P=0.008 ) . Among women who were 10 or more years past menopause at the time of r and omization , the rates of CIMT progression in the placebo and estradiol groups were similar ( 0.0088 and 0.0100 mm per year , respectively ; P=0.29 ) . CT measures of coronary-artery calcium , total stenosis , and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum . CONCLUSIONS Oral estradiol therapy was associated with less progression of sub clinical atherosclerosis ( measured as CIMT ) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause . Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum . ( Funded by the National Institute on Aging , National Institutes of Health ; ELITE Clinical Trials.gov number , NCT00114517 . )", "Background —Although effects of statins on cardiovascular outcomes are well established in men , fewer data exist for women . Furthermore , the effects of statins plus hormone replacement therapy ( HRT ) on cardiovascular outcomes are uncertain . Methods and Results —We examined statin use , cardiovascular events , and total mortality in the Heart and Estrogen/progestin Replacement Study ( HERS ) , a r and omized clinical trial of estrogen plus progestin versus placebo in postmenopausal women with heart disease ( n=2763 ) . A nonr and omized comparison of statin users and nonusers revealed lower rates of the primary outcome , nonfatal myocardial infa rct ion or coronary heart disease death ( relative hazard [RH]=0.79 , 95 % confidence intervals [ CI ] 0.63 to 0.99 , P = 0.04 ) , and total mortality ( RH=0.67 , 95 % CI 0.51 to 0.87 , P = 0.003 ) . Rates of venous thromboembolic events were also lower among statin users ( RH=0.45 , 95 % CI 0.23 to 0.88 , P = 0.02 ) . HRT result ed in a significant increase in early risk for primary events in women who did not use statins ( RH=1.75 , 95 % CI 1.02 to 3.03 , P = 0.04 ) but not in statin users ( RH=1.34 , 95 % CI 0.63 to 2.86 , P = 0.45 ) . Adjustment for postr and omization statin use showed no effect of HRT on risk for the primary outcome ( RH=0.96 , 95 % CI 0.77 to 1.29;P = 0.72 ) . Conclusions —In HERS , statin use was associated with lower rates of cardiovascular events , venous thromboembolic events , and total mortality . These data provide strong support for statin use in eligible women with coronary disease", "OBJECTIVE To evaluate the effects of menopause hormonal therapy on disease activity in women with systemic lupus erythematosus ( SLE ) . METHODS We conducted a double-blind , r and omized clinical trial involving 106 women with SLE who were in the menopausal transition or in early or late postmenopause . Patients received a continuous-sequential estrogen-progestogen regimen ( n = 52 ) or placebo ( n = 54 ) . Disease activity was assessed at baseline and at 1 , 2 , 3 , 6 , 9 , 12 , 15 , 18 , 21 , and 24 months , according to the SLE Disease Activity Index ( SLEDAI ) . The primary outcome measure was global disease activity , estimated by measuring the area under the SLEDAI curve . Secondary outcome measures included maximum SLEDAI score , change in SLEDAI score , incidence of lupus flares , median time to flare , medication use , and adverse events . Results were studied using intent-to-treat analysis . RESULTS At baseline , demographic and disease characteristics were similar in both groups . Mean + /- SD SLEDAI scores were 3.5 + /- 3.3 and 3.1 + /- 3.4 in the menopause hormonal therapy and placebo groups , respectively ( P = 0.57 ) . Disease activity remained mild and stable in both groups throughout the trial . There were no significant differences between the groups in global or maximum disease activity , incidence or probability of flares , or medication use . Median time to flare was 3 months in both groups . Thromboses occurred in 3 patients who received menopause hormonal therapy and in 1 patient who received placebo . One patient in each group died during the trial due to sepsis . CONCLUSION Menopause hormonal therapy did not alter disease activity during 2 years of treatment . However , an apparently increased risk of thrombosis seems to be a real threat in women with SLE who receive menopausal hormone therapy", "Context : The Women 's Health Initiative ( WHI ) r and omized controlled trial that compared estrogen plus progestin versus placebo was stopped because of a significantly increased risk of breast cancer in the active treatment group ( reason 1 ) , and because a global index supported a finding of overall harm ( reason 2 ) . The possibility that the findings could have been accounted for by bias was not considered . Objective : The present analysis was undertaken to determine whether detection bias is a plausible alternative to causality as an explanation for those findings that contributed to the reasons for discontinuing the study . Design , setting and participants : This work took the form of a sensitivity analysis of the published WHI data to determine the magnitude of the detection bias required to account for those findings that contributed to the two reasons for stopping the study . Main outcome measures : These were differences in incidence rates of breast cancer ( reason 1 ) , and breast cancer , coronary heart disease , stroke and pulmonary embolism ( reason 2 ) , among estrogen plus progestin and placebo recipients . Results In the WHI study , 44.4 % of the women on active treatment , as against 6.8 % of the placebo recipients , had their treatments unblinded ( mainly because of vaginal bleeding ) . Among them , detection bias could not be excluded . For the three cardiovascular outcomes , bias became a strong likelihood after the women were twice caution ed about possible increased risks observed in the interim data among estrogen plus progestin recipients . On the None hypothesis , bias could have accounted for the observed associations if , on average , it augmented the detection of disease that would otherwise have gone undiagnosed by 0.7 - 0.8/1000 per year . Conclusions : For differences in incidence of the order of 0.7 - 0.8/1000 per year , it is not possible to discriminate between causation and detection bias as alternative explanations for the findings", "The endothelium is thought to play an important role in the genesis of atherosclerosis , and several lines of evidence suggest that the effect of an intervention on endothelial function might predict its involvement in coronary disease progression and in the rate of cardiovascular events . Estrogen has direct effects on the blood vessel wall , indicating that vascular endothelium may play a key role in the cardiovascular protective effects of hormone replacement therapy ( HRT ) . Raloxifene relaxes coronary arteries in vitro by an estrogen receptor – dependent and NO-dependent mechanism , thus suggesting that this selective estrogen receptor modulator could also have beneficial effects on endothelial function . This study compared the effects of HRT and raloxifene on NO products , endothelin-1 plasma levels , and endothelium-dependent vasodilatation in postmenopausal women . Healthy postmenopausal women ( n=90 ) were enrolled in a double-blind , r and omized , placebo-controlled , 6-month trial . Women were r and omly assigned to receive continuous HRT ( 1 mg 17&bgr;-estradiol combined with 0.5 mg norethisterone acetate ) , raloxifene ( 60 mg/d ) , or placebo for 6 months . Flow-mediated endothelium-dependent vasodilation of the brachial artery , plasma NO concentrations , and endothelin levels were measured at baseline and after 6 months of therapy . The mean baseline level of NO breakdown products was 26.5±10.7 & mgr;mol/L and increased to 36.3±11.4 & mgr;mol/L after 6 months of treatment with raloxifene . The mean baseline plasma endothelin level was 17.3±8.9 pg/mL and decreased to 11.5±2.1 pg/mL after 6 months of treatment with the selective estrogen receptor modulator . The mean baseline ratio of NO ( breakdown products ) to endothelin was also significantly increased at the end of treatment with raloxifene . Postmenopausal women treated with HRT had similar changes in plasma nitrites/nitrates and endothelin levels as well as in the ratio of NO to endothelin . In contrast , these markers of endothelial function did not change in the placebo-treated women . Flow-mediated endothelium-dependent vasodilation of the brachial artery was 8.3±2.1 % at baseline and increased to 12.3±2.1 % after 6 months of treatment with raloxifene . HRT also caused a significant and similar increase in flow-mediated endothelium-dependent vasodilation . No change in flow-mediated vasodilation was observed in the participants treated with placebo . We conclude that raloxifene therapy and HRT influence endothelial function and improve flow-mediated endothelium-dependent vasodilation to a comparable extent in healthy postmenopausal women at least after a 6-month treatment period . However , further investigation is warranted to enhance our underst and ing of the mechanisms of the effect of raloxifene on vascular function and to determine whether its effect on endothelial function may contribute to the reduction in cardiovascular-related morbidity and mortality", "Background At the time of feasibility work and final design of the trial there was no r and omised control trial evidence for the long-term risks and benefits of hormone replacement therapy . Observational studies had suggested that long term use of estrogen was likely to be associated , amongst other things , with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer . Concomitant use of progestogens had been shown to protect against endometrial cancer , but there were few data showing how progestogen might affect estrogen actions on other conditions . Disease specific risks from observational studies suggested that , overall , long-term HRT was likely to be beneficial . Several studies showed that mortality from all causes was lower in HRT users than in non-users . Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women . The WISDOM trial was design ed to compare combined estrogen and progestogen versus placebo , and estrogen alone versus combined estrogen and progestogen . During the development of WISDOM the Women 's Health Initiative trial was design ed , funded and started in the US . Design R and omised , placebo , controlled , trial . Methods The trial was set in general practice s in the UK ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . In these practice s 284175 women aged 50–69 years were registered with 226282 potentially eligible . We sought to r and omise 22300 postmenopausal women aged 50 – 69 and treat for ten years . The interventions were : conjugated equine estrogens , 0.625 mg orally daily ; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily ; matched placebo . Primary outcome measures were : major cardiovascular disease , osteoporotic fractures , breast cancer and dementia . Secondary outcomes were : other cancers , all cause death , venous thromboembolism and cerebro-vascular disease . Results The trial was prematurely closed during recruitment following publication of early results from the Women 's Health Initiative . At the time of closure , 56583 had been screened , 8980 entered run-in , and 5694 ( 26 % of target of 22,300 ) r and omised . Those women r and omised had received a mean of one year of therapy , mean age was 62.8 years and total follow-up time was 6491 person years . Discussion The WISDOM experience leads to some simple messages . The larger a trial is the more simple it needs to be to ensure cost effective and timely delivery . When a trial is very costly and beyond the re sources of one country , funders and investigators should make every effort to develop international collaboration with joint funding", "BACKGROUND Observational studies have suggested that estrogen-replacement therapy may reduce a woman 's risk of stroke and death . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of estrogen therapy ( 1 mg of estradiol-17beta per day ) in 664 postmenopausal women ( mean age , 71 years ) who had recently had an ischemic stroke or transient ischemic attack . Women were recruited from 21 hospitals in the United States and were followed for the occurrence of stroke or death . RESULTS During a mean follow-up period of 2.8 years , there were 99 strokes or deaths among the women in the estradiol group , and 93 among those in the placebo group ( relative risk in the estradiol group , 1.1 ; 95 percent confidence interval , 0.8 to 1.4 ) . Estrogen therapy did not reduce the risk of death alone ( relative risk , 1.2 ; 95 percent confidence interval , 0.8 to 1.8 ) or the risk of nonfatal stroke ( relative risk , 1.0 ; 95 percent confidence interval , 0.7 to 1.4 ) . The women who were r and omly assigned to receive estrogen therapy had a higher risk of fatal stroke ( relative risk , 2.9 ; 95 percent confidence interval , 0.9 to 9.0 ) , and their nonfatal strokes were associated with slightly worse neurologic and functional deficits . CONCLUSIONS Estradiol does not reduce mortality orthe recurrence of stroke in postmenopausal women with cerebrovascular disease . This therapy should not be prescribed for the secondary prevention of cerebrovascular disease", "BACKGROUND Little is known about the impact of post-menopausal hormone therapy on remnant-like particle ( RLP ) concentrations and about the relationship between RLP concentration and angiographic progression of coronary artery disease and clinical events in women . METHODS RLP cholesterol and triglyceride levels were measured at baseline and 3 months after r and omization in 397 post-menopausal women enrolled in The Women 's Angiographic Vitamin & Estrogen ( WAVE ) trial . Correlates of baseline RLP levels and changes in levels with post-menopausal hormone therapy were determined with multiple linear regression . Coronary angiography was performed at baseline and after a mean of 2.9 years . Changes in minimal and average luminal diameter were modeled with multivariate linear regression , clinical outcomes ( non-fatal myocardial infa rct ion , stroke , or cardiovascular death ) with multiple logistic regression . RESULTS The mean subject age was 65 years , 66 % of subjects were white , 18 % of subjects smoked , most subjects were overweight or obese , and 35 % of subjects had diabetes mellitus . RLP cholesterol ( 0.277 + /- 0.254 mmol/L ) and triglyceride ( 0.386 + /- 0.552 mmol/L ) levels corresponded approximately to the 90th percentile in women in the Framingham study . RLP levels did not change significantly with hormone therapy . RLP levels at baseline , changes in RLP levels , and on treatment RLP levels did not relate to angiographic changes or clinical outcomes ( non-fatal myocardial infa rct ion , stroke , or cardiovascular death ) . CONCLUSIONS RLP levels were high among post-menopausal women enrolled in the WAVE study , were not affected by hormone therapy , and did not relate to angiographic progression of coronary artery disease or clinical outcomes", "OBJECTIVE To investigate treatment adherence and factors related to non-adherence in the Estonian postmenopausal hormone therapy ( EPHT ) trial . METHODS A total of 1823 postmenopausal women aged 50 - 64 years were recruited into the EPHT trial from 1999 to 2001 . They were r and omised into the blind group receiving continuous orally administered postmenopausal hormone therapy ( PHT ) or a placebo and to a non-blind group receiving open-label PHT or no drugs . A woman was classified as non-adherent , if she had stopped treatment for at least 6-month period in treatment arms or used PHT for at least 6-month period in the control group . Adherence was calculated by the Kaplan-Meier method , and factors affecting adherence were studied with Cox proportional hazard modelling . RESULTS The rate of adherent women declined approximately 50 % during the first year in all treatment arms . Less than 10 % of the control group women started taking prescribed PHT . Older women , with lower education , with only one birth , never used oral contraceptives ( OC ) , with lower physical activity or who were dissatisfied with the information received from the trial staff , were more likely to discontinue . In treatment arms , the two most often cited reasons for non-adherence were side-effects and woman 's loss of interest in participation . Control group women started PHT due to the menopausal symptoms or on doctor 's recommendation . CONCLUSIONS The adherence was similar to that found for PHT use in everyday life . Higher adherence was related to younger age , higher education , previous OC use , physical activity and satisfaction with received information", "Context In observational studies , postmenopausal hormone therapy has been associated with lower fasting glucose levels . No prospect i ve , controlled trial has evaluated the effect of postmenopausal hormone therapy on the development of diabetes mellitus . Contribution Among the 2029 women in the Heart and Estrogen/progestin Replacement Study who had coronary disease but no diabetes at baseline , 6.2 % of those receiving 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate and 9.5 % of those receiving placebo developed diabetes . Implication s Recommendations about combination postmenopausal hormone therapy should consider that for every 30 women treated for 4 years , therapy might prevent one case of diabetes . The Editors Several clinical studies have evaluated the effect of postmenopausal hormone therapy on glucose metabolism and have had disparate results . Results from r and omized , controlled trials performed primarily in women without diabetes have found decreased mean fasting glucose or insulin levels among those assigned to hormone therapy ( 1 - 5 ) or no difference between those assigned to hormones and those assigned to placebo ( 6 - 10 ) . Fewer clinical trials have evaluated the effect of postmenopausal hormones on fasting glucose and insulin levels among women with type 2 diabetes mellitus , but again , the results have been mixed ( 11 - 16 ) . Observational studies have more consistently found that postmenopausal women taking hormone therapy have lower fasting glucose or hemoglobin A1c levels than those not taking hormones ( 17 - 24 ) . In addition , some ( 25 , 26 ) but not all ( 24 , 27 ) observational studies have noted a decreased incidence of diabetes among users of postmenopausal hormone therapy . No r and omized , controlled trial has evaluated the long-term effect of hormone therapy on diabetes incidence . To determine the effect of hormone therapy on subsequent diabetes , we analyzed data from the Heart and Estrogen/progestin Replacement Study ( HERS ) , in which 2763 postmenopausal women with documented coronary heart disease ( CHD ) were r and omly assigned to daily estrogen plus progestin therapy or to placebo . We evaluated the effect of hormone therapy on fasting glucose levels and incident diabetes over 4 years of follow-up . Methods Study Setting , Participants , and Design The design , methods , baseline characteristics ( 28 ) , and main findings ( 29 ) of HERS have been published elsewhere . Briefly , HERS was a r and omized , double-blind , placebo-controlled trial performed to evaluate daily doses of 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate for the prevention of coronary events in postmenopausal women with established CHD . The trial enrolled 2763 women at 20 clinical centers in the United States between January 1993 and September 1994 and followed participants for a mean of 4.1 years . To be included in the trial , women had to be younger than 80 years of age and have CHD , as evidence d by previous myocardial infa rct ion , coronary artery bypass graft surgery , mechanical revascularization , or angiographic evidence of coronary stenosis . Women who reported a CHD event within 6 months of r and omization or who had used postmenopausal hormone therapy within 3 months of the initial screening were excluded . Those with serum triglyceride levels of 3.39 mmol/L or greater ( 300 mg/dL ) , fasting blood glucose levels of 16.5 mmol/L or greater ( 300 mg/dL ) , or uncontrolled hypertension ( systolic blood pres sure 200 mg Hg or diastolic blood pressure 105 mm Hg ) were also excluded . Computer-generated r and om numbers were used to specify the allocation sequence . Women were r and omly assigned to the two treatment groups by use of a tamper-proof blocked r and omization stratified by clinical center . Participants , investigators , and staff at the clinical centers ; Wyeth-Ayerst Research ; and those adjudicating study outcomes were blinded to medication assignment . Additional details about sample size calculations , r and omization , and blinding procedures have been published elsewhere ( 29 ) . For our analysis , women were classified as having diabetes at the baseline visit if they reported a physician diagnosis of diabetes , were taking diabetes medication , or had a fasting plasma glucose level of 6.9 mmol/L or greater ( 126 mg/dL ) . Women were classified as having impaired fasting glucose if they had a fasting glucose level of 6.0 to 6.9 mmol/L ( 110 to 125 mg/dL ) at baseline . The remaining women were considered to have normal glucose metabolism . Data Collection At baseline , participants completed a question naire to ascertain age , race or ethnicity , education , smoking habits ( current , former , or never ) , alcohol consumption ( drinks per week ) , and exercise or walking activity . Physical examination variables measured at baseline were body weight , height , waist and hip circumference , and systolic and diastolic blood pressure . At baseline , at year 1 , and at the end-of-trial visit , participants had fasting blood tests for levels of total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , and lipoprotein(a ) measured by the Lipoprotein Analytical Laboratory at Johns Hopkins Hospital , Baltimore , Maryl and . Fasting serum glucose level was measured at baseline , at year 1 , and at the end-of-trial visit . Venous blood was obtained in the morning after a 12-hour fast , and SmithKline Beecham Clinical Laboratory , Van Nuys , California , analyzed the sample s using the hexokinase enzymatic method . We determined coefficients of variation by using ChemTrac ( Medical Analysis Systems , Inc. , Camarillo , California ) control . The coefficient of variation for serum glucose level was 1.6 % at a mean value ( SD ) of 4.2 0.05 mmol/L ( 77 1.0 mg/dL ) and 1.1 % at a mean value ( SD ) of 14.6 0.16 mmol/L ( 266 3.0 mg/dL ) . Adherence to study medication was reassessed every 4 months , at each visit . Ascertainment of Outcomes Diabetes incidence was not a secondary end point of the main HERS trial , but blood glucose level was prespecified as a variable that may mediate the effects of hormone therapy on CHD outcomes . We defined incident cases of diabetes by the presence of a fasting glucose level of 6.9 mmol/L or greater ( 126 mg/dL ) at year 1 or at the end-of-trial visit , self-report of new diabetes or a complication directly related to diabetes , or initiation of hypoglycemic medication at any point during follow-up . Self-reported complications included diabetic neuropathy , diabetic retinopathy , diabetic foot ulcer , and diabetic renal disease . Hypoglycemia was considered a complication of diabetes if a participant taking an antidiabetic medication reported it to the study staff as an adverse event . Statistical Analysis To compare fasting glucose levels by treatment assignment at baseline , at year 1 , and at the end-of-trial visit , t-tests were used . In addition , mixed linear models for repeated measures were used to assess treatment effects on fasting glucose level measured at year 1 and at the end-of-trial visit . Since mean values changed little after the year 1 visit , treatment effects were modeled by using the interaction between treatment assignment and an indicator for follow-up compared with baseline . These analyses were repeated after stratification by baseline diabetes status ( diabetes , impaired fasting glucose , or normal glucose metabolism ) . We calculated the number needed to treat for benefit by taking the inverse of the absolute risk reduction of incident diabetes between the treatment groups . The effect of treatment assignment on incident diabetes was assessed by using Cox proportional-hazards models . Primary analyses used unadjusted intention-to-treat models ; in supplementary analyses , we adjusted first for age and then for a range of potential confounders selected a priori , including age ; ethnicity ; education ; current smoking ; alcohol use ; exercise ; body mass index ; waist circumference ; and baseline use of diuretics , -blockers , angiotensin-converting enzyme inhibitors , and statins . In addition to intention-to-treat analyses , we also performed as treated analyses to determine whether the observed effect of hormone therapy on glucose levels and incident diabetes was also seen among women who adhered to the study medication . In these analyses , follow-up was censored at the beginning of the first 2-week period in which participants did not adhere to medication . To minimize potential confounding , these analyses were adjusted for baseline variables that differed between adherent and nonadherent women . We hypothesized that certain characteristics ( body mass index , waist circumference , weight change , smoking , triglyceride level , high-density lipoprotein cholesterol level , hypertension , and certain cardiac medications ) may mediate the effect of hormone therapy on fasting glucose level and diabetes incidence . To test this theory , we added postr and omization values of one or more hypothesized mediators as covariates to Cox regression models for incident diabetes . All analyses were conducted by using SAS software , version 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) . A P value less than 0.05 was considered statistically significant . Role of the Funding Sources The funding sources had no role in the design or conduct of this analysis or in the decision to su bmi t the paper for publication . Results Characteristics of women enrolled in HERS did not differ substantially between the hormone therapy group and the placebo group ( Table 1 ) . At the baseline examination , 734 women ( 26.6 % ) were classified as diabetic based on self-report of diagnosis or medication use ( n = 640 [ 87.2 % ] ) or by a fasting serum glucose level of 6.9 mmol/L or greater ( 126 mg/dL ) ( n = 101 [ 13.8 % ] ) . Impaired fasting glucose ( fasting serum glucose level , 6.0 to 6.9 mmol/L [ 110 to 125 mg/dL ] ) was noted in 218 women ( 7.9 % ) , and 1811 women ( 65.5 % ) were classified as nondiabetic ( Table 2 ) . Women with diabetes had higher body mass index , waist circumference ,", "BACKGROUND Whether menopausal hormone therapy ( MHT ) protects against cardiovascular disease ( CVD ) remains unclear . OBJECTIVE To assess atherosclerosis progression and CVD risk factors after MHT initiated in early menopause . DESIGN R and omized , controlled trial . ( Clinical Trials.gov : NCT00154180 ) . SETTING Nine U.S. academic centers . PARTICIPANTS Healthy menopausal women aged 42 to 58 years between 6 and 36 months from last menses without prior CVD events who had a coronary artery calcium ( CAC ) score less than 50 Agatston units and had not received estrogen or lipid-lowering therapy for at least 90 days . INTERVENTION Oral conjugated equine estrogens ( o-CEE ) , 0.45 mg/d , or transdermal 17β-estradiol ( t-E2 ) , 50 mcg/d , each with 200 mg of oral progesterone for 12 days per month , or placebo for 48 months . MEASUREMENTS Primary end point was annual change in carotid artery intima-media thickness ( CIMT ) . Secondary end points included changes in markers of CVD risk . RESULTS Of 727 r and omly assigned women , 89.3 % had at least 1 follow-up CIMT and 79.8 % had CIMT at 48 months . Mean CIMT increases of 0.007 mm/y were similar across groups . The percentages of participants in whom CAC score increased did not differ significantly across groups . No changes in blood pressure were observed with o-CEE or t-E2 . Low- and high-density lipoprotein cholesterol levels improved and levels of C-reactive protein and sex hormone-binding globulin but not interleukin-6 increased with o-CEE . Insulin resistance decreased with t-E2 . Serious adverse events did not differ by treatment . LIMITATION Power to compare clinical events was insufficient . CONCLUSION Four years of early MHT did not affect progression of atherosclerosis despite improving some markers of CVD risk . PRIMARY FUNDING SOURCE Aurora Foundation", "Background The aim of the study was to determine the effect of postmenopausal hormone therapy on women 's symptom reporting and quality of life in a r and omized trial . Methods 1823 women participated in the Estonian Postmenopausal Hormone Therapy ( EPHT ) Trial between 1999 and 2004 . Women were r and omized to open-label continuous combined hormone therapy or no treatment , or to blind hormone therapy or placebo . The average follow-up period was 3.6 years . Prevalence of symptoms and quality of life according to EQ-5D were assessed by annually mailed question naires . Results In the hormone therapy arms , less women reported hot flushes ( OR 0.20 ; 95 % CI : 0.14–0.28 ) , sweating ( OR 0.56 ; 95 % CI : 0.44–0.72 ) , and sleeping problems ( OR 0.66 ; 95 % CI : 0.52–0.84 ) , but more women reported episodes of vaginal bleeding ( OR 19.65 ; 95 % CI : 12.15–31.79 ) . There was no difference between the trial arms in the prevalence of other symptoms over time . Quality of life did not depend on hormone therapy use . Conclusion Postmenopausal hormone therapy decreased vasomotor symptoms and sleeping problems , but increased episodes of vaginal bleeding , and had no effect on quality of life . Trial registration numberIS RCT", "BACKGROUND Mammographic density is an independent risk factor for breast cancer . Postmenopausal hormone use is associated with an increase in mammographic density , but the magnitude of the density increase is unknown . METHODS Baseline and 12-month mammograms were obtained for 571 ( 65 % ) of the 875 women , aged 45 - 64 years , who were enrolled in the Postmenopausal Estrogen/Progestin Interventions Trial and r and omly assigned to receive placebo , daily conjugated equine estrogens at 0.625 mg/day ( CEE ) , daily CEE and medroxyprogesterone acetate ( MPA ) at 10 mg/day on days 1 - 12 ( CEE+MPA-cyclic ) , daily CEE and MPA at 2.5 mg/day ( CEE+MPA-continuous ) , or daily CEE and micronized progesterone ( MP ) at 200 mg/day on days 1 - 12 ( CEE+MP ) . We analyzed digitized mammograms to determine the percentage of the left breast that was composed of dense tissue ( i.e. , mammographic percent density ) . Linear regression analysis was used to examine the effects of treatments on the change in mammographic percent density between baseline and 12 months , before and after adjustment for possible confounders . All statistical tests were two-sided . RESULTS The adjusted absolute mean changes in mammographic percent density over 12 months were 4.76 % ( 95 % confidence interval [ CI ] = 3.29 % to 6.23 % ) , 4.58 % ( 95 % CI = 3.19 % to 5.97 % ) , and 3.08 % ( 95 % CI = 1.65 % to 4.51 % ) for women in the CEE+MPA-cyclic , CEE+MPA-continuous , and CEE-MP groups , respectively . Each of those absolute mean changes was statistically significantly different from the adjusted absolute mean change in mammographic percent density for women in the placebo group , which was -0.07 % ( 95 % CI = -1.50 % to 1.38 % ) . CONCLUSION Greater mammographic density was associated with the use of estrogen/progestin combination therapy , regardless of how the progestin was given , but not with the use of estrogen only", "CONTEXT Different menopausal hormone therapies may have varied effects on specific cognitive functions . We previously reported that conjugated equine estrogens ( CEE ) with medroxyprogesterone acetate had a negative impact on verbal memory but tended to impact figural memory positively over time in older postmenopausal women . OBJECTIVE The objective of the study was to determine the effects of unopposed CEE on changes in domain-specific cognitive function and affect in older postmenopausal women with prior hysterectomy . DESIGN This was a r and omized , double blind , placebo-controlled clinical trial . SETTING The study was conducted at 14 of 40 Women 's Health Initiative ( WHI ) clinical centers . PARTICIPANTS Participants were 886 postmenopausal women with prior hysterectomy , aged 65 yr and older ( mean 74 yr ) , free of probable dementia , and enrolled in the WHI and WHI Memory Study ( WHIMS ) CEE-Alone trial for a mean of 3 yr and followed up for a mean of 2.70 yr . INTERVENTION Intervention was 0.625 mg of CEE daily or placebo . MAIN OUTCOME MEASURES Annual rates of change in specific cognitive functions and affect , adjusted for time since r and omization , were measured . RESULTS Compared with placebo , unopposed CEE was associated with lower spatial rotational ability ( P other cognitive functions and affect . CONCLUSIONS CEE did not improve cognitive functioning in postmenopausal women with prior hysterectomy . CEE was associated with lower spatial rotational performance after an average of 3 yr of treatment . Overall , CEE does not appear to have enduring effects on rates of domain-specific cognitive change in older postmenopausal women", "We examined whether estradiol and norethindrone hormone therapy ( HT ) prevented decline in delayed verbal recall in older women with normal to mildly impaired memory functioning . This was a 2-year , r and omized , double-blind , placebo-controlled trial of 142 women aged 61 - 87 , r and omly assigned to receive 1 mg 17-beta estradiol daily and 0.35 mg norethindrone 3 days/week or daily placebo for 2 years . The primary outcome was short-delay verbal recall of the California Verbal Learning Test ( CVLT ) . To look for differences in response to HT by baseline short-delay recall , we examined the primary outcome in participants grouped according to whether their baseline scores were below average for the age group or greater than or equal to this score and according to whether they met criteria for Mild Cognitive Impairment ( MCI ) or not . 133 women completed 1 year of the trial and 128 completed 2 years . Prespecified covariates in all repeated measures analyses of covariance ( RANCOVA ) included age , education , APOE epsilon4 , and prior HT use . RANCOVA showed no overall significant treatment effects at year 1 or year 2 . After testing for an interaction , which was significant ( p=0.02 ) , we found that women in the HT group who scored at or above the average showed significantly less decline than the placebo group in short-delay verbal recall after 1 year , p=0.007 and 2 years , p=0.01 . No treatment effects were found in women below the average in either year . When grouped according to whether the participant met criteria for MCI , the interaction between treatment group and MCI subgroup was not significant . These results suggest that benefits of estrogen exposure may be limited to those with average to above average scores on the delayed verbal recall . HT dose and formulation may have contributed to these beneficial outcomes . Replication is warranted before recommendations can be made in the clinical setting", "BACKGROUND Hormone replacement therapy ( HT ) is known to increase the risk of breast cancer in healthy women , but its effect on breast cancer risk in breast cancer survivors is less clear . The r and omized HABITS study , which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer , was stopped early due to suspicions of an increased risk of new breast cancer events following HT . We present results after extended follow-up . METHODS HABITS was a r and omized , non-placebo-controlled noninferiority trial that aim ed to be at a power of 80 % to detect a 36 % increase in the hazard ratio ( HR ) for a new breast cancer event following HT . Cox models were used to estimate relative risks of a breast cancer event , the maximum likelihood method was used to calculate 95 % confidence intervals ( CIs ) , and chi(2 ) tests were used to assess statistical significance , with all P values based on two-sided tests . The absolute risk of a new breast cancer event was estimated with the cumulative incidence function . Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone . RESULTS Of the 447 women r and omly assigned , 442 could be followed for a median of 4 years . Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event ( HR = 2.4 , 95 % CI = 1.3 to 4.2 ) . Cumulative incidences at 5 years were 22.2 % in the HT arm and 8.0 % in the control arm . By the end of follow-up , six women in the HT arm had died of breast cancer and six were alive with distant metastases . In the control arm , five women had died of breast cancer and four had metastatic breast cancer ( P = .51 , log-rank test ) . CONCLUSION After extended follow-up , there was a clinical ly and statistically significant increased risk of a new breast cancer event in survivors who took HT", "Objective To assess the long term risks and benefits of hormone replacement therapy ( combined hormone therapy versus placebo , and oestrogen alone versus combined hormone therapy ) . Design Multicentre , r and omised , placebo controlled , double blind trial . Setting General practice s in UK ( 384 ) , Australia ( 91 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 years at r and omisation . At early closure of the trial , 56 583 had been screened , 8980 entered run-in , and 5692 ( 26 % of target of 22 300 ) started treatment . Interventions Oestrogen only therapy ( conjugated equine oestrogens 0.625 mg orally daily ) or combined hormone therapy ( conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily ) . Ten years of treatment planned . Main outcome measures Primary outcomes : major cardiovascular disease , osteoporotic fractures , and breast cancer . Secondary outcomes : other cancers , death from all causes , venous thromboembolism , cerebrovascular disease , dementia , and quality of life . Results The trial was prematurely closed during recruitment , after a median follow-up of 11.9 months ( interquartile range 7.1 - 19.6 , total 6498 women years ) in those enrolled , after the publication of early results from the women 's health initiative study . The mean age of r and omised women was 62.8 ( SD 4.8 ) years . When combined hormone therapy ( n=2196 ) was compared with placebo ( n=2189 ) , there was a significant increase in the number of major cardiovascular events ( 7 v 0 , P=0.016 ) and venous thromboembolisms ( 22 v 3 , hazard ratio 7.36 ( 95 % CI 2.20 to 24.60 ) ) . There were no statistically significant differences in numbers of breast or other cancers ( 22 v 25 , hazard ratio 0.88 ( 0.49 to 1.56 ) ) , cerebrovascular events ( 14 v 19 , 0.73 ( 0.37 to 1.46 ) ) , fractures ( 40 v 58 , 0.69 ( 0.46 to 1.03 ) ) , and overall deaths ( 8 v 5 , 1.60 ( 0.52 to 4.89 ) ) . Comparison of combined hormone therapy ( n=815 ) versus oestrogen therapy ( n=826 ) outcomes revealed no significant differences . Conclusions Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause . The results are consistent with the findings of the women 's health initiative study and secondary prevention studies . Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause , when the effect may be different . Trial registration Current Controlled Trials IS RCT N", "BACKGROUND In recent r and omized trials , conjugated equine estrogens ( CEE ) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk . These trials did not address the role of unopposed estrogen for coronary protection . METHODS A total of 10 739 women aged 50 to 79 years at baseline ( mean age , 63.6 years ) who had previously undergone hysterectomy were r and omized to receive CEE , 0.625 mg/d , or placebo at 40 US clinical centers beginning in 1993 . The trial was terminated early after 6.8 years of follow-up ( planned duration , 8.5 years ) . This report includes final , central ly adjudicated results for the primary efficacy outcome ( myocardial infa rct ion or coronary death ) , secondary coronary outcomes , and subgroup analyses . RESULTS During the active intervention period , 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo ( hazard ratio , 0.95 ; nominal 95 % confidence interval , 0.79 - 1.16 ) . Among women aged 50 to 59 years at baseline , the hazard ratio for the primary outcome was 0.63 ( nominal 95 % confidence interval , 0.36 - 1.08 ) . In that age group , coronary revascularization was less frequent among women assigned to receive CEE ( hazard ratio , 0.55 ; nominal 95 % confidence interval , 0.35 - 0.86 ) , as were several composite outcomes , which included the primary outcome and coronary revascularization ( hazard ratio , 0.66 ; nominal 95 % confidence interval , 0.44 - 0.97 ) . CONCLUSIONS Conjugated equine estrogens provided no overall protection against myocardial infa rct ion or coronary death in generally healthy postmenopausal women during a 7-year period of use . There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline ", "BACKGROUND Estrogen replacement therapy ( ERT ) , which is mainly used to relieve climacteric symptoms , increases a woman 's risk for uterine endometrial cancer and epithelial ovarian cancer ( EOC ) . Estrogens are often combined with progestins in hormone replacement therapy ( HRT ) to reduce the risk of uterine endometrial cancer . Data on the association between HRT including progestins and EOC risk are limited . This nationwide case-control study examined EOC risk in relation to HRT regimens with sequentially added progestins ( HRTsp ) and continuously added progestins ( HRTcp ) . METHODS Between 1993 and 1995 , we enrolled 655 histologically verified incident case patients with EOC and 3899 r and omly selected population controls , all 50 - 74 years of age . Data on HRT use were collected through mailed question naires . Multivariate-adjusted odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) were estimated by the use of unconditional logistic regression . RESULTS Risks of EOC were elevated among ever users as compared with never users of both ERT ( OR = 1.43 , 95 % CI = 1.02 to 2.00 ) and HRTsp ( OR = 1.54 , 95 % CI = 1.15 to 2.05 ) ; risks were elevated for serous , mucinous , and endometrioid subtypes . For all EOC types combined , the greatest risk increases were seen with hormone use exceeding 10 years . Ever use of HRTcp was not associated with increased EOC risk relative to HRTcp never use ( OR = 1.02 , 95 % CI = 0.73 to 1.43 ) . The risk of EOC was elevated among HRTsp ever users as compared with HRTcp ever users ( OR = 1.78 , 95 % CI = 1.05 to 3.01 ) . ORs for EOC after ever use of low-potency estrogens were 1.18 ( 95 % CI = 0.89 to 1.55 ) for oral and 1.33 ( 95 % CI = 1.03 to 1.72 ) for vaginal applications , but no relationship was seen between EOC risk and duration of use . CONCLUSION Ever users of ERT and HRTsp but not HRTcp may be at increased risk of EOC", "CONTEXT The Women 's Health Initiative Memory Study ( WHIMS ) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older . The effect of estrogen-alone therapy , also evaluated in WHIMS , on cognition has not been established for this population . OBJECTIVES To determine whether conjugated equine estrogen ( CEE ) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate ( CEE plus MPA ) . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled ancillary study of the Women 's Health Initiative ( WHI ) , WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995 . Of 3200 eligible women free of probable dementia enrolled in the WHI , 2947 ( 92.1 % ) were enrolled in WHIMS . Analyses were conducted on the 2808 women ( 95.3 % ) with a baseline and at least 1 follow-up measure of global cognitive function before the trial 's termination on February 29 , 2004 . INTERVENTIONS Participants received 1 daily tablet containing either 0.625 mg of CEE ( n = 1387 ) or matching placebo ( n = 1421 ) . MAIN OUTCOME MEASURE Global cognitive function measured annually with the Modified Mini-Mental State Examination ( 3MSE ) . RESULTS During a mean follow-up of 5.4 years , mean ( SE ) 3MSE scores were 0.26 ( 0.13 ) units lower than among women assigned to CEE compared with placebo ( P = .04 ) . For pooled hormone therapy ( CEE combined with CEE plus MPA ) , the mean ( SE ) decrease was 0.21 ( 0.08 ; P = .006 ) . Removing women with dementia , mild cognitive impairment , or stroke from the analyses lessened these differences . The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline ( all P 3MSE scores ( > 2 SDs ) was estimated to be 1.47 ( 95 % confidence interval , 1.04 - 2.07 ) . CONCLUSION For women aged 65 years or older , hormone therapy had an adverse effect on cognition , which was greater among women with lower cognitive function at initiation of treatment", "The objective of this study was to examine the effects of estrogen-based hormone therapy ( HT ) on regional cerebral metabolism in postmenopausal women ( mean age = 58 , SD = 5 ) at risk for development of dementia . The prospect i ve clinical trial design included pre- and post-intervention neuroimaging of women r and omized to continue ( HT+ ) or discontinue ( HT− ) therapy following an average of 10 years of use . The primary outcome measure was change in brain metabolism during the subsequent two years , as assessed with fluorodeoxyglucose-18 positron emission tomography ( FDG-PET ) . Longitudinal FDG-PET data were available for 45 study completers . Results showed that women r and omized to continue HT experienced relative preservation of frontal and parietal cortical metabolism , compared with women r and omized to discontinue HT . Women who discontinued 17-β estradiol (17βE)-based HT , as well as women who continued conjugated equine estrogen (CEE)-based HT , exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical ( PCC ) area . Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins ( with either 17βE or CEE ) . Together , these findings suggest that among postmenopausal subjects at risk for developing dementia , regional cerebral cortical metabolism is relatively preserved for at least two years in women r and omized to continue HT , compared with women r and omized to discontinue HT . In addition , continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC , known to undergo the most significant decline in the earliest stages of Alzheimer 's disease . Trial Registration Clinical Trials.gov", "BACKGROUND Results of observational studies suggest that hormone replacement therapy ( HRT ) could reduce the risk of coronary heart disease ( CHD ) , but those of r and omised trials do not indicate a lower risk in women who use oestrogen plus progestagen . The aim of this study was to ascertain whether or not unopposed oestrogen reduces the risk of further cardiac events in postmenopausal women who survive a first myocardial infa rct ion . METHODS The study was a r and omised , blinded , placebo controlled , secondary prevention trial of postmenopausal women , age 50 - 69 years ( n=1017 ) who had survived a first myocardial infa rct ion . Individuals were recruited from 35 hospitals in Engl and and Wales . Women received either one tablet of oestradiol valerate ( 2 mg ; n=513 ) or placebo ( n=504 ) , daily for 2 years . Primary outcomes were reinfa rct ion or cardiac death , and all-cause mortality . Analyses were by intention-to-treat . Secondary outcomes were uterine bleeding , endometrial cancer , stroke or other embolic events , and fractures . FINDINGS Frequency of reinfa rct ion or cardiac death did not differ between treatment groups at 24 months ( rate ratio 0.99 , 95 % CI 0.70 - 1.41 , p=0.97 ) . Similarly , the reduction in all-cause mortality between those who took oestrogen and those on placebo was not significant ( 0.79 , 0.50 - 1.27 , p=0.34 ) . The relative risk of any death ( 0.56 , 0.23 - 1.33 ) and cardiac death ( 0.33 , 0.11 - 1.01 ) was lowest at 3 months post-recruitment . INTERPRETATION Oestradiol valerate does not reduce the overall risk of further cardiac events in postmenopausal women who have survived a myocardial infa rct ion", "CONTEXT The timing of initiation of hormone therapy may influence its effect on cardiovascular disease . OBJECTIVE To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began . DESIGN , SETTING , AND PARTICIPANTS Secondary analysis of the Women 's Health Initiative ( WHI ) r and omized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were r and omized to conjugated equine estrogens ( CEE ) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were r and omized to CEE plus medroxyprogesterone acetate ( CEE + MPA ) or placebo . Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998 . MAIN OUTCOME MEASURES Statistical test for trend of the effect of hormone therapy on coronary heart disease ( CHD ) and stroke across categories of age and years since menopause in the combined trials . RESULTS In the combined trials , there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [ corrected ] cases of CHD and 239 cases of stroke in the placebo group . For women with less than 10 years since menopause began , the hazard ratio ( HR ) for CHD was 0.76 ( 95 % confidence interval [ CI ] , 0.50 - 1.16 ) ; 10 to 19 years , 1.10 ( 95 % CI , 0.84 - 1.45 ) ; and 20 or more years , 1.28 ( 95 % CI , 1.03 - 1.58 ) ( P for trend = .02 ) . The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years ; for women 10 to 19 years since menopause began , 4 per 10,000 person-years ; and for women 20 or more years from menopause onset , 17 per 10,000 person-years . For the age group of 50 to 59 years , the HR for CHD was 0.93 ( 95 % CI , 0.65 - 1.33 ) and the absolute excess risk was -2 per 10,000 person-years ; 60 to 69 years , 0.98 ( 95 % CI , 0.79 - 1.21 ) and -1 per 10,000 person-years ; and 70 to 79 years , 1.26 ( 95 % CI , 1.00 - 1.59 ) and 19 per 10,000 person-years ( P for trend = .16 ) . Hormone therapy increased the risk of stroke ( HR , 1.32 ; 95 % CI , 1.12 - 1.56 ) . Risk did not vary significantly by age or time since menopause . There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women ( HR of 0.70 for 50 - 59 years ; 1.05 for 60 - 69 years , and 1.14 for 70 - 79 years ; P for trend = .06 ) . CONCLUSIONS Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause , but this trend test did not meet our criterion for statistical significance . A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause . These data should be considered in regard to the short-term treatment of menopausal symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "Objective To investigate the long term effect of hormone replacement therapy on cardiovascular outcomes in recently postmenopausal women . Design Open label , r and omised controlled trial . Setting Denmark , 1990 - 93 . Participants 1006 healthy women aged 45 - 58 who were recently postmenopausal or had perimenopausal symptoms in combination with recorded postmenopausal serum follicle stimulating hormone values . 502 women were r and omly allocated to receive hormone replacement therapy and 504 to receive no treatment ( control ) . Women who had undergone hysterectomy were included if they were aged 45 - 52 and had recorded values for postmenopausal serum follicle stimulating hormone . Interventions In the treatment group , women with an intact uterus were treated with triphasic estradiol and norethisterone acetate and women who had undergone hysterectomy received 2 mg estradiol a day . Intervention was stopped after about 11 years owing to adverse reports from other trials , but participants were followed for death , cardiovascular disease , and cancer for up to 16 years . Sensitivity analyses were carried out on women who took more than 80 % of the prescribed treatment for five years . Main outcome measure The primary endpoint was a composite of death , admission to hospital for heart failure , and myocardial infa rct ion . Results At inclusion the women on average were aged 50 and had been postmenopausal for seven months . After 10 years of intervention , 16 women in the treatment group experienced the primary composite endpoint compared with 33 in the control group ( hazard ratio 0.48 , 95 % confidence interval 0.26 to 0.87 ; P=0.015 ) and 15 died compared with 26 ( 0.57 , 0.30 to 1.08 ; P=0.084 ) . The reduction in cardiovascular events was not associated with an increase in any cancer ( 36 in treated group v 39 in control group , 0.92 , 0.58 to 1.45 ; P=0.71 ) or in breast cancer ( 10 in treated group v 17 in control group , 0.58 , 0.27 to 1.27 ; P=0.17 ) . The hazard ratio for deep vein thrombosis ( 2 in treated group v 1 in control group ) was 2.01 ( 0.18 to 22.16 ) and for stroke ( 11 in treated group v 14 in control group ) was 0.77 ( 0.35 to 1.70 ) . After 16 years the reduction in the primary composite outcome was still present and not associated with an increase in any cancer . Conclusions After 10 years of r and omised treatment , women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality , heart failure , or myocardial infa rct ion , without any apparent increase in risk of cancer , venous thromboembolism , or stroke . Trial registration Clinical Trials.gov NCT00252408", "CONTEXT Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions , particularly memory . OBJECTIVE The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women . DESIGN This study was a r and omized , double-blind , placebo-controlled clinical trial . SETTING Participants were women from 14 of 40 clinical centers of the Women 's Health Initiative ( WHI ) . PARTICIPANTS Postmenopausal women ( 1416 ) aged 65 yr and older , free of probable dementia , and enrolled in WHI and the WHI Memory Study ( WHIMS ) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr , were studied . INTERVENTION Intervention was conjugated equine estrogen ( CEE ; 0.625 mg ) with 2.5 mg medroxyprogesterone acetate ( MPA ) in one daily tablet ( CEE + MPA ) or placebo . MAIN OUTCOME MEASURES Annual rates of change in specific cognitive functions and affect , adjusted for time since r and omization , were measured . RESULTS CEE + MPA had a negative impact on verbal memory ( P figural memory ( P = 0.012 ) over time compared with placebo , but other cognitive domains were not affected . Both effects on memory were evident only after long-term therapy . CEE + MPA did not significantly influence positive affect , negative affect , or depressive symptoms . CONCLUSIONS The effect of CEE + MPA on cognitive function varies across cognitive domains in older women , reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain . Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research", "Objective —The Heart and Estrogen/Progestin Replacement Study ( HERS ) found no overall effect of estrogen plus progestin ( compared with placebo ) on coronary event rates in 2763 postmenopausal women with established coronary disease ( mean 4.1 years of follow-up ) . In addition to the events trial , a carotid ultrasound sub study was established in 1993 to be conducted concurrently to determine whether hormone therapy affects the progression of the underlying atherosclerotic process . Methods and Results —Within the larger HERS , a subset of 362 participants underwent carotid B-mode ultrasound examinations at baseline and the end of follow-up . Progression of carotid atherosclerosis was measured as the temporal change in intimal-medial thickness ( IMT ) . Conclusions —IMT progressed in the hormone treatment and placebo groups , although there was no statistical difference between the rates : IMT progressed 26 & mgr;m/y ( 95 % CI 18 to 34 & mgr;m/y ) in the hormone group and 31 & mgr;m/y ( 95 % CI 21 to 40 & mgr;m/y ) in the placebo group ( P = 0.44 ) . There were also no significant treatment effects when the results were examined by carotid segment or were adjusted for covariates . These data support the American Heart Association recommendation that women with established coronary disease should not initiate hormone therapy with an expectation of atherosclerotic benefit", "BACKGROUND The Heart and Estrogen/Progestin Replacement Study ( HERS ) is the first large clinical trial design ed to test the efficacy of postmenopausal estrogen/progestin therapy for secondary prevention of coronary heart disease ( CHD ) . To examine the representativeness of the HERS cohort to the general population of postmenopausal women with CHD , we compared the baseline cardiovascular risk factor data from HERS with similar data from women presumed to have CHD from the National Health and Nutrition Examination Survey ( NHANES ) III . METHODS Age , race , and cardiovascular disease risk factors were compared in the 2763 postmenopausal women younger than 80 years old , with a uterus , and with documented CHD in HERS versus 145 similarly aged women with clinical or electrocardiographic evidence of CHD from phase I of NHANES III . RESULTS There were fewer current smokers in HERS ( 13 % ) than in the NHANES cohort ( 21.7 % , p = 0.05 ) . Similarly , a history of hypertension was less prevalent in HERS ( 58.6 % ) than in the NHANES cohort ( 69.3 % , p = 0.03 ) . Women with fasting triglyceride levels > 3.39 mmol/L or fasting glucose levels > 16.6 mmol/L were excluded from HERS , result ing in fewer diabetics ( 22.9 % vs 29.5 % , p = 0.26 ) and lower serum triglyceride levels ( 1.88 mmol/L vs 2.25 mmol/L , p = 0.19 ) in HERS versus the NHANES cohort . Systolic and diastolic blood pressure , body mass index , physical activity , and total LDL and HDL cholesterol were not significantly different between the two groups . CONCLUSIONS The HERS cohort had fewer CHD risk factors than women with myocardial infa rct ion or angina in NHANES III , although comparison is hindered by differences in selection criteria . The many women with diabetes and hypertriglyceridemia in the NHANES cohort emphasizes the importance of testing strategies for secondary prevention of CHD in this high-risk subgroup", "CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD", "The National Institutes of Health ( NIH ) has instructed participants in the estrogen-alone study of the Women ’s Health Initiative ( WHI ) , a large multi-center trial , to stop taking their study pills and to begin the follow-up phase of the study . Letters have been sent to all participants in the estrogenalone study , 11,000 healthy postmenopausal women who have had a hysterectomy , informing them of a recent NIH review of the study data . After careful consideration of the data , NIH has concluded that with an average of nearly 7 years of follow-up completed , estrogen alone does not appear to affect ( either increase or decrease ) heart disease , a key question of the study . At the same time , estrogen alone appears to increase the risk of stroke and decrease the risk of hip fracture . It has not increased the risk of breast cancer during the time period of the study . The increased risk of stroke in the estrogen-alone study is similar to what was found in the WHI study of estrogen plus progestin when that trial was stopped in July 2002 . In that study , women taking estrogen plus progestin had 8 more strokes per year for every 10,000 women than those taking the placebo . The NIH believes that an increased risk of stroke is not acceptable in healthy women in a research study . This is especially true if estrogen alone does not affect ( either increase or decrease ) heart disease , as appears to be the case in the current study . The NIH has determined that the results would not likely change if the estrogen trial continued to its planned completion in 2005 . Furthermore , enough data have been obtained to assess the overall risks and benefits of the use of estrogen in this trial . WHI research ers have begun a detailed analysis of the data from the estrogen-alone study and expect to report full results in the next two months . The report , to be published in a peer- review ed journal , will include additional data collected through the end of February 2004 . A separate report will contain information on probable dementia or mild cognitive impairment in the women age 65 and older who participated in the estrogen-alone WHI-Memory Study ( WHIMS ) , an ancillary study of the WHI Hormone Trials . Preliminary data suggest that for the WHIMS participants who were on estrogen alone when compared to the women who were taking the placebo , there was a trend toward increased risk of probable dementia and /or mild cognitive impairment . The WHI estrogen study was design ed to assess the effect of long-term use of hormone therapy in healthy postmenopausal women on the prevention of heart disease and hip fractures , and any associated change in risk for breast cancer . It was not design ed to evaluate the short-term risks and benefits of hormones for the treatment of moderate to severe menopausal symptoms . The estrogen-alone study involved women ages 50 to 79 years . Study participants were r and omly assigned to a daily dose of estrogen—0.625 mg/day of conjugated equine estrogen — or a placebo . The NIH decision to stop the estrogen-alone trial was made on February 2 , 2004 . In November and December 2003 , the WHI Data and Safety Monitoring Board ( DSMB ) , an independent advisory committee which regularly review s study data and oversees the safety of study participants , review ed the latest data from the estrogen-alone study . The DSMB was split as to whether the study pills should be stopped or whether the pills should be continued , provided that a letter would be sent to the participants clearly informing them of the stroke risks and other findings . After careful review , the NIH decided that women in the estrogen-alone study should stop taking their study pills . From the National Heart , Lung , and Blood Institute of the National Institutes of Health", "BACKGROUND In the post-intervention period of the Women 's Health Initiative ( WHI ) trial , women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo . Results also suggested that the combined hormone therapy might increase mortality from lung cancer . To assess whether such an association exists , we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period . METHODS The WHI study was a r and omised , double-blind , placebo-controlled trial undertaken in 40 centres in the USA . 16 608 postmenopausal women aged 50 - 79 years with an intact uterus were r and omly assigned by a computerised , stratified , permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate ( n=8506 ) or matching placebo ( n=8102 ) . We assessed incidence and mortality rates for all lung cancer , small-cell lung cancer , and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00000611 . FINDINGS After a mean of 5.6 years ( SD 1.3 ) of treatment and 2.4 years ( 0.4 ) of additional follow-up , 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group ( incidence per year 0.16%vs 0.13 % ; hazard ratio [ HR ] 1.23 , 95 % CI 0.92 - 1.63 , p=0.16 ) . 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo ( 0.14%vs 0.11 % ; HR 1.28 , 0.94 - 1.73 , p=0.12 ) . More women died from lung cancer in the combined hormone therapy group than in the placebo group ( 73 vs 40 deaths ; 0.11%vs 0.06 % ; HR 1.71 , 1.16 - 2.52 , p=0.01 ) , mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group ( 62 vs 31 deaths ; 0.09%vs 0.05 % ; HR 1.87 , 1.22 - 2.88 , p=0.004 ) . Incidence and mortality rates of small-cell lung cancer were similar between groups . INTERPRETATION Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer , it increased the number of deaths from lung cancer , in particular deaths from non-small-cell lung cancer . These findings should be incorporated into risk-benefit discussion s with women considering combined hormone therapy , especially those with a high risk of lung cancer . FUNDING National Heart , Lung and Blood Institute , National Institutes of Health", "The Women 's Health Initiative Study of Cognitive Aging ( WHISCA ) was a two armed , r and omized , placebo controlled , clinical trial design ed to assess the efficacy of postmenopausal hormone therapy on age related changes in specific cognitive functions . WHISCA was an ancillary study to the Women 's Health Initiative ( WHI ) and the WHI Memory Study ( WHIMS ) and enrolled 2302 women aged 66 to 84 years ( mean 73.9 ; st and ard deviation 3.8 ) who did not meet criteria for dementia . Women were r and omly assigned by the WHI to hormone treatment ( unopposed conjugated estrogens ( CEE ) 0.625 mg/day if they were without a uterus ; CEE combined with medroxyprogesterone acetate ( MPA ) 2.5 mg/day otherwise ) or placebo for an average of three years before the first WHISCA assessment . WHISCA investigated the effects of hormone therapy on rates of change over time in memory , other aspects of cognition ( language , attention , spatial ability ) , motor function , and mood . In this paper , we present the study rationale and design , including specific cognitive measures , and the challenges of incorporating WHISCA into an ongoing r and omized trial . WHISCA provided a unique opportunity to investigate the potential of hormone therapy to modify age related changes in specific cognitive functions . WHISCA also demonstrated the feasibility of adding a detailed cognitive assessment into an ongoing clinical trial to address an important issue in women 's health , despite the challenges of maintaining the integrity of the parent studies , ensuring high retention , and achieving high quality assurance across sites", "Sixty-one postmenopausal women were r and omized into 3 groups . Two groups of women were treated with estrogen replacement therapy ( ERT ) by percutaneous administration of estradiol gel at a dosage of 1.25 g and 2.5 g , respectively . The third group of women , receiving no treatment except placebo , was studied concurrently as a control group . Bone mineral density ( BMD ) was measured by quantitative computed tomography ( QCT ) in the vertebrae from T12-L3 and hormones ( E1 , E2 , FSH , LH and testosterone ) were determined by radioimmunoassay at baseline , then at 6 monthly intervals thereafter . One year of the study has been completed thus far . The results of this study indicate that : ( 1 ) loss of BMD in the control group was observed significantly only in surgical menopausal women and no significant loss of BMD was observed in women receiving ERT treatment regimens ; ( 2 ) decrease of E1 in control group and increase of E1 in the treatment group were both significant . These data suggest that percutaneous ERT may be used in prevention of postmenopausal bone loss , particularly in surgical menopausal women and the increased E1 may play a beneficial role in inhibiting loss of bone mass and relieving menopausal syndrome . Different dosages of estradiol gel which did not create any significant difference between the 2 treatment groups , need a longer period of follow-up", "The Women 's Angiographic Vitamin and Estrogen trial was a r and omized , double-blind , placebo-controlled study design ed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease . Postmenopausal women with one or more angiographically documented coronary stenoses of 15 - 75 % at baseline were assigned in a 2 x 2 factorial r and omization to active hormone replacement therapy ( conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri ) or placebo and to active vitamins E and C or their placebos . Seven clinical centers , five in the United States and two in Canada , r and omized 423 women between July 1997 and July 1999 . Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years", "BACKGROUND Recent r and omized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease ( CHD ) . In this report , we provide the final results with regard to estrogen plus progestin and CHD from the Women 's Health Initiative ( WHI ) . METHODS The WHI included a r and omized primary -prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line . Participants were r and omly assigned to receive conjugated equine estrogens ( 0.625 mg per day ) plus medroxyprogesterone acetate ( 2.5 mg per day ) or placebo . The primary efficacy outcome of the trial was CHD ( nonfatal myocardial infa rct ion or death due to CHD ) . RESULTS After a mean follow-up of 5.2 years ( planned duration , 8.5 years ) , the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits . Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 ( nominal 95 percent confidence interval , 1.00 to 1.54 ; 95 percent confidence interval after adjustment for sequential monitoring , 0.97 to 1.60 ) . The elevation in risk was most apparent at one year ( hazard ratio , 1.81 [ 95 percent confidence interval , 1.09 to 3.01 ] ) . Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy , higher base-line levels of C-reactive protein , other biomarkers , and other clinical characteristics did not significantly modify the treatment-related risk of CHD . CONCLUSIONS Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women , especially during the first year after the initiation of hormone use . This treatment should not be prescribed for the prevention of cardiovascular disease", "Venous thromboembolism , including thrombosis of the deep veins of the legs and embolism to the pulmonary arteries , is a serious and potentially fatal event . Venous thromboembolism is uncommon in the general population , occurring in about 1 to 4 per 1000 adults annually ( 1 , 2 ) . However , the risk is increased in persons with previous venous thromboembolism ( 3 ) , recent surgical procedures ( 4 , 5 ) , immobilization , fracture of a lower extremity ( 4 , 6 , 7 ) , cancer ( 4 , 6 , 7 ) , and inherited coagulation disorders ( 8 , 9 ) . Use of oral contraceptive pills increases risk for venous thromboembolism ( 1 , 2 ) . This increased risk is thought to be due to estrogen and to be dose related ( 3 , 4 ) . The biological potency of the estrogens generally used in postmenopausal hormone therapy is about one-fourth to one-fifth that of the estrogens in modern oral contraceptives . Until recently , there has been little evidence that low-dose estrogen therapy is associated with increased risk for venous thromboembolism ( 5 - 8 ) . Recent observational studies have suggested that postmenopausal hormone therapy causes a twofold to fourfold increase in risk for idiopathic deep venous thrombosis and pulmonary embolism ( 9 - 13 ) . However , these findings may be biased if women taking estrogen are more likely to be evaluated for nonspecific symptoms suggestive of venous thromboembolism . The Heart and Estrogen/progestin Replacement Study ( HERS ) was a r and omized , blinded , placebo-controlled trial of the effect of daily conjugated equine estrogen , 0.625 mg , plus medroxyprogesterone acetate , 2.5 mg , on the rate of new coronary events in 2763 postmenopausal women with established coronary heart disease ( 14 ) . One of the specified secondary outcomes of this trial was venous thromboembolism . An increased risk for venous thromboembolism among women assigned to hormone therapy was noted by the HERS Data and Safety Monitoring Board . The Board instructed the HERS investigators to inform participants and the scientific community of this risk and to institute measures to reduce risk . At a mean follow-up of 3.3 years , the HERS investigators notified participants to discontinue study medication in situations associated with increased risk for venous thromboembolism , such as surgery , hospitalization , fracture , and cancer , and published a letter noting the increased risk ( 15 ) . This report presents the full analysis of the findings . Methods Participants in HERS were postmenopausal women younger than 80 years of age who had coronary disease ( myocardial infa rct ion , coronary artery bypass surgery , percutaneous coronary revascularization , or angiographic evidence of at least 50 % narrowing of one or more major coronary arteries ) and had not had a hysterectomy . Women were excluded if their coronary event occurred within 6 months of r and omization ; they had used hormone therapy within 3 months of r and omization ; they had a history or baseline findings suggestive of venous thromboembolism , breast cancer , or endometrial cancer ; or they had uncontrolled hypertension , diabetes , or other life-threatening diseases ( 16 ) . The protocol was approved by the institutional review board at each of the 20 HERS clinical centers , and all participants provided written informed consent . Participants were r and omly assigned to take one tablet daily of conjugated equine estrogen , 0.625 mg , plus medroxyprogesterone acetate , 2.5 mg , or placebo that was identical in appearance . R and omization was stratified by clinical center and performed in blocks of 4 . To prevent unblinding of clinical center staff , HERS participants reported breast discomfort and vaginal bleeding directly to gynecology staff , who were located separately from the clinical center staff , did not communicate with clinical center personnel about breast or gynecologic problems , and did not participate in ascertainment of outcomes . Follow-up visits to the clinical centers occurred at 4-month intervals . Coronary events ( nonfatal myocardial infa rct ion and coronary death ) were the primary outcome of the trial ( 14 ) . At each visit , clinic staff asked participants if they had been told by a physician that they had a blood clot in the legs or lungs . Women were also asked whether they had been hospitalized , and records were review ed to determine whether venous thromboembolism had occurred . Women were not routinely asked about symptoms of venous thrombosis , such as lower-extremity edema . Diagnosis of deep venous thrombosis required documentation of thrombosis of the popliteal or more proximal veins of the legs by venography , impedance plethysmography , or sonography . Pulmonary embolism required documentation by a nuclear lung scan that suggested a high probability of pulmonary embolism ( segmental or larger perfusion defect with ventilation mismatch ) or by pulmonary angiography that revealed a constant intraluminal filling defect on multiple films . Suspected venous thromboembolism was adjudicated independently and without knowledge of treatment assignment by two physicians at the HERS Coordinating Center , located at the University of California , San Francisco ; disagreements were resolved by consensus . Persons who analyzed data were also blinded to participants ' treatment status . Data were collected on events that occurred during the trial that might be predictors of venous thromboembolism , including fractures , nonfatal myocardial infa rct ion , congestive heart failure , stroke , and transient ischemic attack ( 16 ) . Venous thromboembolism was classified as idiopathic in women who did not have concomitant cancer , nonfatal myocardial infa rct ion , congestive heart failure , or stroke and did not have a fracture , inpatient surgery , or hospitalization in the 3 months before the venous thromboembolic event . In the primary analysis , an unadjusted Cox proportional-hazards model for time to first event was used to compare the rate of venous thromboembolism among women assigned to hormone therapy with the rate among women assigned to placebo . The primary analysis was intention-to-treat ; participants were categorized according to treatment assignment regardless of compliance . Participants who were lost to follow-up ( 33 women in the hormone therapy group and 36 in the placebo group ) were censored at the last date at which they were known to be alive without venous thromboembolism ; vital status was known for all women at the end of the trial . We also performed an as-treated analysis , in which inclusion in the risk sets was limited to women in both treatment groups whose average compliance with therapy during the trial ( measured by pill count ) was at least 80 % . Relative hazards were also estimated by year since r and omization ( women with events in earlier years were censored ) , and continuous trend in the log relative hazard was examined in a companion model . We repeated the main analyses separately for idiopathic and nonidiopathic venous thromboembolism . Potential risk factors for venous thromboembolism were first examined by using univariate proportional hazards models adjusted for treatment assignment . In these models , postr and omization events and medication use were represented by time-dependent indicators , which reverted to zero 90 days after fracture , surgery , or hospitalization or when therapy was discontinued . Variables associated with venous thromboembolism for which the associated P value was less than 0.2 in univariate analyses were considered for inclusion in multivariate models and retained in the model if the P value remained less than 0.2 . Statistical analyses were performed by using SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Results The 20 HERS centers enrolled 2763 women between February 1993 and September 1994 ; of these , 1380 were assigned to the hormone therapy group and 1383 to the placebo group . Participants ranged in age from 44 to 79 years ( mean age [ SD ] , 67 7 years ) . At baseline , the treatment groups did not differ significantly ( Table 1 ) . Table 1 . Baseline Characteristics of HERS Participants At the end of the first year , 82 % of women in the hormone therapy group and 91 % in the placebo group reported taking study medication ; by the end of the third year , these proportions had decreased to 75 % and 81 % , respectively . Cumulative incidence curves for all venous thromboembolic events ( deep venous thrombosis and pulmonary embolism ) are shown in the Figure . During 10 985 woman-years of follow-up , 47 women experienced a venous thromboembolic event : 34 in the hormone-treated group ( 6.2 per 1000 woman-years ) and 13 in the placebo group ( 2.3 per 1000 woman-years ) ( relative hazard , 2.7 [ 95 % CI , 1.4 to 5.0 ] [ P = 0.003 ] ; excess risk , 3.9 per 1000 woman-years [ CI , 1.4 to 6.4 per 1000 woman-years ] ; number needed to treat for harm , 256 [ CI , 157 to 692 ] ) . The relative hazard of venous thromboembolism did not differ significantly among the 20 clinical centers . Figure . Kaplan-Meier estimates of the cumulative incidence of venous thromboembolic events ( top ) , deep venous thrombosis ( middle ) , and pulmonary embolism ( bottom ) . More women in the hormone therapy group than in the placebo group experienced deep venous thrombosis ( 25 compared with 9 ; relative hazard , 2.8 [ CI , 1.3 to 6.0 ] ; P = 0.008 ) and pulmonary embolism ( 11 compared with 4 ; relative hazard , 2.8 [ CI , 0.9 to 8.7 ] ; P = 0.08 ) ( Table 2 ) . Two women , both in the hormone therapy group , died of pulmonary embolism . The relative hazard was increased for idiopathic ( relative hazard , 3.1 [ CI , 0.8 to 11.3 ] ) and nonidiopathic venous thromboembolic events ( relative hazard , 2.5 [ CI , 1.2 to 5.3 ] ) . The overall results were unchanged in an as-treated analysis that was limited to women who reported taking more than 80 % of their assigned study medication ( relative hazard , 3.2 [ CI , 1.5 to 6.9 ] ; P = 0.003 ) . Table 2 . Venous Thrombolic Events by Treatment Group and Year of R and omization Table 2 shows relative hazards for venous thromboembolism by year since r and omization . The number of episodes of pulmonary", "IMPORTANCE Postmenopausal hormone therapy with conjugated equine estrogens ( CEEs ) may adversely affect older women ’s cognitive function . It is not known whether this extends to younger women . OBJECTIVE To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function . DESIGN Trained , masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions . Cognitive testing was conducted an average of 7.2 years after the trials ended , when women had a mean age of 67.2 years , and repeated 1 year later . Enrollment occurred from 1996 through 1999 . SETTING Forty academic research centers . PARTICIPANTS The study population comprised 1326 postmenopausal women , who had begun treatment in 2 r and omized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years . INTERVENTION The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years . MAIN OUTCOMES AND MEASURES The primary outcome was global cognitive function . Secondary outcomes were verbal memory , attention , executive function , verbal fluency , and working memory . RESULTS Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo : mean ( 95 % CI ) intervention effect of 0.02 ( −0.08 to 0.12 ) st and ard deviation units ( P = .66 ) . Similarly , no overall differences were found for any individual cognitive domain ( all P > .15 ) . Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy : mean treatment effects of −0.17 ( −0.33 to −0.02 ) and −0.25 ( −0.42 to −0.08 ) , respectively ; however , this may be a chance finding . CONCLUSIONS AND RELEVANCE CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years . We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function , either in the short or longer term . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01124773", "Objective : The objective was to evaluate the effect of hormone replacement therapy ( HRT ) on plasma homocysteine levels in postmenopausal women with coronary artery disease ( CAD ) and to investigate associations of homocysteine to other cardiovascular risk factors . Methods : The women in this single-center , controlled , and r and omized study were examined at baseline , and after 3 and 12 months , after they had been recruited consecutively from patients referred for investigational coronary angiography . All analyses were performed examiner blind . They were r and omized to HRT consisting of transdermal application of continuous 17β-estradiol with cyclic medroxyprogesterone acetate ( MPA ) tablets for 14 days every 3rd month , or to a control group . Results : After 3 months of unopposed 17β-estradiol , no significant effect on homocysteine was observed compared to the control group . The absolute decrease of 5 % in median plasma homocysteine levels after 12-month HRT did not reach statistical significance . Plasma homocysteine seemed slightly higher in women with three- or four-vessel disease , but the difference was not significant . With increasing homocysteine levels , free tissue factor pathway inhibitor ( TFPI ) antigen increased , whereas E-selectin decreased . In women with diabetes or elevated blood glucose > 6.0 mmol/l , plasma homocysteine was correlated to body mass index , C-peptide and insulin as well as age . Conclusion : Transdermal application of 17β-estradiol and sequential MPA do not affect plasma homocysteine in women with established CAD . Plasma homocysteine is stable in women with CAD over time , and unless special intervention is undertaken , repetitive measurements are not necessary in this particular group of high-risk individuals . The circulating anticoagulant TEPI is related to plasma homocysteine", "OBJECTIVE To investigate the effect of pulsed estrogen therapy S21400 ( intranasal 17 beta-estradiol ) on different quality of life ( QoL ) dimensions in early postmenopausal women treated with S21400 150 microg per day , S21400 300 microg per day , or placebo in a double blind , r and omized , controlled 2-year study . STUDY DESIGN QoL was assessed based on the vali date d Women 's Health Question naire design ed for peri- and post-menopausal women . Three hundred and thirty-five healthy , early postmenopausal Danish women , 53 years of age in average , who completed one question naire at baseline and one under study treatment were included in the analysis set . All analyses were performed on an intention-to-treat basis . RESULTS QoL improved significantly in both S21400 groups compared to placebo in the dimensions ' memory/concentration ' , ' vasomotor symptoms ' , ' sleep problems ' and ' sexual behavior ' ( difference in mean change scores being respectively + 7.9 , + 28.3 , + 9.9 and + 10.8 % , p ' anxiety/depressed mood ' and ' well-being ' . CONCLUSION Pulsed estradiol therapy had a pronounced effect not only on vasomotor symptoms but also a significant and clinical ly relevant improvement in several other QoL dimensions ", "BACKGROUND Several small trials and many observational studies suggest that estrogen treatment in postmenopausal women improves cognition , but 2 large r and omized trials have shown harm . The effect of an ultra-low- dose of unopposed transdermal estradiol on cognition and health-related quality of life is unknown . OBJECTIVE To investigate the effect of unopposed ultra-low-dose transdermal estradiol on cognitive function and quality of life in postmenopausal women . DESIGN R and omized , placebo-controlled , double-blind trial with 2-year follow-up . The main outcome of the trial was change in bone density . Changes in cognitive function and quality of life were preplanned secondary outcomes of the trial . SETTING Nine clinical centers in the United States . PARTICIPANTS Postmenopausal women ( N = 417 ) , aged 60 to 80 years , with a normal bone density for age and an intact uterus . INTERVENTION A weekly transdermal patch that delivers estradiol , 0.014 mg/d ( n = 208 ) , or placebo ( n = 209 ) . MAIN OUTCOME MEASURES Seven st and ardized cognitive tests ( a total of 10 scores ) administered at baseline and years 1 and 2 to test global cognitive function , verbal and visuospatial memory , language , executive function , and semantic memory . The 36-Item Short-Form General Health Survey was administered to assess health-related quality of life in physical and mental domains . The sample size provided 80 % power to detect a st and ardized effect of 0.29 SD , a small-to-moderate difference . RESULTS Baseline characteristics were similar in the 2 treatment groups . At 2 years of follow-up , we found no statistically significant differences between treatment groups in change on any of the cognitive test scores or on the 36-Item Short-Form General Health Survey ( P > .12 for all ) . There was no consistent evidence that the effect of treatment on change in cognitive or 36-Item Short-Form General Health Survey scores depended on the level of baseline endogenous estradiol . CONCLUSION Postmenopausal treatment with ultra-low-dose unopposed transdermal estradiol for 2 years had no effect on change in cognitive function or in health-related quality of life over 2 years of treatment", "OBJECTIVE We sought to investigate the long-term effect of raloxifene and continuous combined hormone replacement therapy ( ccHRT ) on impedance to flow within the uterine artery in postmenopausal women . STUDY DESIGN A prospect i ve , r and omized , double-blind , placebo-controlled 2-year study was performed in 95 postmenopausal women . They received either 60 mg of raloxifene daily ( raloxifene 60 group ) , 150 mg of raloxifene daily ( raloxifene 150 group ) , ccHRT , or placebo . At baseline and thereafter every 6 months , color Doppler ultrasonography was used to measure the pulsatility index ( PI ) of the uterine artery . RESULTS After 24 months of treatment , compared with placebo , significant decreases were found in the PI in the raloxifene 150 group ( P = .021 ) and in the ccHRT group ( P = .007 ) . In the raloxifene 150 group compared with the placebo group , after 6 and 24 months , decreases were observed in median PI of -5 % and -15 % , respectively , and in the ccHRT group decreases of -2 % and -19 % , respectively , were found . CONCLUSION Long-term use of 150 mg of raloxifene daily or ccHRT reduces impedance to flow within the uterine artery . This indicates that high-dose raloxifene may exert cardiovascular protection", "OBJECTIVES At present the Women 's Health Initiative trial is the only reported r and omised controlled trial study ing the effects of hormone therapy among healthy postmenopausal women . The Women 's Health Initiative reports have been criticized for lacking in generalisability , due to the characteristics of the trial population . We aim ed to compare the health effects of oral continuous combined hormone therapy with a placebo and non-treatment among healthy Estonian women . METHODS Eligible women were r and omised into a blind group of hormone therapy versus placebo and into a non-blind group of open label hormone therapy versus non-treatment . One thous and seven hundred and seventy-eight postmenopausal women aged 50 - 64 at the time of sampling were recruited in 1999 - 2001 at three clinical centers in Estonia . Participants received conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5mg/d , or conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 5mg/d , if less than 3 years had passed since menopause at recruitment , or matched placebo or non-treatment . Trial treatment was stopped gradually from 1 January 2004 to 31 May 2004 . RESULTS After a follow-up period from 2.0 to 5.0 years the combined hazard ratio , stratified by blinding and adjusted for age at recruitment and former oral contraceptive use was 1.12 ( 95 % confidence interval [ CI ] : 0.90 - 1.40 ) for coronary heart disease , 1.24 ( 95 % CI : 0.85 - 1.82 ) for cerebrovascular disease , 1.36 ( 95 % CI : 0.73 - 2.52 ) for total cancer , and 0.61 ( 95 % CI : 0.42 to 0.89 ) for bone fractures . CONCLUSIONS The results from the Estonian Postmenopausal Hormone Therapy r and omised trial are consistent with the Women 's Health Initiative findings", "The Heart and Estrogen/progestin Replacement Study ( HERS ) is a r and omized , double-blind , placebo-controlled trial design ed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease ( CHD ) events in women . The participants are postmenopausal women with a uterus and with CHD as evidence d by prior myocardial infa rct ion , coronary artery bypass graft surgery , percutaneous transluminal coronary angioplasty , or other mechanical revascularization or at least 50 % occlusion of a major coronary artery . Between February 1993 and September 1994 , 20 HERS centers recruited and r and omized 2763 women . Participants ranged in age from 44 to 79 years , with a mean age of 66.7 ( SD 6.7 ) years . Most participants were white ( 89 % ) , married ( 57 % ) , and had completed high school or some college ( 80 % ) . As expected , the prevalence of coronary risk factors was high : 62 % were past or current smokers , 59 % had hypertension , 90 % had serum LDL-cholesterol of 100 mg/dL or higher , and 23 % had diabetes . Each woman was r and omly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo . Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events ( CHD death and nonfatal myocardial infa rct ion ) . We will also assess other major CHD endpoints , including revascularization and hospitalization for unstable angina . The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo . The trial was design ed to have power greater than 90 % to detect a 35 % reduction in the incidence of CHD events , assuming a 50 % lag in effect for 2 years and a 5 % annual event rate in the placebo group . The design , analysis , and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California , San Francisco . HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events", "CONTEXT Estrogen therapy is thought to promote gallstone formation and cholecystitis but most data derive from observational studies rather than r and omized trials . OBJECTIVE To determine the effect of estrogen therapy in healthy postmenopausal women on gallbladder disease outcomes . DESIGN , SETTING , AND PARTICIPANTS Two r and omized , double-blind , placebo-controlled trials conducted at 40 US clinical centers . The volunteer sample was 22,579 community-dwelling women aged 50 to 79 years without prior cholecystectomy . INTERVENTION Women with hysterectomy were r and omized to 0.625 mg/d of conjugated equine estrogens ( CEE ) or placebo ( n = 8376 ) . Women without hysterectomy were r and omized to estrogen plus progestin ( E + P ) , given as CEE plus 2.5 mg/d of medroxyprogesterone acetate ( n = 14,203 ) . MAIN OUTCOME MEASURES Participants reported hospitalizations for gallbladder diseases and gallbladder-related procedures , with events ascertained through medical record review . Cox proportional hazards regression was used to assess hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) using intention-to-treat and time-to-event methods . RESULTS The CEE and the E + P groups were similar to their respective placebo groups at baseline . The mean follow-up times were 7.1 years and 5.6 years for the CEE and the E + P trials , respectively . The annual incidence rate for any gallbladder event was 78 events per 10,000 person-years for the CEE group ( vs 47/10,000 person-years for placebo ) and 55 per 10,000 person-years for E + P ( vs 35/10,000 person-years for placebo ) . Both trials showed greater risk of any gallbladder disease or surgery with estrogen ( CEE : HR , 1.67 ; 95 % CI , 1.35 - 2.06 ; E + P : HR , 1.59 ; 95 % CI , 1.28 - 1.97 ) . Both trials indicated a higher risk for cholecystitis ( CEE : HR , 1.80 ; 95 % CI , 1.42 - 2.28 ; E + P : HR , 1.54 ; 95 % CI 1.22 - 1.94 ) ; and for cholelithiasis ( CEE : HR , 1.86 ; 95 % CI , 1.48 - 2.35 ; E + P : HR , 1.68 ; 95 % CI , 1.34 - 2.11 ) for estrogen users . Also , women undergoing estrogen therapy were more likely to receive cholecystectomy ( CEE : HR , 1.93 ; 95 % CI , 1.52 - 2.44 ; E + P : HR , 1.67 ; 95 % CI , 1.32 - 2.11 ) , but not other biliary tract surgery ( CEE : HR , 1.18 ; 95 % CI , 0.68 - 2.04 ; E + P : HR , 1.49 ; 95 % CI , 0.78 - 2.84 ) . CONCLUSIONS These data suggest an increase in risk of biliary tract disease among postmenopausal women using estrogen therapy . The morbidity and cost associated with these outcomes may need to be considered in decisions regarding the use of estrogen therapy", "Abstract The study was performed to compare the clinical effect of a hormone replacement therapy ( HRT ) with two different progestins . Postmenopausal women ( PMW ) with climacteric symptoms ( CS ) r and omly received for 12 months orally , either placebo ( n = 20 ) , 1 mg estradiol ( E ) plus 0.5 mg noretisterone acetate ( NETA ; n = 40 ) , or 2 mg drospirenone ( DRSP ; n = 40 ) , a testosterone- and spironolactone-derived molecule , respectively . Weight ( W ) declined only during E/DRSP ( p Fat mass ( FM ) decreased , similarly , during E/NETA and E/DRSP . Intracellular water ( ICW ) did not change , while extracellular water ( ECW ) decreased during E/DRSP ( p insulin resistance ( IR ) by the homeostatic model assessment for IR ( HOMA-IR ) ( p systolic ( p diastolic ( p did not change . In comparison to placebo CS , by the Kupperman Index ( KI ) , significantly declined ( p Menopause-specific Quality of Life ( MENQoL ) significantly declined versus placebo ( p body composition ( BC ) , where the addition of DRSP decreases ECW and body W ( BW )", "Prospect i ve studies of bone mass in women following oophorectomy for benign conditions were done by the double-blind technique . Skeletal response to treatment was measured by photon absorption densitometry . Untreated patients were found to lose bone mass rapidly during the first two years after oophorectomy . When estrogen replacement was started within two months of oophorectomy , it was found to be effective in preventing subsequent bone tissue loss . Three years following oophorectomy , untreated women who had already lost bone tissue , and who were then started on estrogen replacement , showed a highly significant increase in their bone mass . The women in whom this treatment was delayed for six years did not respond . No untoward effects were noted in these women , perhaps , in part , because they had undergone hysterectomy . Long-term effects of this treatment are now being evaluated", "OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth year ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo . Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved", "PURPOSE Our aim was to determine the effect of hormone replacement on physical performance measures , functional ability , physical activity , falls , and cognitive function in elderly women . SUBJECTS AND METHODS Following a 3-month , open-label , run-in phase , we r and omized 373 community-dwelling women aged 65 years and older to receive conjugated equine estrogen 0.625 mg/day plus or minus medroxyprogesterone 2.5 mg/day vs placebo for 3 years in a double-blind fashion . We assessed time to rise from a chair , timed walking , balance , Instrumental Activities of Daily Living , Physical Activity Scale of the Elderly , Folstein Mini-Mental State Examination , and falls . RESULTS Over 3 years , except for balance scores , performance measures declined significantly ( all P rising time ( 0.1 , -0.5 to 0.7 seconds [ mean , 95 % confidence interval ] ) , walking normal ( 0.0 , -0.4 to 0.4 seconds ) , and walking fast ( 0.2 , -0.1 to 0.6 seconds ) . There were no significant mean differences between the two groups for the Instrumental Activities of Daily Living ( 0.1 , -0.1 to 0.3 points ) , Physical Activity Scale of the Elderly ( -3 , -15 to 8 points ) , Folstein Mini-Mental State Examination ( -0.1 , -0.3 to 0.3 points ) , or the proportion of participants reporting falls ( -1 , -11 to 9 % ) . CONCLUSION In elderly women , hormone replacement had no statistically significant effect on cognition or balance , nor did it prevent the age-related decline in physical measures of mobility , ability to rise from a chair , self-reported activities of daily living , physical activity scores , or falls", "Background : Colorectal cancer incidence was reduced among women assigned to active treatment in the Women 's Health Initiative ( WHI ) estrogen plus progestin-r and omized trial , but the interpretation was obscured by an associated later stage of diagnosis . In contrast , the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis . Here , data from the WHI observational study are considered , in conjunction with colorectal cancer mortality data from the hormone therapy trials , in an attempt to clarify postmenopausal hormone therapy effects . Participants and Methods : Postmenopausal women ages 50 to 79 years at WHI enrollment . Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial , respectively . Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus . Colorectal cancers were verified by central medical and pathology report review . Results : Hazard ratios ( 95 % confidence intervals ) from the WHI observational study were 0.80 ( 0.53 - 1.20 ) for estrogen and 1.15 ( 0.74 - 1.79 ) for estrogen plus progestin , with , respectively , 168 and 175 women diagnosed with colorectal cancer . Delayed diagnosis with estrogen plus progestin is not evident in the observational study . No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period . Conclusion : Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinical ly important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up . ( Cancer Epidemiol Biomarkers Prev 2009;18(5):1531–7", "CONTEXT The Women 's Health Initiative Memory Study ( WHIMS ) previously found increased risk for dementia and no effect on mild cognitive impairment ( MCI ) in women treated with conjugated equine estrogens ( CEE ) plus medroxyprogesterone acetate ( MPA ) . OBJECTIVE To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled clinical trials of CEE ( estrogen-alone trial ) or CEE plus MPA ( estrogen plus progestin trial ) in community-dwelling women aged 65 to 79 years , conducted from June 1995 to July 8 , 2002 ( estrogen plus progestin ; n = 4532 ) , or to February 29 , 2004 ( estrogen-alone ; n = 2947 ) , in 39 of the 40 WHI clinical centers . INTERVENTIONS In the estrogen-alone trial , 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo ; in the estrogen plus progestin trial , 1 daily tablet containing CEE ( 0.625 mg/d ) plus MPA ( 2.5 mg/d ) vs matching placebos . MAIN OUTCOME MEASURES Probable dementia and MCI . RESULTS In the estrogen-alone trial , 47 participants were diagnosed with probable dementia , of whom 28 were assigned to CEE and 19 to placebo ( hazard ratio [ HR ] , 1.49 ; 95 % confidence interval [ CI ] , 0.83 - 2.66 ) . Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial ( 45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo , respectively ; P = .11 ) . When data were pooled per the original WHIMS protocol , the overall HR for probable dementia was 1.76 ( 95 % CI , 1.19 - 2.60 ; P = .005 ) . After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point , the HR was 1.77 ( 95 % CI , 0.74 - 4.23 ; P = .20 ) in the estrogen-alone trial and 2.19 ( 95 % CI , 1.25 - 3.84 ; P = .006 ) in the pooled trials . In the estrogen-alone trial , 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group ( HR , 1.34 ; 95 % CI , 0.95 - 1.89 ) . In the combined trial data , the HR was similar ( 1.25 ; 95 % CI , 0.97 - 1.60 ) . In the estrogen-alone trial , 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo ( HR , 1.38 ; 95 % CI , 1.01 - 1.89 ; P = .04 ) . CONCLUSIONS Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined . Pooling data for estrogen alone and estrogen plus progestin result ed in increased risks for both end points . Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended", "BACKGROUND The Women 's Health Initiative ( WHI ) clinical trial of conjugated equine estrogens ( CEEs ) , involving 10,739 postmenopausal women with hysterectomy , aged 50 to 79 years , was stopped early owing to lack of overall health benefit and increased risk of stroke . Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis , it is important to underst and the overall impact of this therapy on health-related quality of life ( HRQOL ) . METHODS All participants completed 6 specific measures of quality of life at baseline and 1 year , and a sub sample ( n = 1189 ) also completed the questions 3 years after r and omization . Changes in scores were analyzed for treatment effect . RESULTS R and omization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline ( mean benefit , 0.4 points on a 20-point scale ) and a statistically significant but small negative effect on social functioning ( mean effect , -1.3 points on a 100-point scale ) . There were no significant improvements due to CEE in the areas of general health , physical functioning , pain , vitality , role functioning , mental health , depressive symptoms , cognitive function , or sexual satisfaction at year 1 . A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes . Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline , CEE did not improve any of the HRQOL variables at year 1 . CONCLUSION In this trial of postmenopausal women with prior hysterectomy , oral CEE did not have a clinical ly meaningful effect on HRQOL", "OBJECTIVE This study was undertaken to assess whether estrogen therapy ( ET ) reduces the risk of cognitive decline in women with cerebrovascular disease . STUDY DESIGN We conducted a r and omized , double-blind trial of estradiol 17beta versus placebo for secondary stroke prevention in 664 postmenopausal women with a recent stroke or transient ischemic attack . The Mini-Mental State Examination ( MMSE ) and 5 domain measures were obtained at baseline and exit . RESULTS Among 461 women withdrawn alive without stroke , ET did not have a significant effect on cognitive measures after an average of 3 years ( relative risk of MMSE decline : 0.74 , 95 % CI , 0.49 - 1.13 ) . In women with normal MMSE at entry , estrogen was associated with less decline ( relative risk , 0.46 , 95 % CI , 0.24 - 0.87 ) . CONCLUSION In this study , estradiol did not have significant effects on cognitive measures . However , in women with normal function at baseline , there may be a benefit for ET in reducing the risk for cognitive decline", "Postmenopausal hormone therapy is widely used to prevent diseases . This is not , however , based on the kind of evidence that is normally required of a preventive drug therapy : it is based on intermediary outcomes of trials and non-experimental studies . Many reasons can be postulated for the fact that we know little of this old and widely used therapy . To remedy the current situation , we should encourage r and omised controlled trials , reveal the insufficiency of the current evidence , and challenge the drug industry 's biased influence", "Objective : To test the hypothesis that effects of estrogen-containing hormone therapy on cognitive abilities differ between postmenopausal women near to , and further from , menopause . Methods : In this r and omized , double-blind , placebo-controlled trial , healthy women within 6 years of menopause or 10 + years after menopause were r and omly assigned to oral 17β-estradiol 1 mg/d or placebo . Women with a uterus received cyclic micronized progesterone vaginal gel or placebo . The primary outcome assessed at 2.5 and 5 years , compared between treatment groups , was change in a st and ardized composite of neuropsychological test scores assessing verbal episodic memory . Secondary outcomes assessed executive functions and global cognition . Results : A total of 567 women were included in modified intention-to-treat analyses after a mean treatment duration of 57 months . For verbal memory , the mean estradiol minus placebo st and ardized difference in composite scores ( −0.06 , 95 % confidence interval −0.22 to 0.09 ) was not significant ( 2-tailed p = 0.33 ) . Differences were similar in early and late postmenopause groups ( 2-tailed interaction p = 0.88 ) . Interactions between postmenopause groups and differences between treatment groups were not significant for executive functions or global cognition . Conclusions : Estradiol initiated within 6 years of menopause does not affect verbal memory , executive functions , or global cognition differently than therapy begun 10 + years after menopause . Estradiol neither benefits nor harms these cognitive abilities regardless of time since menopause . Classification of evidence : This study provides Class I evidence that estradiol initiated within 6 years of menopause does not affect cognition at 2.5 years differently than estradiol initiated 10 + years after menopause", "Midlife vascular risk factors influence later cognitive decline and Alzheimer 's disease ( AD ) . The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk , such as high blood pressure ( BP ) , which independently contributes to cognitive dysfunction and AD . We describe the extent to which vascular risk factors relate to cognition in healthy , middle-aged , recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study ( KEEPS-Cog ) at baseline . KEEPS-Cog is a double-blind , r and omized , placebo-controlled , parallel group , clinical trial , investigating the efficacy of low-dose , transdermal 17β-estradiol and oral conjugated equine estrogen on cognition . All results are cross-sectional and represent baseline data only . Analyses confirm that the KEEPS-Cog cohort ( n = 571 ) was middle aged ( mean 52.7 years , range 42 - 59 years ) , healthy , and free of cognitive dysfunction . Higher systolic BP was weakly related to poorer performance in auditory working memory and attention ( p = 0.004 ; adjusted for multiple comparisons p = 0.10 ) . This relationship was not associated with endogenous hormone levels , and systolic BP was not related to any other cognitive domain . BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy , recently menopausal women . Lower BP early in menopause may affect cognitive domains known to be associated with AD", "Over the last 40 years , there has been increasing epidemiological evidence that post-menopausal treatment with sex steroids in physiological doses may reduce the relative risk of cardiovascular disease ( CVD ) . These findings have been supported by biological studies showing favourable changes in cardiovascular risk factors with estrogen supplementation . The impact of the so-called ' healthy user ' bias has been eagerly debated , and the results of the first and only r and omized long-term clinical trial of HRT for primary prevention have therefore been long awaited . The dramatic decision to halt the Women 's Health Initiative ( WHI ) study before completion came unexpectedly as the consequence of not only an increased risk of breast cancer but also increased occurrence of cardiovascular events with HRT . Due to the superior design of the study , the results from the WHI study have had an enormous impact on the clinical recommendations of HRT to post-menopausal women , concurrent with a degradation of evidence from observational studies . It is not very likely that other long-term r and omized clinical trials ( RCTs ) will be completed and epidemiology has certainly been disreputed-so is this ' time out ' for HRT studies", "The aim of this study was to evaluate the efficacy of pulsed estrogen therapy ( intranasal 17β-estradiol ) in the prevention of postmenopausal bone loss . A total of 386 women ( 40–65 years old ) , less than 5 years past menopause , were r and omized to intranasal placebo , 17β-estradiol 150 µg , or 300 µg daily for 2 years . Women with an intact uterus received micronised progesterone 200 mg per day , 14 days of each 28-day cycle . Women r and omised to placebo-treatment received placebo progesterone . The primary endpoints were changes in BMD at the spine ( L2–L4 ) and femoral neck . Secondary endpoints were changes in bone turnover markers : serum osteocalcin ( sOC ) as a marker of bone formation and urinary C-terminal telopeptides ( uCTX ) as a marker of bone resorption . BMD increased at all measured sites in women receiving active treatment in a dose-related manner , the difference compared to placebo being 5.2 % and 6.7 % at the spine , and 3.2 % and 4.7 % at the hip , respectively , with 150 μg and 300 μg ( P the spine and hip , respectively , was observed in women receiving placebo ( P risk factor for osteoporotic fracture , the difference between placebo and 150 μg or 300 µg was even higher at the spine ( 5.4 % and 7.4 % , respectively ) , and at the femoral neck ( 4.0 % and 5.2 % , respectively ) . Correspondingly , uCTX decreased from baseline by 39 % and 46 % , and sOC by 22 % and 27 % , in the 150 µg group and 300 µg group ( all P of bone turnover markers after 1 year and BMD after 2 years , emphasizing that bone markers can predict BMD response during hormonal treatment . Acceptability and general tolerance were good . This study demonstrates that pulsed estrogen therapy at the dose of 150 μg and 300-μg per day prevents bone loss in a dose-dependant manner at each site studied , and normalizes bone turnover markers to premenopausal levels", "The Estrogen Replacement and Atherosclerosis ( ERA ) trial is a three-arm , r and omized , placebo-controlled , double-blind trial to evaluate the effects of estrogen replacement therapy ( 0.625 mg/day oral conjugated estrogen ) with or without continuous low-dose progestin ( 2.5 mg oral medroxyprogesterone acetate/day ) versus placebo on progression of atherosclerosis . A total of 309 postmenopausal women at five sites underwent baseline coronary angiography and were r and omized . Participants will have repeat coronary angiography after an average of 3.25 years of treatment . The primary outcome of interest will be change in minimum diameter of the major epicardial segments , as assessed by quantitative coronary angiography . The primary aim is to test the hypothesis that either form of hormone therapy will slow the progression or induce regression of coronary atherosclerosis compared to placebo . The secondary aims are to assess the effects of the two treatments versus placebo on endothelial function ( measured using flow-mediated vasodilator responses ) , on several presumed mediators of estrogen 's effect on atherosclerosis ( i.e. , plasma lipids and lipoproteins , blood pressure , glucose metabolism , hemostatic factors , and antioxidant activity ) , on other factors that influence the development of coronary heart disease ( i.e. , diet , smoking status , exercise , weight , and health-related quality of life issues ) , and on clinical cardiovascular events . The ERA trial is the first angiographic endpoint clinical trial to examine the effects of postmenopausal hormone replacement on coronary atherosclerosis in women . It will provide an unparalleled opportunity to determine if either regimen of hormone therapy is effective in slowing the progress of angiographically defined coronary atherosclerosis . This study will complement other estrogen replacement trials , such as the PEPI , HERS , and Women 's Health Initiative studies , to provide a more comprehensive examination of the effects of estrogen replacement on cardiovascular risk factors , anatomic and functional manifestations of atherosclerosis , and risk for coronary heart disease in postmenopausal women . Control Clin Trials 2000;21:257 -", "Objective Although joint symptoms are commonly reported after menopause , observational studies examining exogenous estrogen ’s influence on joint symptoms provide mixed results . Against this background , estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women ’s Health Initiative r and omized , placebo-controlled , clinical trial . Methods A total of 10,739 postmenopausal women who have had a hysterectomy were r and omized to receive daily oral conjugated equine estrogens ( 0.625 mg/d ) or a matching placebo . The frequency and severity of joint pain and joint swelling were assessed by question naire in all participants at entry and on year 1 , and in a 9.9 % r and om sub sample ( n = 1,062 ) after years 3 and 6 . Logistic regression models were used to compare the frequency and severity of symptoms by r and omization group . Sensitivity analyses evaluated adherence influence on symptoms . Results At baseline , joint pain and joint swelling were closely comparable in the r and omization groups ( about 77 % with joint pain and 40 % with joint swelling ) . After 1 year , joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group ( 76.3 % vs 79.2 % , P = 0.001 ) , as was joint pain severity , and the difference in pain between r and omization groups persisted through year 3 . However , joint swelling frequency was higher in the estrogen-alone group ( 42.1 % vs 39.7 % , P = 0.02 ) . Adherence-adjusted analyses strengthen estrogen ’s association with reduced joint pain but attenuate estrogen ’s association with increased joint swelling . Conclusions The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain", "There is growing and consistent evidence that estrogen use in postmenopausal women is associated with a substantial reduction in the occurrence of cardiovascular disease . However , remarkably little is known about the biological mechanisms by which estrogen therapy may influence risk . Even less information is available on the cardiovascular effects of combined estrogen-progestin use . PEPI was not design ed to test whether estrogen and estrogen-progestin therapy is efficacious in the prevention of cardiovascular disease , as a much larger trial with clinical disease outcomes is needed to answer that question . However , PEPI will provide critical evidence regarding the potential effectiveness of the various estrogen and estrogen/progestin regimens ni altering risk factors for cardiovascular disease in women . Detailed information on factors such as adherence , side effects , and general patient acceptability will also be ascertained . The main results from PEPI will provide the scientific community with information on the basic actions of estrogen and estrogen/progestin therapy on four biological systems believed to be causally associated with cardiovascular disease occurrence . Further , since the trial is design ed to continue for 3 years , PEPI will be able to provide information on longer term as well as short-term effects on these systems . Finally , the results from PEPI should enable women and their physicians to select an optimal hormonal regimen , i.e. , one that is acceptable , safe , and provides the most beneficial and least deleterious changes in cardiovascular and other risk factors", "Historically , estrogen replacement therapy has been advocated in postmenopausal women with anticipated benefits of alleviating perimenopausal symptoms , slowing osteoporosis and preventing heart disease . While the first two effects are known , estrogen ’s role in the prevention of heart disease is unclear . Recommendations for postmenopausal estrogen replacement therapy for heart disease prevention are largely based on clinical , animal model , and tissue-culture studies demonstrating improvements in cardiovascular risk factors and experimental atherosclerosis and numerous observational studies showing fewer cardiovascular events among estrogen users than among non-users1 - 4 . However , definite conclusions regarding estrogen use for the prevention of heart disease can not be ascertained based on these data , due to study limitations and biases . Thus , r and omized clinical trials were needed to further clarify the role of postmenopausal estrogen replacement in the prevention of heart disease . The Heart and Estrogen/progestin Replacement Study ( HERS ) sought to establish the role of hormone replacement therapy for secondary prevention of coronary heart disease5 . But , contrary to expectations , 4.1 years of oral conjugated estrogen plus medroxyprogesterone acetate demonstrated no favorable effects over placebo in either primary ( non-fatal myocardial infa rct ion and coronary heart disease death ) or secondary outcomes . In fact , there was a statistically significant increase in coronary heart disease events in the treatment group compared to the placebo group during the first year . Various theories emerged as research ers attempted to underst and the HERS findings . Some wondered if medroxyprogesterone acetate decreased estrogen ’s favorable effects6 , while others suggested that other unrecognized effects , such as proinflammatory or prothrombotic effects , could be negating estrogen ’s favorable effects on the endothelium and lipids7", "Estrogen replacement therapy confers many beneficial effects to postmenopausal women , such as slowing the rate of bone loss and decreasing the risk of coronary artery disease . This multicenter , placebo-controlled study evaluated the lowest effective daily dose of estrone sulfate ( 0.3 , 0.625 , or 1.25 mg ) combined with 1000 mg elemental calcium supplementation for preventing bone loss in the immediate postmenopausal period . Spinal bone mineral density was measured using quantitative computed tomography . Compared with baseline , bone mineral density increased significantly ( P Estrone sulfate administration ( 0.625 and 1.25 mg ) produced significant changes in various lipid measurements at both the 6- and 12-month observation points . The prevalence rates for adverse events were comparable among the estrone sulfate groups and the placebo group . Estrone sulfate 0.625 mg daily , combined with 1000 mg elemental calcium supplementation , was the minimum effective dosage to prevent loss of spinal bone mineral density in postmenopausal women over a 12-month period", "OBJECTIVE : To estimate the effects of estrogen plus progestin ( E+P ) therapy on menopausal symptoms , vaginal bleeding , gynecologic surgery rates , and treatment-related adverse effects in postmenopausal women . METHODS : R and omized , double-blind , placebo-controlled trial of 16,608 postmenopausal women , ages 50–79 ( mean ± st and ard deviation 63.3 ± 7.1 ) years , with intact uterus , r and omized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate ( n = 8,506 ) or placebo ( n = 8,102 ) , and followed for a mean of 5.6 years . Change in symptoms and treatment-related effects were analyzed at year 1 in all participants . Bleeding and gynecologic surgery rates were analyzed through study close-out . RESULTS : Baseline symptoms did not differ between the treatment groups . More women assigned to E+P than placebo reported relief of hot flushes ( 85.7 % versus 57.7 % , respectively ; odds ratio 4.40 ; 95 % confidence interval 3.40–5.71 ) , night sweats ( 77.6 % versus 57.4 % ; 2.58 ; 2.04–3.26 ) , vaginal or genital dryness ( 74.1 % versus 54.6 % ; 2.40 ; 1.90–3.02 ) , joint pain or stiffness ( 47.1 % versus 38.4 % ; 1.43 ; 1.24–1.64 ) , and general aches or pains ( 49.3 % versus 43.7 % ; 1.25 ; 1.08–1.44 ) . Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness ( 9.3 % versus 2.4 % , respectively ; 4.26 ; 3.59–5.04 ) , vaginal or genital discharge ( 4.1 % versus 1.0 % ; 4.47 ; 3.44–5.81 ) , vaginal or genital irritation ( 4.2 % versus 2.8 % ; 1.52 ; 1.27–1.81 ) , and headaches ( 5.8 % versus 4.7 % ; 1.26 ; 1.08–1.46 ) than women on placebo . Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms . Vaginal bleeding was reported by 51 % of women on E+P and 5 % of women on placebo at 6 months ; most bleeding was reported as spotting . Gynecologic surgeries ( hysterectomy and dilation and curettage ) were performed more frequently in women assigned to E+P ( 3.1 % versus 2.5 % for hysterectomy , hazard ratio = 1.23 , P = .026 ; 5.4 % versus 2.4 % for dilation and curettage , hazard ratio = 2.23 , P vasomotor symptoms and vaginal or genital dryness , but contributed to treatment-related effects , such as bleeding , breast tenderness , and an increased likelihood of gynecologic surgery . LEVEL OF EVIDENCE :", "BACKGROUND Postmenopausal hormone therapy has been associated with a 2- to 3-fold increased risk of venous thromboembolism ( VT ) ( including deep vein thrombosis and pulmonary embolism ) in observational studies and secondary prevention clinical trials . Clinical trial data on the effects of estrogen alone on VT are limited . METHODS The Women 's Health Initiative estrogen trial enrolled 10 739 women aged 50 to 79 years without a uterus . Participants were r and omly assigned to receive conjugated equine estrogen ( 0.625 mg/d ) or placebo . RESULTS During a mean of 7.1 years , VT occurred in 111 women r and omly assigned to receive estrogen ( 3.0 per 1000 person-years ) and 86 r and omly assigned to receive placebo ( 2.2 per 1000 person-years ; hazard ratio , 1.32 ; 95 % confidence interval , 0.99 - 1.75 ) . Deep venous thrombosis was reported in 85 women r and omly assigned to receive estrogen ( 2.3 per 1000 person-years ) and 59 r and omly assigned to receive placebo ( 1.5 per 1000 person-years ; hazard ratio , 1.47 ; 95 % confidence interval , 1.06 - 2.06 ) . The VT risk was highest in the first 2 years . There were no significant interactions between estrogen use and age , body mass index , or most other VT risk factors . Comparison of Women 's Health Initiative VT findings for estrogen and previous Women 's Health Initiative findings for estrogen plus progestin showed that the hazard ratios for estrogen plus progestin were significantly higher than those for estrogen alone ( P = .03 ) , even after adjusting for VT risk factors . CONCLUSION An early increased VT risk is associated with use of estrogen , especially within the first 2 years , but this risk increase is less than that for estrogen plus progestin", "CONTEXT Observational studies have found lower rates of coronary heart disease ( CHD ) in postmenopausal women who take estrogen than in women who do not , but this potential benefit has not been confirmed in clinical trials . OBJECTIVE To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease . DESIGN R and omized , blinded , placebo-controlled secondary prevention trial . SETTING Outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 women with coronary disease , younger than 80 years , and postmenopausal with an intact uterus . Mean age was 66.7 years . INTERVENTION Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . Follow-up averaged 4.1 years ; 82 % of those assigned to hormone treatment were taking it at the end of 1 year , and 75 % at the end of 3 years . MAIN OUTCOME MEASURES The primary outcome was the occurrence of nonfatal myocardial infa rct ion ( MI ) or CHD death . Secondary cardiovascular outcomes included coronary revascularization , unstable angina , congestive heart failure , resuscitated cardiac arrest , stroke or transient ischemic attack , and peripheral arterial disease . All-cause mortality was also considered . RESULTS Overall , there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes : 172 women in the hormone group and 176 women in the placebo group had MI or CHD death ( relative hazard [ RH ] , 0.99 ; 95 % confidence interval [ CI ] , 0.80 - 1.22 ) . The lack of an overall effect occurred despite a net 11 % lower low-density lipoprotein cholesterol level and 10 % higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group ( each P CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5 . More women in the hormone group than in the placebo group experienced venous thromboembolic events ( 34 vs 12 ; RH , 2.89 ; 95 % CI , 1.50 - 5.58 ) and gallbladder disease ( 84 vs 62 ; RH , 1.38 ; 95 % CI , 1.00 - 1.92 ) . There were no significant differences in several other end points for which power was limited , including fracture , cancer , and total mortality ( 131 vs 123 deaths ; RH , 1.08 ; 95 % CI , 0.84 - 1.38 ) . CONCLUSIONS During an average follow-up of 4.1 years , treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease . The treatment did increase the rate of thromboembolic events and gallbladder disease . Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events , we do not recommend starting this treatment for the purpose of secondary prevention of CHD . However , given the favorable pattern of CHD events after several years of therapy , it could be appropriate for women already receiving this treatment to continue", "Premenopausal women have a relatively lower risk of ischemic heart disease ( IHD ) compared to age matched men and this gender gap narrows after menopause . The observation that the onset of IHD occurs 10 years later in women than it does in men is said to suggest that endogenous reproductive hormones play a protective role . Indeed , animal models and human epidemiological studies suggest that oophorectomy is a risk factor for accelerated IHD . In animal models , hormone therapy ( HT ) has anti-atherosclerotic effects after oophorectomy , HT in the form of oral contraceptives ( OCs ) prevents atherosclerosis in anovulatory cycling women , and large numbers of premenopausal women taking OCs have relative safety from an IHD st and point ( 1 ) . Further , observational epidemiological studies in humans have consistently demonstrated protective effects for IHD among HT users . Such studies are typically performed on relatively younger women where HT is prescribed for vasomotor symptoms during menopausal transition or shortly following menopause . In contrast , clinical trials in older , postmenopausal and often asymptomatic women have demonstrated no overall benefit and early adverse effects when r and omized to a variety of forms of HT ( 1 ) . These data discrepancies have called into question the validity of the reproductive hormone estrogen protection hypothesis , and raise the alternative possibility that HT efficacy may differ according to the timing of exposure . Stated as a simple question , is the effect of HT on the risk of IHD in relatively young pre- or early menopausal women with vasomotor symptoms , different than it is in older , fully menopausal women ? Data from the Women ’s Ischemia Syndrome Evaluation ( WISE ) , a prospect i ve multi-center NHLBI-sponsored study design ed to explore female-specific pathophysiology in a large sample of women undergoing coronary angiography for suspected IHD ( 2 ) , may shed light on this controversy . These new data , prospect ively obtained using novel methods , including detailed reproductive health question naires , menopausal adjudication algorithms , and quantitative coronary angiography as a measure of atherosclerosis , allow a more precise inspection of this question . However , to answer this simple question we need to first answer others . Specifically , how can we integrate and underst and the findings from the available observational , animal and clinical trial data ? And to interpret these data other questions become relevant : 1 ) How accurately was menopause assessed in prior observational HT studies ? 2 ) Does HT in premenopausal women in the form of OC therapy confirm atherosclerosis benefit ? and 3 ) Does HT in early menopausal women confer reduced atherosclerosis and benefit on the risk of IHD ", "Objective : To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years . Design : This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial , a r and omized , placebo-controlled , double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol . Four hundred seventeen postmenopausal women , aged 60 to 80 years , were r and omly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d ( n = 208 ) or placebo ( n = 209 ) . Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a st and ardized question naire . Results : At baseline , 16 % of women reported hot flashes , 32 % reported vaginal dryness , and 35 % reported trouble sleeping . Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes , vaginal dryness , or sleep difficulties than those who received placebo . Treatment with ultralow-dose estradiol did not cause breast tenderness , uterine bleeding , or other symptoms often attributed to estrogen , but vaginal discharge was more common in women who received estradiol compared with those who received placebo . Conclusion : In this population of older , largely asymptomatic women , ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge . Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger , more symptomatic women", "R and omized , controlled trial data from the Heart and Estrogen-progestin Replacement Study were used to evaluate the effect of estrogen plus progestin use on all-cause mortality in women with heart failure and coronary disease . Over the 4.1-year follow-up , estrogen plus progestin use had no effect on all-cause mortality ( hazard ratio 1.0 , 95 % confidence interval 0.7 to 1.4 , p = 0.8 ) in women with heart failure and coronary disease", "Abstract . A 2‐year double‐blind trial design ed for study ing the separate and combined effects of bendroflumethiazide ( BFTZ ) and cyclical administration of 17β‐estradiol + estriol/norethisterone ( E/N ) on coronary risk factors and bone mineral loss ( reported elsewhere ) was undertaken . Serum lipids , fasting blood glucose , body weight and blood pressure were measured every 3 months in 97 normal women in their early menopause . All participants received a supplement of 500 mg calcium and were r and omized to one of the following treatment groups : 1 ) placebo ( P ) + P ( n = 33 ) ; 2 ) P + E/N ( n = 21 ) ; 3 ) BFTZ + E/N ( n = 22 ) ; and 4 ) BFTZ + P ( n = 21 )", "OBJECTIVES Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life ( QOL ) . The aims of this study were to measure menopausal symptoms , mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators . METHODS A prospect i ve , r and omized , placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms , anxiety and depressive symptoms , and QOL in 152 postmenopausal women over a 12 month study period . Menopausal symptoms were measured using a modified Kupperman 's scale . Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life question naire , respectively . RESULTS Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high . Over 12 months , after adjustment for differences in baseline scoring , there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group . There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo . CONCLUSIONS These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood . In addition , the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians . Therefore , when considering the reasons for prescribing hormone replacement therapy in this population , protection against osteoporosis will for most women be the prime consideration", "Objective : To examine whether the effect of postmenopausal hormone therapy ( HT ) on brain volumes in women aged 65–79 years differs depending on type 2 diabetes status during postintervention follow-up of a r and omized controlled clinical trial . Methods : The Women 's Health Initiative r and omized clinical trials assigned women to HT ( 0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate ) or placebo for an average of 5.6 years . A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials ; these were repeated in 699 women 4.7 years later . General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes . Results : Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of −18.6 mL ( 95 % confidence interval [ CI ] −29.6 , −7.6 ) . For women without diabetes , this mean decrement was −0.4 ( 95 % CI −3.8 , 3.0 ) ( interaction p = 0.002 ) . This interaction was evident for total gray matter ( p and hippocampal ( p = 0.006 ) volumes . It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications . Conclusions : For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes , prescription of postmenopausal HT is associated with lower gray matter ( total and hippocampal ) volumes . Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women", "BACKGROUND Although the Women 's Health Initiative ( WHI ) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group , the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer . We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants . METHODS In the WHI trial , 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were r and omly assigned to a combination of conjugated equine estrogens ( 0.625 mg per day ) plus medroxyprogesterone acetate ( 2.5 mg per day ) or placebo . The main outcome measures were the incidence , stages , and types of colorectal cancer , as determined by blinded central adjudication . RESULTS There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group ( hazard ratio , 0.56 ; 95 percent confidence interval , 0.38 to 0.81 ; P=0.003 ) . The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes ( mean + /-SD , 3.2+/-4.1 vs. 0.8+/-1.7 ; P=0.002 ) and were more advanced ( regional or metastatic disease , 76.2 percent vs. 48.5 percent ; P=0.004 ) . In exploratory analyses , women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding ( 3.8+/-4.3 vs. 0.7+/-1.5 nodes , P=0.006 ) . CONCLUSIONS Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer . However , colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo", "OBJECTIVE : To estimate the effect of 2 years of treatment with ultralow-dose transdermal estradiol ( E2 ) on incontinence in postmenopausal women . METHODS : Ultra Low Dose Transdermal estRogen Assessment ( ULTRA ) was a multicenter , r and omized , double-blinded , placebo-controlled trial of unopposed ultralow-dose ( 0.014 mg/d ) transdermal E2 for prevention of osteoporosis in 417 postmenopausal women aged 60 to 80 years . Frequency of incontinence episodes was assessed at baseline and after 4 months and 2 years of treatment using a self-reported question naire . We used an intention-to-treat analysis to compare change in incontinence frequency , improved ( decreased 2 or more episodes per week ) , unchanged ( increased or decreased no more than 1 episode per week ) , or worsened ( increased 2 or more episodes per week ) between the E2 and placebo groups among women with and without at least weekly incontinence at baseline . RESULTS : At baseline , the prevalence of at least weekly incontinence was similar between E2 and placebo groups ( 43 % ) . After 2 years , there was no difference between groups in the proportions of women with incontinence at baseline whose incontinence improved , worsened , or was unchanged . The odds ratio for worsening incontinence in the E2 compared with placebo group was 1.35 ( 95 % confidence interval 0.75–2.42 . In women without incontinence at baseline , the odds of developing at least weekly incontinence after 2 years in the E2 compared with placebo group was not significant ( odds ratio 1.2 , 95 % confidence interval 0.7–2.2 ) . CONCLUSION : Two years of treatment with unopposed ultralow-dose transdermal E2 did not substantially change the frequency of incontinence symptoms or alter the risk of developing at least weekly incontinence . LEVEL OF EVIDENCE :", "OBJECTIVES To evaluate the effect of ultra-low-dose ( 0.25 mg/d ) micronized 17beta-estradiol on cognitive function in older postmenopausal women . DESIGN R and omized , placebo-controlled trial conducted for 3 years . SETTING Academic health center in greater Hartford , Connecticut . PARTICIPANTS Fifty-seven healthy , community-dwelling , older postmenopausal women . INTERVENTION Women received 0.25 mg/d of micronized 17beta-estradiol ( estrogen therapy ( ET ) , n=32 ) or placebo ( n=25 ) ; all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months . MEASUREMENTS Neuropsychological measures of memory , language , mood , and executive function were collected at baseline , 3 months , and 36 months . Measures of executive function included the Controlled Oral Word Association Test , the Trail Making Test , and the Wisconsin Card Sorting Test . The Boston Naming Test was used to measure language skills . The Symbol Digit Modalities Test was used as a measure of sustained attention . Measures of memory included the Complex Figure Test , Fuld Object Memory Test , and a selected subtest from the Wechsler Memory Scale . Scores from the Geriatric Depression Scale and the Beck Anxiety Inventory were used to assess symptoms of depression . RESULTS No differences were found between ET and placebo on any of the neurocognitive measures or depression instruments , nor were there any differences when the groups were stratified according to age . CONCLUSION This small study , which had adequate power to detect change in some but not all domains of cognition tested , revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment , but confirmation is needed from larger trials", "Context Risk factors for recurrent events among women with known coronary disease and whether these women commonly receive secondary prevention treatments are mostly unknown . Contribution This large cohort study showed that 11 different factors , including several previous infa rct ions , renal dysfunction , diabetes , angina , heart failure , and uncontrolled hypertension , predicted up to a sixfold increased rate of coronary disease events in postmenopausal women with preexisting coronary disblockers , angiotensin-converting enzyme inhibitors , or cholesterol-lowering drugs . Implication s Clinicians can identify women who have high risks for recurrent coronary events and should promote greater use of secondary prevention treatments for them . The Editors Coronary heart disease ( CHD ) is the leading cause of death in women . The major independent risk factors that predict CHD onset in healthy women are similar to those identified by epidemiologic studies of healthy men ( 1 - 7 ) . A recent report described six independent risk factorsage , low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol levels , high blood pressure , diabetes mellitus , and smokingthat were strongly associated with risk for a first CHD event in both men and women ( 8) . However , the strength of the association of certain risk factors with CHD events may vary by sex ( 9 ) as well as age . Diabetes may be a stronger risk factor in women than in men ( 7 ) ; among older women , HDL cholesterol level may be a relatively strong risk factor and LDL cholesterol level a relatively weak one ( 6 ) . In the period immediately after myocardial infa rct ion ( MI ) , studies of mostly male sample s have found that persistent ischemia , impaired left ventricular systolic function , and ventricular arrhythmias are the major determinants of subsequent MI and death ( 10 - 13 ) . In the Coronary Drug Project study of men with a history of heart attack , electrocardiographic abnormalities and heart failure were stronger predictors than the atherosclerosis risk factors identified in primary prevention setting s ( 14 ) . However , the risk factors for coronary events among women with recognized but stable coronary disease are mostly unknown . Better underst and ing of these factors could improve secondary prevention in this large and high-risk group . The Heart and Estrogen/progestin Replacement Study ( HERS ) was a r and omized clinical trial of estrogen plus progestin for prevention of CHD events in women with coronary disease ( 15 ) . Overall , no significant differences were noted between the hormone and placebo groups in CHD events ; trends of more CHD events with therapy in year 1 were offset by fewer such outcomes during years 4 and 5 . The trial collected extensive data on CHD risk factors and medication use and performed exhaustive outcome ascertainment procedures , with complete mortality follow-up . Therefore , HERS offers a unique opportunity to assess the long-term effect of coronary risk factors and use of recommended treatments in women with established coronary disease . Methods Participants Participants in HERS were postmenopausal women who were younger than 80 years of age , had not had a hysterectomy , and had known coronary artery disease ( MI , coronary artery bypass surgery , percutaneous transluminal coronary angioplasty , or angiographic evidence of 50 % narrowing of one or more major coronary arteries ) . Women were excluded if they had had a coronary event within the 6 months before r and omization , had a serum triglyceride level greater than 3.39 mmol/L ( 300 mg/dL ) , had used hormones within 3 months , or had a history of conditions that would contraindicate estrogen therapy ( 16 ) . Participants in HERS were r and omly assigned within clinical centers to 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate in one tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . The institutional review boards at the coordinating center and each of the 20 HERS clinical centers approved the protocol , and all participants provided written informed consent . Predictors In the baseline interview , information was obtained by self-report on demographic characteristics , behavioral risk factors , and medical history . Among women who reported ever having smoked at least 100 cigarettes , years of smoking , average cigarettes per day , and current smoking were ascertained . Alcohol use in the past 30 days was assessed for frequency and usual numbers of drinks per occasion . Exercise was measured as participation in a regular exercise program such as cardiac rehabilitation or aerobics or walking at least occasionally for exercise more than 10 minutes at a time . Use of aspirin , -blockers , lipid-lowering medications ( statins , niacin , fibrates , bile acidbinding resins , and probucol ) , angiotensin-converting enzyme ( ACE ) inhibitors , calcium antagonists , and folate or vitamin B was assessed by self-report . In the baseline physical examination , blood pressure , waist-to-hip ratio , and body mass index were measured . A physician assessed history and symptoms of heart failure ( jugular venous distention , third heart sound , significant murmurs , pulmonary rales , and peripheral edema ) . High blood pressure was defined as systolic blood pressure greater than or equal to 140 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg , according to the Sixth Report of the Joint National Committee on Prevention , Detection , Evaluation and Treatment of High Blood Pressure ( 17 ) . Angina was defined as self-report of chest discomfort in the previous 4 weeks during exercise , emotion , or sexual activity . Serum specimens were obtained , and a central ized laboratory measured fasting levels of LDL cholesterol , HDL cholesterol , lipoprotein(a ) , triglycerides , glucose , and creatinine ( 15 , 16 ) . Creatinine clearance was estimated by using the CockcroftGault equation ( 18 , 19 ) . Outcomes The primary HERS outcome was CHD events , defined as nonfatal MI or CHD death . Suspected outcome events were reported within 24 hours to the coordinating center and were systematic ally assessed every 4 months at the follow-up contacts . An independent morbidity and mortality subcommittee that was blinded to treatment assignment adjudicated all deaths and suspected outcome events . Nonfatal MI was diagnosed by using an algorithm based on ischemic symptoms , electrocardiographic abnormalities , and elevated cardiac enzyme levels ( 16 ) . Death from CHD included fatal documented MI , sudden death within 1 hour of symptom onset , unobserved death that occurred out of the hospital in the absence of other known causes , or death due to a coronary revascularization procedure or congestive heart failure . The date of each event was determined from the documentation obtained by the clinical centers . The total number of events reported here is slightly larger than that published in the primary HERS results ( 15 ) because of subsequent adjudications ( 20 ) . Statistical Analyses We used multivariable Cox proportional-hazards models to assess the associations between risk factors and CHD events . These models were stratified by clinical center to account for potential clustering . Waist-to-hip ratio and LDL and HDL cholesterol levels were modeled as continuous variables , but lipoprotein(a ) level was dichotomized at the median and creatinine clearance was dichotomized at 0.66 mL/s ( 40 mL/min ) to reflect the nonlinear responses we have reported elsewhere ( 19 , 21 ) . We used an indicator for any alcohol use , since almost all of the 39 % of HERS women who reported alcohol use were light or moderate drinkers . Exercise was modeled by an indicator for participation in an exercise program or walking for exercise for more than 10 minutes . The multivariable model includes previously identified risk factors that were significant ( P 0.20 ) in unadjusted models and were not judged redundant on substantive grounds . Body mass index was excluded because it was clearly nonsignificant after adjustment ( P > 0.2 ) and was also highly correlated with waist-to-hip ratio , which was the stronger predictor in unadjusted analysis . Similarly , triglyceride levels were excluded because of their strong negative correlation with HDL cholesterol levels , which in our judgment were more likely to be causal . We also controlled for use of aspirin , statins , other lipid-lowering medications , diuretics , -blockers , ACE inhibitors , calcium antagonists , and folate or vitamin B. The effect of assignment to hormone therapy was modeled separately for each year of follow-up , as in the post hoc analysis of HERS ( 15 ) . Interactions between risk factors and relevant treatments were also examined . Specifically , we compared hazard rates among patients with diagnosed diabetes who reported use of insulin or oral hypoglycemic agents with rates in the combined group of diabetic persons not using these medications and women with fasting glucose levels greater than 6.94 mmol/L ( > 125 mg/dL ) but no history of diabetes diagnosis . Likewise , we compared estimates for LDL and HDL cholesterol levels stratified by use of any lipid-lowering medication or assignment to hormone therapy ; for lipoprotein(a ) level , stratified by assignment to hormone therapy ; for high blood pressure on examination , stratified by use of at least one antihypertensive medication ; for heart failure and creatinine clearance less than or equal to 0.66 mL/s ( 40 mL/min ) , stratified by use of ACE inhibitors ; and for more than one previous MI and angina , stratified by use of any indicated medications . The final model includes interactions that were significant at a P value less than or equal to 0.2 . We used residuals to assess overall model fit , validity of the proportional hazards assumption , and linearity of associations with continuous predictors . The study lacked power to examine interactions between clinical center and potential risk factors . We tested the assumption of noninformative censoring by considering the two extremes of the possible outcomes", "OBJECTIVE Our purpose was to investigate the long-term effects of raloxifene , compared with opposed and unopposed estrogen replacement therapy , on echocardiographic parameters of left ventricular systolic function in healthy postmenopausal women . A total of 157 women were studied in 2 r and omized , double-blind , placebo-controlled , 2-year studies . STUDY DESIGN In study I , 60 postmenopausal women who had undergone hysterectomy received daily raloxifene , 60 mg ( n = 15 ) ; raloxifene , 150 mg ( n = 15 ) ; conjugated equine estrogens ( CEE ) , 0.625 mg ( n = 15 ) ; or placebo ( n = 15 ) . In study II , 97 postmenopausal women who had not undergone hysterectomy received daily raloxifene , 60 mg ( n = 24 ) ; raloxifene , 150 mg ( n = 24 ) ; CEE , 0.625 mg , plus medroxyprogesterone acetate ( MPA ) , 2.5 mg ( n = 24 ) ; or placebo ( n = 25 ) . M-mode , quantitative 2-dimensional and Doppler echocardiographic measurements were performed at baseline and after 1 and 2 years . RESULTS Neither after 1 year nor after 2 years of treatment were echocardiographic parameters found to differ from baseline in both raloxifene groups , as well as in the unopposed CEE and the CEE/MPA groups , compared with the placebo group . CONCLUSION Within 2 years of raloxifene treatment , no effect on echocardiographic parameters of left ventricular systolic function was found . Unopposed CEE or CEE/MPA also showed no effect", "PURPOSE During the intervention phase in the Women 's Health Initiative ( WHI ) clinical trial , use of estrogen plus progestin reduced the colorectal cancer diagnosis rate , but the cancers were found at a substantially higher stage . To assess the clinical relevance of the findings , analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up . PATIENTS AND METHODS The WHI study was a r and omized , double-blind , placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were r and omly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate ( n = 8,506 ) or matching placebo ( n = 8,102 ) . Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed . RESULTS After a mean of 5.6 years ( st and ard deviation [ SD ] , 1.03 years ) of intervention and 11.6 years ( SD , 3.1 years ) of total follow-up , fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group ( diagnoses/year , 0.12 % v 0.16 % ; hazard ratio [ HR ] , 0.72 ; 95 % CI , 0.56 to 0.94 ; P = .014 ) . Bowel screening examinations were comparable between groups throughout . Cancers in the combined hormone therapy group more commonly had positive lymph nodes ( 50.5 % v 28.6 % ; P stage ( regional or distant , 68.8 % v 51.4 % ; P = .003 ) . Although not statistically significant , there was a higher number of colorectal cancer deaths in the combined hormone therapy group ( 37 v 27 deaths ; 0.04 % v 0.03 % ; HR , 1.29 ; 95 % CI , 0.78 to 2.11 ; P = .320 ) . CONCLUSION The findings , suggestive of diagnostic delay , do not support a clinical ly meaningful benefit for combined hormone therapy on colorectal cancer", "Objective To assess the possible benefit of hormone replacement therapy ( HRT ) in the secondary prevention of ischaemic heart disease ", "The Women 's Health Initiative Memory Study -Younger ( WHIMS-Y ) was design ed to assess the effect of prior r and om assignment to hormone therapy ( HT ) ( conjugated equine estrogen ( CEE ) alone or CEE plus medroxyprogesterone acetate ( MPA ) ) on global cognitive function in younger middle-aged women relative to placebo . WHIMS-Y was an ancillary study to the Women 's Health Initiative ( WHI ) HT trial and enrolled 1361 women who were aged 50 - 55 years and postmenopausal at WHI enrollment . WHIMS-Y will examine whether an average of 5.4 years of HT during early menopause has longer term protective effects on global cognitive function and if these effects vary by regimen , time between menopause and study initiation , and prior use of HT . We present the study rationale and design . We describe enrollment , adherence to assigned WHI therapy , and compare risk factor characteristics of the WHIMS-Y cohort at the time of WHI enrollment to similar aged women in the WHI HT who did not enroll in WHIMS-Y. Challenges of WHIMS-Y include lower than expected and differential enrollment . Strengths of WHIMS-Y include balance in baseline risk factors between treatment groups , st and ardized and masked data collection , and high rates of retention and on-trial adherence and exposure . In addition , the telephone-administered cognitive battery showed adequate construct validity . WHIMS-Y provided an unprecedented chance to examine the hypothesis that HT may have protective effects on cognition in younger postmenopausal women aged 50 - 55 years . Integrated into the WHI , WHIMS-Y optimized the experience of WHI investigators to ensure high retention and excellent quality assurance across sites . This article is part of a Special Issue entitled Hormone Therapy", "BACKGROUND In the Women 's Health Initiative ( WHI ) r and omized controlled trial , use of estrogen plus progestin increased lung cancer mortality . We conducted post hoc analyses in the WHI trial evaluating estrogen alone to determine whether use of conjugated equine estrogen without progestin had a similar adverse influence on lung cancer . METHODS The WHI study is a r and omized , double-blind , placebo-controlled trial conducted in 40 centers in the United States . A total of 10 739 postmenopausal women aged 50 - 79 years who had a previous hysterectomy were r and omly assigned to receive a once-daily 0.625-mg tablet of conjugated equine estrogen ( n = 5310 ) or matching placebo ( n = 5429 ) . Incidence and mortality rates for all lung cancers , small cell lung cancers , and non-small cell lung cancers in the two r and omization groups were compared by use of hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) that were estimated from Cox proportional hazards regression analyses . Analyses were by intention to treat , and all statistical tests were two-sided . RESULTS After a mean of 7.9 years ( st and ard deviation = 1.8 years ) of follow-up , 61 women in the hormone therapy group were diagnosed with lung cancer compared with 54 in the placebo group ( incidence of lung cancer per year = 0.15 % vs 0.13 % , respectively ; HR of incidence = 1.17 , 95 % CI = 0.81 to 1.69 , P = .39 ) . Non-small cell lung cancers were of comparable number , stage , and grade in both groups . Deaths from lung cancer did not differ between the two groups ( 34 vs 33 deaths in estrogen and placebo groups , respectively ; HR of death = 1.07 , 95 % CI = 0.66 to 1.72 , P = .79 ) . CONCLUSION Unlike use of estrogen plus progestin , which increased deaths from lung cancer , use of conjugated equine estrogen alone did not increase incidence or death from lung cancer", "OBJECTIVE To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures . DESIGN Double-blind , r and omized , placebo-controlled clinical trial lasting 1 year . SETTING Referral-based outpatient clinic . PATIENTS Seventy-five postmenopausal women , 47 to 75 years of age , with one or more vertebral fractures due to osteoporosis . INTERVENTIONS Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle . Another 39 women received placebo . MEASUREMENTS Bone turnover assessed by biochemical markers and iliac bone histomorphometry ; bone loss assessed by serial measurement of bone density ; and vertebral fracture rate . RESULTS Compared with the placebo group , the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine ( 5.3 compared with 0.2 ; P = 0.007 ) , femoral trochanter ( 7.6 compared with 2.1 ; P = 0.03 ) , and midradius ( 1.0 compared with -2.6 , P less than 0.001 ) but showed no significant difference at the femoral neck ( 2.6 compared with 1.4 ; P = 0.17 ) . Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration ( median change , -0.35 compared with 0.02 nmol/L ; P less than 0.001 ) . Histomorphometric evaluation of iliac biopsy sample s confirmed the effect of estrogen on bone formation rate per bone volume ( median change , -12.9 compared with -6.2 % per year ; P = 0.004 ) . Also , 8 new fractures occurred in 7 women in the estrogen group , whereas 20 occurred in 12 women in the placebo group , yielding a lower vertebral fracture rate in the estrogen group ( relative risk , 0.39 ; 95 % CI , 0.16 to 0.95 ) . CONCLUSIONS Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis", "Objectives This 2-year study compared 0.5 and 1.0 mg oral estradiol ( E2 ) , with or without levonorgestrel ( LNG ) , for the treatment of postmenopausal osteoporosis in Japanese women . Methods Japanese women with osteoporosis after natural menopause or bilateral oophorectomy were r and omized to receive E2 0.5 or 1.0 mg/day with LNG 40 μg as required , or placebo , for 52 weeks . Women treated with E2 in the first year continued therapy at the same doses in the second year . Efficacy , safety and pharmacokinetics were assessed . Results There were 73 women r and omized to E2 0.5 mg , 157 to E2 1.0 mg and 79 to placebo . Lumbar bone mineral density at 52 weeks increased significantly more with E2 1.0 mg ( p with placebo ( no change ) . After 2 years , a 10 % increase in bone mineral density with E2 1.0 mg was significantly greater than with E2 0.5 mg ( 8 % ; p = 0.008 ) . E2 was associated with an acceptable safety and tolerability profile , with slightly more adverse events with E2 1.0 than 0.5 mg . Serum E2 concentration increased in a dose-dependent manner . Conclusion This study showed that E2 , at both 1.0 mg and 0.5 mg doses , was effective in increasing bone mineral density with an acceptable safety and tolerability profile in Japanese postmenopausal women with osteoporosis but that the bone mineral density response was higher with the 1.0 mg dose", "Surgery for premenopausal and perimenopausal patients with epithelial ovarian carcinoma may often result in significant menopausal symptoms . Physicians may well be reluctant to prescribe , and patients loathe to take , postoperative estrogen replacement therapy because they fear that supplementation may lead to ovarian carcinoma relapse . This r and omized prospect i ve study was undertaken to determine whether postoperative estrogen replacement therapy had a negative influence on the disease free interval and overall survival of ovarian carcinoma survivors", "Despite several observational studies , 1–3 no clinical trial has evaluated the effect of hormone therapy on percutaneous transluminal coronary angioplasty ( PTCA ) outcomes in matched population s r and omized to hormones or placebo . We compared the incidence of coronary heart disease ( CHD ) events after PTCA among women who previously had been r and omly assigned to hormone therapy and placebo in the Heart and Estrogen/progestin Replacement Study ( HERS ) .  The design , methods , and primary results of HERS have been previously published . 4,5 Briefl y , HERS participants were postmenopausal women aged 80 years with established CHD who had not had a hysterectomy . Inclusion criteria were prior myocardial infa rct ion , coronary artery bypass graft surgery ( CABG ) , PTCA , or angiographic evidence of a 50 % diameter narrowing of 1 major coronary artery . Exclusion criteria were a recent CHD event , New York Heart Association class IV or severe class III congestive heart failure , serum triglyceride levels 300 mg/ dl , recent use of any hormone therapy , uncontrolled hypertension or diabetes , a disease ( other than CHD ) judged likely to be fatal within 4 years , or prior intolerance to hormone therapy . At the initiation of the HERS , participants were r and omly assigned to receive a single identical tablet containing either conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg or placebo . During the HERS , 357 patients underwent PCTA and constituted the study population . These patients were followed subsequently to ascertain their rate for subsequent CHD events . Demographic characteristics , health history , CHD risk factors , medication use , educational level , and quality of life were assessed at baseline . Baseline levels of fasting total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , and lipoprotein ( a ) were determined by the Lipoprotein Analytical Laboratory at Johns Hopkins Hospital ( Baltimore , Maryl and ) . Follow-up time for this analysis began at the time of the initial PTCA and concluded at the closeout of the HERS . All suspected outcome events were classifi ed independently by 2 physician review ers who were unaware of treatment assignment . Discordant classifi cations were resolved in discussion s between the review ers", "CONTEXT The Women 's Health Initiative ( WHI ) trial of estrogen plus progestin vs placebo was stopped early , after a mean 5.6 years of follow-up , because the overall health risks of hormone therapy exceeded its benefits . OBJECTIVE To report health outcomes at 3 years ( mean 2.4 years of follow-up ) after the intervention was stopped . DESIGN , SETTING , AND PARTICIPANTS The intervention phase was a double-blind , placebo-controlled , r and omized trial of conjugated equine estrogens ( CEE ) 0.625 mg daily plus medroxyprogesterone acetate ( MPA ) 2.5 mg daily , in 16,608 women aged 50 through 79 years , recruited by 40 centers from 1993 to 1998 . The postintervention phase commenced July 8 , 2002 , and included 15 730 women . MAIN OUTCOME MEASURES Semi-annual monitoring and outcomes ascertainment continued per trial protocol . The primary end points were coronary heart disease and invasive breast cancer . A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke , pulmonary embolism , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS The risk of cardiovascular events after the intervention was comparable by initial r and omized assignments , 1.97 % ( annualized rate ) in the CEE plus MPA ( 343 events ) and 1.91 % in the placebo group ( 323 events ) . A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group ( 1.56 % [ n = 281 ] vs 1.26 % [ n = 218 ] ; hazard ratio [ HR ] , 1.24 ; 95 % confidence interval [ CI ] , 1.04 - 1.48 ) . More breast cancers were diagnosed in women who had been r and omly assigned to receive CEE plus MPA vs placebo ( 0.42 % [ n = 79 ] vs 0.33 % [ n = 60 ] ; HR , 1.27 ; 95 % CI , 0.91 - 1.78 ) with a modest trend toward a lower HR during the follow-up after the intervention . All-cause mortality was somewhat higher in the CEE plus MPA than in the placebo group ( 1.20 % [ n = 233 ] vs 1.06 % [ n = 196 ] ; HR , 1.15 ; 95 % CI , 0.95 - 1.39 ) . The global index of risks and benefits was unchanged from r and omization through March 31 , 2005 ( HR , 1.12 ; 95 % CI , 1.03 - 1.21 ) , indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention . CONCLUSIONS The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention . A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12 % higher in women r and omly assigned to receive CEE plus MPA compared with placebo . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "Objective : To investigate factors associated with the presence , severity , and frequency of hot flushes . Design : A 9-year prospect i ve study of 438 Australian-born women , aged 45 to 55 years and menstruating at baseline . Annual fasting blood collection , physical measurements , and interviews including questions about bothersome hot flushes in previous 2 weeks were performed . A “ hot flush index ” score was calculated from the product of the severity and frequency data . Data were analyzed using r and om-effects time-series regression models . Results : A total of 381 women supplied complete data over the follow-up years . A total of 350 women experienced the menopause transition , of whom 60 ( 17 % ) never reported bothersome hot flushes . At baseline , women who reported hot flushes were significantly more likely to have higher negative moods , not be in full- or part-time paid work , smoke , and not report exercising every day . Over the 9-year period of the study , variables significantly associated with reporting bothersome hot flushes were relatively young age ( P low exercise levels ( P low estradiol levels ( P follicle-stimulating hormone ( FSH ) levels ( P smoking ( P the late menopause transition ( P postmenopausal ( P hot flush index score increased as their FSH levels increased ( P age ( P exercise level ( P hot flush index score was greater in women with higher average FSH levels over time ( P FSH and estradiol levels , age , exercise level , and smoking status all contributed to the experience of bothersome hot flushes", "Objective This study aims to present methods and baseline data from the Early versus Late Intervention Trial with Estradiol ( ELITE ) , the only clinical trial design ed to specifically test the timing hypothesis of postmenopausal hormone therapy ( HT ) . The timing hypothesis posits that HT effects depend on the temporal initiation of HT relative to time since menopause . Methods ELITE is a r and omized , double-blind , placebo-controlled trial with a 2 × 2 factorial design . Six hundred forty-three healthy postmenopausal women without cardiovascular disease were r and omized to oral estradiol or placebo for up to 6 to 7 years according to time since menopause ( y ) . Carotid artery intima-media thickness ( CIMT ) and cardiac computed tomography were conducted to determine HT effects on sub clinical atherosclerosis across menopause strata . Results Participants in the early and late postmenopausal strata were well-separated by mean age ( 55.4 vs 65.4 y ) and median time since menopause ( 3.5 vs 14.3 y ) . Expected risk factors ( age , blood pressure , and body mass index ) were associated with CIMT at baseline in both strata . In the early postmenopausal group , but not in the late postmenopausal group , we observed significant associations between CIMT and factors that may play a role in the responsiveness of atherosclerosis progression according to timing of HT initiation . These include low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , sex hormone – binding globulin , and serum total estradiol . Conclusions The ELITE r and omized controlled trial is timely and unique . Baseline data indicate that ELITE is well-positioned to test the HT timing hypothesis in relation to atherosclerosis progression and coronary artery disease ", "To eluci date the effect of smoking on estrogen metabolism , we examined 136 postmenopausal women treated for one year with one of three different doses of combined estrogen-progestogen or placebo . The women were grouped according to smoking status , and serum levels of estrone and estradiol were measured before and after treatment . The results showed reduced levels of both estrogens in smokers as compared with nonsmokers in all three dosage groups . This reduction was most pronounced in the high-dose group ( 4 mg of estradiol ) , in which the serum levels of estrone and estradiol in smokers were only 50 per cent of those in nonsmokers ( P less than 0.001 and less than 0.05 , respectively ) . In contrast , no significant changes could be demonstrated in the corresponding placebo groups . Moreover , it was possible to demonstrate significant inverse correlations between the number of cigarettes smoked daily and the changes in the levels of serum estrone and estradiol , respectively , ( P less than 0.001 ) . This study suggests that an increased hepatic metabolism of estrogens results in lower estrogen levels among postmenopausal smokers . This may contribute to the reported risk of osteoporosis among smokers", "CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women", "The purpose of this study was to investigate the effects of 10 years of hormone replacement therapy ( HRT ) in postmenopausal women on bone mineral density of the lumbar spine ( L-BMD ) and bone mineral content of the distal forearm ( F- BMC ) . A total of 151 women were enrolled in the study , 100 of whom were r and omized to receive oral HRT ( equally divided between a continuous combined and a sequential treatment regimen ) , with the remaining 51 receiving placebo or no treatment . The study was double-blind for the first 24 months , followed by 8 years of open-label follow-up . Total treatment duration was 10 years . At the end of 10 years , 38 % of women r and omized to continuous combined HRT remained on therapy compared with 22 % of those who had received sequential HRT and 49 % of the untreated group . A further 18 % of women originally r and omized to HRT had switched to other regimens . After 10 years of therapy , L-BMD was found to be significantly higher in HRT-treated women than in those who remained untreated ( 14.5 % ; p L-BMD of 13.1 % from baseline values on HRT compared with a reduction in L-BMD of 4.7 % without therapy . L-BMD increased by 15.9 % in women receiving continuous combined therapy compared with 11.1 % in those on sequential HRT ; however , intergroup differences were not statistically significant . F- BMC decreased by 0.7 % over the 10 year period in the HRT treatment groups compared with a reduction of 17.6 % in untreated women ( p Mean F- BMC was 20.3 % higher in women who had received HRT than in those who had not received therapy at the end of the 10 year follow-up . In conclusion , 10 years of treatment with HRT result ed in a substantial increase in L-BMD , with F- BMC also significantly higher in the HRT group than in untreated women . These results confirm that long-term HRT exerts a continuous effect against bone loss in postmenopausal women", "Objective To determine the lowest effective dose of an estradiol ( E2 ) matrix-type transdermal delivery system ( EMTDS ; Alora ) for preventing bone loss in postmenopausal women . Design This double-blind , double-dummy , r and omized , placebo-controlled , multicenter study enrolled 355 nonosteoporotic postmenopausal women who had been hysterectomized with or without oophorectomy at least 12 months earlier . Participants were r and omly assigned to one of three doses of the EMTDS ( 0.025 , 0.05 , or 0.075 mg/day ) or placebo administered twice weekly . Lumbar bone mineral density ( LBMD ) was measured by dual-energy x-ray absorptiometry at screening and after 1 and 2 years of treatment . Safety was assessed at regularly scheduled visits . Results EMTDS provided statistically significant and clinical ly meaningful changes in LBMD relative to placebo . At 2 years , LBMD declined from baseline by 0.59 % in the placebo group , but it increased from baseline by 1.65 % ( p = 0.0065 ) , 4.08 % ( p = 0.0001 ) , and 4.82 % ( p = 0.0001 ) in the EMTDS 0.025 , 0.05 , and 0.075 mg/day groups , respectively . The corresponding responder rates ( defined as no change or increase in LBMD at endpoint ) were 39.7 % for placebo , 59.6 % , 79.3 % , and 83.9 % in the EMTDS 0.025 , 0.05 , and 0.075 mg/day groups , respectively . Mean serum E2 concentrations were proportional to the dose of the E2 transdermal system and did not accumulate over the course of the study . Adverse events were generally comparable across treatment groups , with the majority being mild or moderate in severity and unrelated to study medication . Mammogram findings and other safety assessment s were also comparable across groups and did not reveal any safety concerns with 2-y transdermal E2 treatment . Conclusions The EMTDS ( Alora ) administered twice weekly improves lumbar bone mineral density in healthy postmenopausal women , with the benefit of treatment evident by 1 year . The lowest effective dose is 0.025 mg/day", "OBJECTIVE To assess the efficacy of unopposed estrogen , and three estrogen/progestin regimens on selected heart disease risk factors among adherent women and to contrast those results with efficacy among all women in the PEPI study . DESIGN A 3-year , multicenter , r and omized , double-blinded , placebo-controlled clinical trial . PARTICIPANTS A total of 847 healthy postmenopausal women aged 45 to 64 years of age with no known contraindication to hormone therapy , who attended their 36 month clinical visit . INTERVENTION Participants were r and omized in equal numbers to one of the following treatments : ( 1 ) placebo ; ( 2 ) conjugated equine estrogen ( CEE ) 0.625 mg daily ; ( 3 ) CEE 0.625 daily plus medroxyprogesterone acetate ( MPA ) 10 mg , days 1 - 12 ; ( 4 ) CEE 0.625 daily plus MPA 2.5 mg daily ; or ( 5 ) CEE 0.625 daily plus micronized progesterone ( MP ) 200 mg , days 1 - 12 . ANALYSIS Analyses are based on adherent women , where adherence is defined as taking at least 80 % of pills at each 6-month visit . RESULTS Adherence rates were high in all groups except women with a uterus assigned to unopposed CEE . The difference in HDL-C levels result ing from the CEE vs. CEE+MP was approximately three times larger than in the intent-to-treat analyses , reaching statistical significance ( P LDL-C decreased 10 - 15 % . Triglycerides increased 15 - 20 % in each opposed CEE arm and over 25 % in the CEE only arm ; this difference was not statistically significant . Fibrinogen increased by 7 % among placebo adherers , but decreased or remained fairly stable among the active arm adherers . Systolic blood pressure increased 3 - 5 % in all treatment arms . Women adherent to the CEE+MPA arms had twice the increase of 2 h glucose levels as women adherent to CEE only , or CEE+MP ( 8 - 9 % vs. 3 - 4 % ) . Two-hour insulin levels decreased 3 - 12 % for all arms . The patterns of change for fibrinogen , SBP , 2 h glucose and insulin were similar to those from the intent-to-treat analyses . CONCLUSIONS In analyses limited to adherent women , all active treatments , compared to placebo , continued to have similar and favorable effects on LDL-cholesterol and fibrinogen and no significant effects on blood pressure or insulin levels . Given the overall high adherence rates in PEPI , the results are similar to the intent-to-treat analyses , as expected . Only the trend of HDL-C to have a larger increase in the CEE only arm ( in the intent-to-treat analyses ) gained statistical significance in analyses restricted to adherers", "Objective To determine the relationships among bone mineral density changes , bone marker changes , and plasma estrogens in postmenopausal women receiving estrogen replacement therapy . Design A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens ( 0.3 mg , 0.625 mg , or 1.25 mg ) or placebo daily for up to 24 months . Bone mineral density and bone marker measurements were determined at 6-month intervals ; plasma estrogens were measured in a subset after 12 , 18 , and 24 months . Results Esterified estrogens produced significant increases in bone mineral density ( lumbar spine , hip ) compared with baseline and placebo at 6 , 12 , 18 , and 24 months . Bone markers decreased from baseline with all esterified estrogen doses relative to placebo . Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months ( correlation coefficient range = −0.122 to −0.439 ) . The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin . Mean plasma estrogen levels increased with esterified estrogen dose , and bone mineral density changes correlated positively with plasma estrogen levels . Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL. Conclusions Esterified estrogens , at doses from 0.3 mg to 1.25 mg/day , unopposed by progestin , increase bone mineral density of the spine and hip in postmenopausal women . These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12 , 18 , or 24 months . Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy", "CONTEXT Postmenopausal hormone therapy is commonly used by women for disease prevention , but its effects on quality of life have not been well documented . OBJECTIVE To determine the effect on quality of life of estrogen plus progestin therapy used as secondary prevention in women with coronary artery disease . DESIGN , SETTING , AND PARTICIPANTS A total of 2763 postmenopausal women with documented coronary artery disease ( mean age , 67 years ) in the Heart and Estrogen/Progestin Replacement Study , a r and omized , placebo-controlled , double-blind trial conducted from January 1993 to July 1998 at outpatient and community setting s at 20 US clinical centers . INTERVENTION Participants were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( n = 1380 ) or placebo ( n = 1383 ) for 36 months . MAIN OUTCOME MEASURES Physical activity , measured by the Duke Activity Status Index ; energy/fatigue and mental health , measured by R AND scales ; and depressive symptoms , measured on the Burnam screening scale , at 3 years of follow-up . RESULTS In all patients , scores declined significantly over 3 years for physical function ( -3.8 ; P mental health ( -0.6 ; P = .05 ) , and energy/fatigue ( -3.8 ; P depressive symptoms were not significantly changed ( P = .20 ) . The effect of hormone therapy on these measures depended on the presence ( n = 434 ) or absence ( n = 2325 ) of flushing at study entry . Women with flushing who were assigned to hormone therapy had improved mental health ( + 2.6 vs - 0.5 ; P = .04 ) and fewer depressive symptoms ( -0.5 vs + 0.007 ; P = .01 ) over follow-up compared with those assigned to placebo . Women without flushing who were assigned to hormone therapy had greater declines in physical function ( -4.2 vs -3.3 ; P = .04 ) and energy/fatigue ( -4.6 vs -3.1 ; P = .03 ) over follow-up . Quality -of-life scores were significantly lower among patients with older age , diabetes , hypertension , chest pain , or heart failure . These differences in quality of life among women classified by clinical characteristics were much greater than the effects of hormone therapy . CONCLUSION Hormone therapy has mixed effects on quality of life among older women . The effects of hormone therapy depend on the presence of menopausal symptoms ; women without flushing had greater declines in physical measures , while women with flushing had improvements in emotional measures of quality of life", "BACKGROUND AND PURPOSE Observational studies have found that women who take estrogen after menopause are less likely to have a stroke than women who do not take estrogen . Although these findings indicate that estrogen may prevent stroke , an alternative explanation for the improved outcome of estrogen users is that they are healthier before starting therapy than nonusers . To test the therapeutic effect of estrogen with research methods that avoid this selection bias , we design ed a r and omized controlled trial . TRIAL DESIGN The Women 's Estrogen For Stroke Trial ( WEST ) is a double-blind , r and omized trial with a primary goal of determining whether 1 mg 17beta-estradiol daily , when compared with placebo , reduces the risk of recurrent stroke or death among postmenopausal women who have experienced a transient ischemic attack or nondisabling ischemic stroke . Exclusion criteria include use of estrogen at the time of stroke , breast or uterine cancer , inability to speak English , and estimated survival less than 5 years . Once r and omized , women remain under the care of their personal physicians for management of stroke risk factors . For early detection of endometrial hyperplasia and cancer , asymptomatic women receive medroxyprogesterone yearly ( 5 mg for 12 days ) and vaginal ultrasonography or biopsy at the end of the trial . Unscheduled uterine bleeding is evaluated with biopsy . A total of 652 women are sought at 20 hospitals in Connecticut and one in Massachusetts . CONCLUSIONS The WEST promises to provide critical guidance to women and their physicians regarding the effectiveness of estrogen in secondary stroke prevention", " 97 women aged 37 - 58 years who had undergone bilateral oophorectomy and hysterectomy and 45 women aged 34 - 53 years who had undergone hysterectomy only voluntarily participated in a therapeutic regime and follow-up visits . The oophorectomized women were r and omly divided into two groups ; one group received 20 - 40 mcg of mestranol per day and the other group received placebo ( no medication ) tablets . Total serum cholesterol measured by the method of Pearson Stern and McGanack serum triglycerides determined by the method of Van H and el and Zilversmit and blood sugar measured by st and ard Autoanalyzer techniques were performed . Fasting blood sample s were tested for every woman at her first visit and 40 oophorectomized women were re-tested after one year . Mean values for fasting blood sugars were in the range 50 - 110mg/100ml for both groups . Serum cholesterol rose significantly with age in women with intact ovaries . Oophorectomized women showed a significant rise in serum cholesterol at a younger age ( 43 years and under ) . Over age 46 there was no significant difference in serum cholesterol between these groups . The oophorectomized women showed a significantly slower rise of serum triglycerides with age than did the women with intact ovaries . In both groups serum triglycerides rose significantly with age . The oophorectomized women receiving mestranol showed a significant drop in serum cholesterol after one year and a significantly greater rise in serum triglycerides compared with the oophorectomized women receiving placebo treatment . No episodes of thromboembolism occurred in the mestranol-treated women", "OBJECTIVE To study the effects of postmenopausal hormone therapy ( PHT ) on the incidence and severity of rheumatoid arthritis ( RA ) . METHODS The Women 's Health Initiative r and omized controlled trials evaluated the effects of unopposed estrogen ( E-alone ) and estrogen plus progestin ( E+P ) compared with placebo on a diverse set of health outcomes over 7.1 and 5.6 years , respectively . RA cases were identified using historical and medication data . The hazard of developing RA was estimated using Cox proportional hazards regression models . Disease symptom severity was estimated using the Short Form 36 ( SF-36 ) and self-reported joint pain scores at baseline and after 1 year . Mean changes in severity were compared using linear regression models . RESULTS Of the 27,347 participants , 63 prevalent cases and 105 incident cases of RA were identified . A nonsignificant reduction in the risk of developing RA ( hazard ratio 0.74 ; 95 % confidence interval [ 95 % CI ] 0.51 , 1.10 ) was noted with PHT use . PHT use led to improved SF-36 scores in unadjusted analyses ( percent change 12.5 % ; 95 % CI -24.45 , -0.57 ) but not after adjustment for relevant covariates ( P = 0.33 ) . Nonsignificant improvements in joint pain scores were seen with PHT use ( odds ratio [ OR ] 4.10 ; 95 % CI 0.83 , 20.20 ) . PHT did not improve swelling ( OR 1.27 ; 95 % CI 0.08 , 19.63 ) or prevent new joint pains ( OR 0.72 ; 95 % CI 0.11 , 4.68 ) in RA participants . CONCLUSION There were no statistically significant differences in the risk of developing RA or the severity of RA between the PHT and placebo groups ", " Treatment of 63 oophorectomised women with oestrogen for five years prevented the reduction in bone mineral content observed in 57 women treated with a placebo preparation . When onset of therapy was delayed for three to six years there was a highly significant increase in bone mineral content mainly during the first three years of treatment . During the next two years there was no further increase in bone mineral , while the placebo-treated groups continued to lose bone at about 1 % per annum . In association with the changes in bone mass , the expected biochemical effects of oestrogen therapy also persisted for at least three years , and were compatible with a prolonged increase in parathyroid activity but a reduction in bone turnover", "CONTEXT Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function , but data from r and omized clinical trials have been sparse and inconclusive . The Women 's Health Initiative Memory Study ( WHIMS ) is an ancillary study of the Women 's Health Initiative ( WHI ) hormone therapy trials . On July 8 , 2002 , the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women . OBJECTIVE To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled clinical trial , WHIMS is an ancillary study of geographically diverse , community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995 . Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline , 4532 ( 92.6 % ) were enrolled in the estrogen plus progestin component of WHIMS . A total of 4381 participants ( 96.7 % ) provided at least 1 valid cognitive function score between June 1995 and July 8 , 2002 . INTERVENTIONS Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate ( n = 2145 ) or matching placebo ( n = 2236 ) . MAIN OUTCOME MEASURE Global cognitive function measured annually with the Modified Mini-Mental State Examination . RESULTS The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time ( mean follow-up of 4.2 years ) . Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo ( P = .03 ) , but these differences were not clinical ly important . Removing women by censoring them after adjudicated dementia , mild cognitive impairment , or stroke , and nonadherence to study protocol , did not alter the findings . Prior hormone therapy use and duration of prior use did not affect the interpretation of the results , nor did timing of prior hormone therapy initiation with respect to the final menstrual period . More women in the estrogen plus progestin group had a substantial and clinical ly important decline ( > or = 2 SDs ) in Modified Mini-Mental State Examination total score ( 6.7 % ) compared with the placebo group ( 4.8 % ) ( P = .008 ) . CONCLUSIONS Among postmenopausal women aged 65 years or older , estrogen plus progestin did not improve cognitive function when compared with placebo . While most women receiving estrogen plus progestin did not experience clinical ly relevant adverse effects on cognition compared with placebo , a small increased risk of clinical ly meaningful cognitive decline occurred in the estrogen plus progestin group", "CONTEXT In the Women 's Health Initiative trial of estrogen-plus-progestin therapy , women assigned to active treatment had fewer fractures . OBJECTIVE To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial ( September 1993-July 2002 ) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years . INTERVENTION Women were r and omly assigned to receive conjugated equine estrogen , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURES All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial ( July 7 , 2002 ) ; bone mineral density ( BMD ) , measured in a subset of women ( n = 1024 ) at baseline and years 1 and 3 ; and a global index , developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk . RESULTS Seven hundred thirty-three women ( 8.6 % ) in the estrogen-plus-progestin group and 896 women ( 11.1 % ) in the placebo group experienced a fracture ( hazard ratio [ HR ] , 0.76 ; 95 % confidence interval [ CI ] , 0.69 - 0.83 ) . The effect did not differ in women stratified by age , body mass index , smoking status , history of falls , personal and family history of fracture , total calcium intake , past use of hormone therapy , BMD , or summary fracture risk score . Total hip BMD increased 3.7 % after 3 years of treatment with estrogen plus progestin compared with 0.14 % in the placebo group ( P HR for the global index was similar across tertiles of the fracture risk scale ( lowest fracture risk tertile , HR , 1.20 ; 95 % CI , 0.93 - 1.58 ; middle tertile , HR , 1.23 ; 95 % CI , 1.04 - 1.46 ; highest tertile , HR , 1.03 ; 95 % CI , 0.88 - 1.24 ) ( P for interaction = .54 ) . CONCLUSIONS This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women . The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined . When considering the effects of hormone therapy on other important disease outcomes in a global model , there was no net benefit , even in women considered to be at high risk of fracture", "Objective To determine the effects of oral and transdermal hormone replacement therapy on lipid profile and hemostatic factors in postmenopausal women . Design Twenty subjects were treated with oral E2 valerate ( 2 mg ) combined with cyproterone acetate ( 1 mg ) ( group I ) and 21 with transdermal E2 ( 1.5 mg ) plus oral medroxyprogesterone acetate ( 5 mg ) ( group II ) . The effects on lipid profile and hemostatic parameters were evaluated at baseline and after 3 , 6 , and 12 months of treatment . Results Group I showed a stronger increase of high-density lipoprotein ( HDL ) cholesterol levels ( 2–8 % ) and stronger reduction of atherogenic indices ( total cholesterol/HDL cholesterol and low-density lipoprotein/HDL cholesterol ) than group II . Group II showed a more pronounced reduction of triglyceride ( 21–31 % ) and factor VII ( 6–10 % ) levels than group I. Both groups showed reduced concentrations of total cholesterol , low-density lipoprotein cholesterol , tissue plasminogen activator , plasminogen activator inhibitor-1 , antithrombin III , and protein S , whereas protein C was increased after 12 months of treatment . Conclusions The cardioprotective effects of hormone replacement therapy are demonstrated by favorable effects on lipid profile and fibrinolytic activity . Oral hormone replacement therapy showed a more prominent effect on lipoprotein metabolism than did transdermal administration , but transdermal medication had a stronger effect on triglyceride and coagulation factors . However , it needs to be considered that there is an increased risk of venous thrombotic events in the first year of treatment", "Data from the Third National Health and Nutrition Examination Survey ( 1 ) indicate that 11 % of U.S. women have a history of clinical gallbladder diseasethat is , either previous cholecystectomy or self-reported history of gallstones . Factors associated with gallbladder disease , at least in some studies , include older age , female sex , white ethnicity/race , obesity , rapid weight loss , and , among women , greater parity , use of oral estrogencontaining contraceptives , and postmenopausal estrogen therapy ( 2 ) . These associations , in general , have been based on observational data and may partly reflect the effects of ascertainment and recall bias , as well as confounding . While some observational studies suggest that estrogens increase the risk for gallbladder disease by as much as twofold to fourfold ( 3 ) , such an association has not been reported consistently ( 2 , 3 ) . The effect of combined estrogen plus progestin therapy has been less well studied , and no recent clinical trial data exist on the relation of such therapy to the risk for biliary tract surgery among postmenopausal women . To determine whether estrogen plus progestin therapy is associated with the risk for biliary tract surgery among postmenopausal women , we analyzed data from the Heart and Estrogen/progestin Replacement Study ( HERS ) , the first large r and omized , double-blind trial of estrogen plus progestin therapy for the secondary prevention of coronary heart disease ( 4 ) . Gallbladder disease events , including biliary tract surgery , were among several prespecified secondary outcomes of interest . Methods Participants Between 1 February 1993 and 1 October 1994 , 2763 postmenopausal women with coronary artery disease were recruited from 20 clinical centers across the United States for participation in HERS , a r and omized , double-blind study of the effect of combined , continuous estrogenprogestin therapy ( conjugated equine estrogens , 0.625 mg/d , and medroxyprogesterone acetate , 2.5 mg/d ) on recurrent coronary heart disease events . Baseline data , which were collected at the visits for initial screening and r and om allocation , included demographic characteristics , medical history , risk factors for coronary heart disease , physical examination , and laboratory data . Women were not eligible to enroll in HERS if they had used any estrogen or female hormones within the previous 3 months , including pills , suppositories , injections , vaginal creams , or transdermal patches . We excluded 510 women from these analyses who reported at enrollment a history of surgical gallbladder removal . We did include , however , 123 women with a self-reported history of gallstones who had not undergone cholecystectomy . After these exclusions , data from 2253 participants were available for analysis . Measurements Baseline data included participant age , years of education , number of pregnancies , ethnicity/race ( white , African American , or other ) , past use of postmenopausal estrogen therapy , history of cigarette smoking , history of alcohol consumption , and diabetes mellitus . Data were also obtained on use of lipid-lowering medications and antihypertensive medications , including thiazide diuretics . Participants who stated that they had smoked at least 100 cigarettes in their life were considered to have a history of smoking . Participants were asked , Has a doctor told you that you had diabetes , sugar diabetes , or high blood sugar ? Those who answered yes were classified as having a history of diabetes . Women with a history of gestational diabetes only were classified as not having diabetes mellitus . Participants were weighed without shoes or outdoor clothing on a st and ard balance-beam scale to the nearest 0.1 kg . Height was measured to the nearest 0.1 cm by using the height rod of a st and ard beam scale or , where available , a wall-mounted stadiometer . We calculated the body mass index as weight (kg)/height ( m2 ) . At baseline , year 1 , and the end of the study , serum lipid and lipoprotein levels were obtained from all participants and were measured at the Johns Hopkins Lipoprotein Analytical Laboratory , Baltimore , Maryl and , which is certified by the U.S. Centers for Disease Control and Prevention for the measurement of serum lipids and lipoproteins . Ascertainment of End Points Participants were determined to have incident gallbladder disease by physician adjudicators who were blinded to the r and omization status [ active hormone treatment or placebo ] . Symptomatic nonsurgical biliary tract disease was defined as a hospital admission for acute cholecystitis , choledocholithiasis , or gallstone pancreatitis and was established on the basis of 1 ) reported symptoms in combination with elevated levels on liver function testing and gallstones with dilated biliary ducts on abdominal ultrasonography or 2 ) nuclear medicine scan diagnostic of acute gallbladder disease . Incident biliary tract surgery , which included cholecystectomy , sphincterotomy , or bile duct exploration , was established by review of operative reports and discharge summaries . All biliary tract surgeries were cholecystectomies with the exception of 12 sphincterotomies and 2 stent insertions . Nonsurgical and surgical gallbladder disease events were considered separate end points and are mutually exclusive . The main HERS results , reported in 1998 ( 4 ) , were based on the near-final data available at that time . We present the up date d and final results for incident biliary tract events ( 5 ) . Statistical Analysis We used unpaired two-tailed t-tests to compare the age , level of education , number of pregnancies , body mass index , alcohol consumption , serum lipid level , and lipoprotein levels of the women r and omly assigned to receive postmenopausal hormone therapy or placebo . Using chi-square tests , we compared the hormone therapy and placebo groups according to ethnicity/race , history of lipid-lowering medication use , pre study postmenopausal estrogen use , thiazide diuretic use , cigarette smoking , ascorbic acid supplement use , history of gallbladder disease , and diabetes mellitus . The treatment groups were divided fairly equally with respect to baseline variables , except for statin use . To analyze the association between postmenopausal hormone therapy and incident gallbladder disease events , we used unadjusted and statin useadjusted proportional hazards models . All risk estimates were derived solely from proportional hazards models . We also estimated KaplanMeier curves for time to occurrence of biliary tract surgery , according to treatment assignment . The number of participants needed to be treated for a new case of biliary tract surgery to occur was calculated by using the incidence rates per person-year of observation . For predictor variables other than treatment assignment , we calculated the hazard ratio and 95 % CI by using proportional hazards regression models to estimate the risk for incident biliary tract surgery . We used simple regression models that controlled only for treatment assignment ; we also used multivariable regression models that included variables with a previously reported association with gallbladder disease . Our model-fitting methods relied primarily on biological criteria ; we began by including factors previously reported to be associated with gallbladder disease . Although the risk for type I errors is always present when c and i date predictors are many relative to the number of outcomes , our model-building process accounted for this possibility when we considered the statistical significance of the result ing multivariable model . Results were confirmed by using stepwise and backwards selection methods . We identified one statistically significant interaction between postmenopausal hormone treatment and smoking . Adjustment for this interaction did not substantially affect the hazard ratios for other variables entered in the multivariable models . We performed these analyses by using SAS software ( 6 ) . A correlation between outcomes at each clinical center could potentially affect the SEs for the relative hazard estimates . Therefore , to control for such potential clustering by center , we used STATA software ( 7 ) to generate robust SEs for the proportional hazards models ( 8) . Because site-specific practice patterns could confound the relation of statin use to biliary tract surgery , we also examined statistical models that included clinical center as a fixed effect . We calculated the number of participants needed to be treated to result in one additional biliary tract surgery by using the reciprocal of the absolute risk increase . However , because the 95 % CI for the absolute risk increase included zero , the CI for the number needed to treat for harm ( NNTH ) included . We use a method described by Altman ( 9 ) to present the CI in these circumstances . The CI around the NNTH will therefore range from an NNTH to to a number needed to treat for benefit ( NNTB ) . Role of the Funding Source Wyeth-Ayerst Research funded HERS . The study was design ed and carried out by the HERS investigators , including scientists from Wyeth-Ayerst Research . Investigators at the HERS Coordinating Center at the University of California , San Francisco , collected the outcome data , supervised the adjudication of outcome events , and analyzed the data . Results Gallbladder disease was particularly prevalent among this cohort of postmenopausal women with coronary artery disease . Twenty-three percent of women reported a history of cholelithiasis or cholecystectomy at baseline ( 10 ) . With the exception of statin use , which was more prevalent among women assigned to receive placebo ( P = 0.01 ) , the distribution of baseline variables was similar in both treatment groups ( Table 1 ) . Approximately 23 % of the HERS participants had a history of pre-enrollment hormone use ; the type and duration did not differ between the treatment groups . Table 1 . Selected Baseline Characteristics of Postmenopausal Women Receiving Hormone Therapy or Placebo in the Heart and Estrogen/progestin Replacement Study ( HERS ) A", "BACKGROUND Estrogen plus progestin therapy increases the risk for coronary heart disease ( CHD ) in postmenopausal women . However , this increased risk might be limited to the first years of use and to women who start therapy late in menopause . OBJECTIVE To estimate the effect of continuous estrogen plus progestin therapy on CHD risk over time and stratified by years since menopause . DESIGN Women 's Health Initiative r and omized , double-blinded , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00000611 ) SETTING 40 U.S. clinical centers . PATIENTS 16 608 postmenopausal women with an intact uterus at baseline from 1993 to 1998 . INTERVENTION Conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , or placebo . MEASUREMENTS Adherence-adjusted hazard ratios and CHD-free survival curves estimated through inverse probability weighting . RESULTS Compared with no use of hormone therapy , the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36 ( 95 % CI , 1.55 to 3.62 ) for the first 2 years and 1.69 ( CI , 0.98 to 2.89 ) for the first 8 years . For women within 10 years after menopause , the hazard ratios were 1.29 ( CI , 0.52 to 3.18 ) for the first 2 years and 0.64 ( CI , 0.21 to 1.99 ) for the first 8 years , and the CHD-free survival curves for continuous use and no use of estrogen plus progestin crossed at about 6 years ( CI , 2 years to 10 years ) . LIMITATION The analysis may not have fully adjusted for joint determinants of adherence and CHD risk . Sample sizes for some subgroup analyses were small . CONCLUSION No suggestion of a decreased risk for CHD was found within the first 2 years of estrogen plus progestin use , including in women who initiated therapy within 10 years after menopause . A possible cardioprotective effect in these women who initiated therapy closer to menopause became apparent only after 6 years of use . PRIMARY FUNDING SOURCE National Heart , Lung , and Blood Institute", "OBJECTIVE To describe self-reported cognitive changes in 875 postmenopausal women aged 45 - 64 years and assigned r and omly to hormone therapy ( either estrogen alone or estrogen in combination with a progestin ) . METHODS A 3-year placebo-controlled trial which included self-report data on problems with forgetfulness , concentration and distraction in groups of women assigned r and omly to placebo , estrogen alone or estrogen plus one of three progestin regimens . RESULTS Women assigned to any active treatment were consistently less likely to report cognitive symptoms than women assigned to placebo , but these results were not statistically significant . When compared with women assigned to estrogen plus any progestin , women assigned to estrogen alone had a significant increased risk for reporting problems with forgetfulness at follow-up ( odds ratio , OR = 1.47 ) . In the absence of problems with distraction at baseline , women assigned to estrogen alone were significantly less likely to report problems with distraction at follow-up , compared to women assigned to estrogen plus any progestin ( OR = 0.36 ) . Assignment to a continuous progestin regimen in combination with estrogen was marginally associated with an increased risk for reporting concentration problems at follow-up , compared to cyclic progestin regimens ( OR = 1.63 ) . CONCLUSIONS These results provide some evidence to support the hypothesis that estrogen improves memory , but findings are not statistically significant in this healthy middle-aged cohort . These data suggest that estrogen in combination with any progestin confers a decreased risk for reporting forgetfulness at follow-up , compared to estrogen alone . However , there is evidence that distraction problems reported at follow-up were side-effects of progestin . There is also some evidence that women administered progestins cyclically were at lower risk for reporting cognitive symptoms at follow-up , particularly concentration problems", "PURPOSE To determine if hormone therapy results in better cognitive function in older postmenopausal women . SUBJECTS AND METHODS The Heart and Estrogen/progestin Replacement Study ( HERS ) was a r and omized , placebo-controlled trial involving 2763 women with coronary disease . Women were assigned r and omly to conjugated estrogen ( 0.625 mg ) plus medroxyprogesterone acetate ( 2.5 mg ) in one tablet daily or identical placebo ; they were followed for a mean ( + /- SD ) of 4.2 + /- 0.4 years . Participants at 10 of the 20 HERS centers were invited to enroll in the cognitive function sub study . At the end of the trial , we measured cognitive function in 517 women in the hormone group and 546 in the placebo group using six st and ard tests : the modified Mini-Mental Status Examination , Verbal Fluency , Boston Naming , Word List Memory , Word List Recall , and Trails B. Cognitive function was not measured at baseline . RESULTS The mean age of participants at the time of cognitive function testing was 71 + /- 6 years . There were no differences in age-adjusted cognitive function test scores between the two treatment groups , except that women assigned to hormones scored worse on the Verbal Fluency test than women assigned to placebo ( 15.9 + /- 4.8 vs. 16.6 + /- 4.8 , P = 0.02 ) . Adjustment for other potential confounders and restriction of the analyses to women who had been adherent to study medication did not change the results . CONCLUSION Among older postmenopausal women with coronary disease , 4 years of treatment with postmenopausal hormone therapy did not result in better cognitive function as measured on six st and ardized tests . Whether these results also apply to elderly women without coronary disease can not be determined from this study", "Objective : To determine the extent to which the estrogen-induced changes in lipids and markers of carbohydrate metabolism explain the beneficial effect of estrogen therapy on the progression of carotid artery intima-media thickness ( IMT ) in postmenopausal women . Design : A r and omized , double-blind , placebo-controlled , single-center trial enrolling 222 postmenopausal women 45 years and older without cardiovascular disease and with low-density lipoprotein ( LDL ) cholesterol levels of 3.37 mmol/L or greater ( ≥130 mg/dL ) . Intervention was unopposed micronized 17β-estradiol versus placebo . Measurements were made using high-resolution B-mode ultrasonography to measure carotid artery IMT at baseline and every 6 months on-trial . Results : Progression of carotid IMT was inversely related to on-trial high-density lipoprotein ( HDL ) cholesterol ( P = 0.04 ) and was directly related to on-trial LDL-cholesterol ( P = 0.005 ) . Compared with placebo , women r and omized to estradiol showed a higher mean on-trial HDL-cholesterol level and a lower mean on-trial LDL-cholesterol level . In contrast , fasting glucose , insulin , and hemoglobin A1C were lowered and insulin sensitivity increased with estradiol therapy , but the changes were not related to carotid IMT progression . On-trial HDL-cholesterol and LDL-cholesterol were significant independent determinants of carotid IMT progression , jointly explaining 30 % of the treatment effect of unopposed estrogen on the progression of carotid IMT . Conclusion : Unopposed 17β-estradiol reduced carotid IMT progression in postmenopausal women in part by increasing HDL-cholesterol and decreasing LDL-cholesterol . Although women r and omized to estradiol showed improvement in all the markers of carbohydrate metabolism , these factors did not play a significant role in carotid IMT progression", "OBJECTIVE : To estimate the rates of endometrial hyperplasia , bleeding episodes , and interventions among menopausal women receiving unopposed oral estradiol or placebo therapy with ultrasound monitoring over 3 years . METHODS : Two-hundred eighteen healthy women with intact uteri enrolled in the Estrogen in the Prevention of Atherosclerosis Trial ( EPAT ) or the Women ’s Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial ( WELL-HART ) were r and omly assigned to either 1 mg of micronized 17&bgr;-estradiol ( n=96 ) or placebo ( n=122 ) daily for up to 3 years in a double-blind fashion . Patients were followed with annual measurement of endometrial thickness using transvaginal ultrasonography . Logistic regression was used to identify predictors of uterine bleeding and endometrial biopsy . RESULTS : Over the study periods , nine women ( 9.4 % of patients , 95 % confidence interval [ CI ] 3.6–15.2 % ) in the estradiol group developed hyperplasia . Eight of the nine cases ( 88.9 % ) of hyperplasia were simple without atypia . Women receiving estradiol were more likely than those receiving placebo to have at least one episode of uterine bleeding ( 67 % versus 11 % at 3 years , respectively , P estradiol group were also more likely to have an endometrial biopsy ( 48 % versus 4 % at 3 years , P estradiol , obesity ( body mass index [ BMI ] greater than 30 kg/m2 ) significantly increased the odds of uterine bleeding compared with normal-weight patients ( BMI 25 or less ) ( OR 3.7 , 95 % CI 1.2–11.8 ) . CONCLUSION : Short-term , unopposed estradiol therapy with gynecologic monitoring may be an option for the treatment of menopausal symptoms . Menopausal women choosing estradiol therapy , especially if obese , should anticipate uterine bleeding and the possibility of an endometrial biopsy . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT 00000559 and NCT 00115024 LEVEL OF EVIDENCE :", "OBJECTIVE To evaluate the effect of three different dosages of transdermally administered 17beta-estradiol on serum lipoproteins in women who had recently experienced surgical menopause . MATERIAL AND METHODS We undertook a 2-year , r and omized , double-blind , placebo-controlled study in which 126 subjects were recruited and stratified by age , and 93 patients completed the protocol . Serum lipoproteins were assessed before initiation of treatment and after 12 and 24 months of therapy with 0.025 , 0.05 , or 0.1 mg of estradiol daily . RESULTS Total serum cholesterol and low-density lipoprotein cholesterol showed dose-dependent decreases that reached statistical significance after 2 years of treatment with transdermally administered estradiol . CONCLUSION This study confirms that transdermally administered 17beta-estradiol has a modest beneficial effect on serum lipoproteins , with decreased levels of total cholesterol and low-density lipoprotein cholesterol", "OBJECTIVES To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin ( E+P ) in the Women 's Health Initiative ( WHI ) r and omized trial . METHODS Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI r and omized trial of E+P over an average 5.6 years of follow-up . RESULTS Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar . Duration of E+P use within the trial ( mean 4.4 years , S.D. 2.0 ) did not vary by prior use . Among 4311 prior users , the adjusted hazard ratio ( HR ) for E+P versus placebo was 1.96 ( 95 % confidence interval [ CI ] : 1.17 - 3.27 ) , significantly different ( p=0.03 ) from that among 12,297 never users ( HR 1.02 ; 95 % CI : 0.77 - 1.36 ) . The interaction between study arm and follow-up time was significant overall ( p=0.01 ) and among never users ( p=0.02 ) but not among prior users ( p=0.10 ) . The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users , and after about 5 years in women with no prior use . No interaction was found with duration ( p=0.08 ) or recency of prior use ( p=0.17 ) . Prior hormone use significantly increased the E+P hazard ratio for larger , more advanced tumors . CONCLUSION A safe interval for combined hormone use could not be reliably defined with these data . However , the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up , initially concentrated in women with prior hormone exposure , but with increasing risk over time in women without prior exposure , suggests that duration s only slightly longer than those in the WHI trial are associated with increased risk of breast cancer . Longer-term exposure and follow-up data are needed", "Background : To compare combined and sequential hormonal replacement therapies to each other as well as placebo in patients suffering from the postmenopausal syndrome . Clinical outcomes were measured concerning both the specific postmenopausal symptoms ( using the Kupperman scale ) and health or well-being dimensions ( using subscales of the General Health Question naire and specific depression and anxiety scales ) . Methods : A prospect i ve r and omized double-blind study over 12 months of 105 normal early postmenopausal women in the setting of a general hospital . Results : Both hormone replacement therapies were superior to placebo on the Kupperman scale ( sweating , hot flushing , myalgia and vertigo ) . The psychic symptoms on the Kupperman scale were psychometrically invalid . However , psychic symptoms as measured by the Beck Depression Inventory and the General Health Question naire were significantly improved by the hormonal replacement therapies . No differences were observed when combined therapy was compared to sequential therapy . Conclusion : One-year treatment with hormonal replacement therapy is superior to placebo in measuring the somatic and psychic symptoms of the menopausal syndrome . No differences were found in this respect between combined and sequential replacement therapy", "Background — Oral estrogen therapy increases the risk of venous thromboembolism ( VTE ) in postmenopausal women . Transdermal estrogen may be safer . However , currently available data have limited the ability to investigate the wide variety of types of progestogen . Methods and Results — We performed a multicenter case – control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France . We recruited 271 consecutive cases with a first documented episode of idiopathic VTE ( 208 hospital cases , 63 outpatient cases ) and 610 controls ( 426 hospital controls , 184 community controls ) matched for center , age , and admission date . After adjustment for potential confounding factors , odds ratios ( ORs ) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 ( 95 % CI , 1.5 to 11.6 ) and 0.9 ( 95 % CI , 0.4 to 2.1 ) , respectively . There was no significant association of VTE with micronized progesterone and pregnane derivatives ( OR , 0.7 ; 95 % CI , 0.3 to 1.9 and OR , 0.9 ; 95 % CI , 0.4 to 2.3 , respectively ) . In contrast , norpregnane derivatives were associated with a 4-fold-increased VTE risk ( OR , 3.9 ; 95 % CI , 1.5 to 10.0 ) . Conclusions — Oral but not transdermal estrogen is associated with an increased VTE risk . In addition , our data suggest that norpregnane derivatives may be thrombogenic , whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk . If confirmed , these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens", "Objective : To investigate the effects of hormone therapy on brain structure in a r and omized , double-blinded , placebo-controlled trial in recently postmenopausal women . Methods : Participants ( aged 42–56 years , within 5–36 months past menopause ) in the Kronos Early Estrogen Prevention Study were r and omized to ( 1 ) 0.45 mg/d oral conjugated equine estrogens ( CEE ) , ( 2 ) 50 μg/d transdermal 17β-estradiol , or ( 3 ) placebo pills and patch for 48 months . Oral progesterone ( 200 mg/d ) was given to active treatment groups for 12 days each month . MRI and cognitive testing were performed in a subset of participants at baseline , and at 18 , 36 , and 48 months of r and omization ( n = 95 ) . Changes in whole brain , ventricular , and white matter hyperintensity volumes , and in global cognitive function , were measured . Results : Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo ; however , the difference was significant only in the CEE group ( p = 0.01 ) . Rates of ventricular expansion correlated with rates of decrease in brain volume ( r = −0.58 ; p ≤ 0.001 ) and with rates of increase in white matter hyperintensity volume ( r = 0.27 ; p = 0.01 ) after adjusting for age . The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures . The change in global cognitive function was not different across the groups . Conclusions : Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance . Because the sample size was small and the follow-up limited to 4 years , the findings should be interpreted with caution and need confirmation . Classification of evidence : This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo", "CONTEXT The Women 's Health Initiative Estrogen-Alone Trial was stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the planned trial termination date . Postintervention health outcomes have not been reported . OBJECTIVE To examine health outcomes associated with r and omization to treatment with conjugated equine estrogens ( CEE ) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009 . DESIGN , SETTING , AND PARTICIPANTS The intervention phase was a double-blind , placebo-controlled , r and omized clinical trial of 0.625 mg/d of CEE compared with placebo in 10,739 US postmenopausal women aged 50 to 79 years with prior hysterectomy . Follow-up continued after the planned trial completion date among 7645 surviving participants ( 78 % ) who provided written consent . MAIN OUTCOME MEASURES The primary outcomes were coronary heart disease ( CHD ) and invasive breast cancer . A global index of risks and benefits included these primary outcomes plus stroke , pulmonary embolism , colorectal cancer , hip fracture , and death . RESULTS The postintervention risk ( annualized rate ) for CHD among women assigned to CEE was 0.64 % compared with 0.67 % in the placebo group ( hazard ratio [ HR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.75 - 1.25 ) , 0.26 % vs 0.34 % , respectively , for breast cancer ( HR , 0.75 ; 95 % CI , 0.51 - 1.09 ) , and 1.47 % vs 1.48 % , respectively , for total mortality ( HR , 1.00 ; 95 % CI , 0.84 - 1.18 ) . The risk of stroke was no longer elevated during the postintervention follow-up period and was 0.36 % among women receiving CEE compared with 0.41 % in the placebo group ( HR , 0.89 ; 95 % CI , 0.64 - 1.24 ) , the risk of deep vein thrombosis was lower at 0.17 % vs 0.27 % , respectively ( HR , 0.63 ; 95 % CI , 0.41 - 0.98 ) , and the risk of hip fracture did not differ significantly and was 0.36 % vs 0.28 % , respectively ( HR , 1.27 ; 95 % CI , 0.88 - 1.82 ) . Over the entire follow-up , lower breast cancer incidence in the CEE group persisted and was 0.27 % compared with 0.35 % in the placebo group ( HR , 0.77 ; 95 % CI , 0.62 - 0.95 ) . Health outcomes were more favorable for younger compared with older women for CHD ( P = .05 for interaction ) , total myocardial infa rct ion ( P = .007 for interaction ) , colorectal cancer ( P = .04 for interaction ) , total mortality ( P = .04 for interaction ) , and global index of chronic diseases ( P = .009 for interaction ) . CONCLUSIONS Among postmenopausal women with prior hysterectomy followed up for 10.7 years , CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD , deep vein thrombosis , stroke , hip fracture , colorectal cancer , or total mortality . A decreased risk of breast cancer persisted . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "BACKGROUND Estrogens stimulate proliferation of breast epithelium and may therefore increase the risk of benign proliferative breast disease , a condition that is associated with increased risk of breast cancer . We tested the effect of conjugated equine estrogen ( CEE ) on risk of benign proliferative breast disease in the Women 's Health Initiative ( WHI ) r and omized controlled trial . METHODS In the WHI CEE trial , 10,739 postmenopausal women were r and omly assigned to 0.625 mg/d of CEE or to placebo . Baseline and annual breast examinations and mammograms were required . We identified women in the trial who reported breast biopsies that were free of cancer , obtained the associated histological sections , and subjected them to st and ardized central review . Cox proportional hazards models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS A total of 232 incident cases of benign proliferative breast disease were ascertained during follow-up ( average duration , 6.9 years ) , with 155 in the CEE group and 77 in the placebo group . Use of CEE was associated with a more than two-fold increase in the risk of benign proliferative breast disease ( HR = 2.11 , 95 % CI = 1.58 to 2.81 ) . For benign proliferative breast disease without atypia , the HR was 2.34 ( 95 % CI = 1.71 to 3.20 ) , whereas for atypical hyperplasia , it was 1.12 ( 95 % CI = 0.53 to 2.40 ) . Risk varied little by levels of baseline characteristics . CONCLUSION Use of 0.625 mg/d of CEE was associated with a statistically significant increased risk of benign proliferative breast disease", "The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer . In contrast , no difference in the incidence of colorectal cancer was seen in the Women 's Health Initiative ( WHI ) r and omized , placebo‐controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow‐up of 13.2 years . This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology , grade , and stage of colorectal cancer , relevant subgroups , and deaths from and after colorectal cancer ", "BACKGROUND By contrast with many observational studies , women in the Women 's Health Initiative ( WHI ) trial who were r and omly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo . We aim ed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort . METHODS Between 1993 and 1998 , the WHI enrolled 10,739 postmenopausal women from 40 US clinical centres into a r and omised , double-masked , placebo-controlled trial . Women aged 50 - 79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were r and omly allocated by a computerised , permuted block algorithm , stratified by age group and centre , to receive oral conjugated equine oestrogen ( 0·625 mg per day ; n=5310 ) or matched placebo ( n=5429 ) . The trial intervention was terminated early on Feb 29 , 2004 , because of an adverse effect on stroke . Follow-up continued until planned termination ( March 31 , 2005 ) . Consent was sought for extended surveillance from the 9786 living participants in active follow-up , of whom 7645 agreed . Using data from this extended follow-up ( to Aug 14 , 2009 ) , we assessed long-term effects of oestrogen use on invasive breast cancer incidence , tumour characteristics , and mortality . We used Cox regression models to estimate hazard ratios ( HRs ) in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00000611 . FINDINGS After a median follow-up of 11·8 years ( IQR 9·1 - 12·9 ) , the use of oestrogen for a median of 5·9 years ( 2·5 - 7·3 ) was associated with lower incidence of invasive breast cancer ( 151 cases , 0·27 % per year ) compared with placebo ( 199 cases , 0·35 % per year ; HR 0·77 , 95 % CI 0·62 - 0·95 ; p=0·02 ) with no difference ( p=0·76 ) between intervention phase ( 0·79 , 0·61 - 1·02 ) and post-intervention phase effects ( 0·75 , 0·51 - 1·09 ) . In subgroup analyses , we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease ( p=0·01 ) or a family history of breast cancer ( p=0·02 ) . In the oestrogen group , fewer women died from breast cancer ( six deaths , 0·009 % per year ) compared with controls ( 16 deaths , 0·024 % per year ; HR 0·37 , 95 % CI 0·13 - 0·91 ; p=0·03 ) . Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis ( 30 deaths , 0·046 % per year ) than did controls ( 50 deaths , 0·076 % ; HR 0·62 , 95 % CI 0·39 - 0·97 ; p=0·04 ) . INTERPRETATION Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality . However , our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to population s at increased risk of such cancer . FUNDING US National Heart , Lung , and Blood Institute ; Wyeth", "UNLABELLED Abstract Background : It is estimated that 70 % of women in Western societies experience breast pain at least once during their lifetime . In the Women 's Health Initiative ( WHI ) , women treated with oral conjugated equine estrogen ( 0.625 mg ) with or without continuous oral medroxyprogesterone acetate ( 2.5 mg ) had a higher incidence of breast pain than those who received placebo . The effect of other hormone therapy regimens on breast pain is unknown . We compared breast pain among healthy , recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study ( KEEPS ) at Mayo Clinic . METHODS Women were r and omized to : 0.45 mg/day oral conjugated equine estrogen ( o-CEE ) plus 200 mg/day micronized progesterone ( m-P ) for the first 12 days of the month , 50 μg/day transdermal 17β estradiol ( t-E2 ) plus m-P for 12 days , or placebo pills and patch . Participants completed the Mayo Clinic breast pain question naire at baseline and yearly for the duration of the study . RESULTS Participants ( 116 ) averaged 53.0 years of age and 1.6 years past their last menses at baseline . At baseline , 12 women ( 10 % ) reported breast pain with an average worst pain score [ from 0 ( no pain ) to 10 ( worst pain ) ] of 0.39±1.28 . With treatment , the number of women reporting pain did not increase , and with either intention-to-treat or per- protocol analyses , breast pain scores did not differ significantly ( p=0.39 ) among groups : t-E2 ( 0.53±1.21 ) , o-CEE ( 0.32±0.78 ) , placebo ( 0.23±0.87 ) . CONCLUSION Four years of treatment with o-CEE at a lower dose than that studied in the WHI with cyclic m-P or transdermal E2 with cyclic m-P did not increase breast pain in healthy , recently menopausal women", "PURPOSE To assess the effects of adjuvant hormone therapy ( AHT ) on survival and disease outcome in women with epithelial ovarian cancer . PATIENTS AND METHODS Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer ( any International Federation of Gynecology and Obstetrics stage ) 9 or fewer months previously . Ineligible patients included those with deliberately preserved ovarian function , with a history of a hormone-dependent malignancy , or with any contraindications to hormone-replacement therapy . Patients were central ly r and omly assigned in a 1:1 ratio to either AHT for 5 years after r and om assignment or no AHT ( control ) . Main outcome measures were overall survival ( OS ) , defined as time from r and om assignment to death ( any cause ) , and relapse-free survival , defined as time from r and om assignment to relapse or death ( any cause ) . Patients who continued , alive and relapse free , were censored at their last known follow-up . RESULTS A total of 150 patients ( n = 75 , AHT ; n = 75 , control ) were r and omly assigned from 1990 to 1995 from 19 centers in the United Kingdom , Spain , and Hungary ; all patients were included in intention-to-treat analyses . The median follow-up in alive patients is currently 19.1 years . Of the 75 patients with AHT , 53 ( 71 % ) have died compared with 68 ( 91 % ) of 75 patients in the control group . OS was significantly improved in patients who were receiving AHT ( hazard ratio , 0.63 ; 95 % CI , 0.44 to 0.90 ; P = .011 ) . A similar effect was seen for relapse-free survival ( hazard ratio , 0.67 ; 95 % CI , 0.47 to 0.97 ; P = .032 ) . Effects remained after adjustment for known prognostic factors . CONCLUSION These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy , and this may , in fact , infer benefits in terms of OS in addition to known advantages in terms of quality of life " ]

[ "The aim of this study was to determine the effect of colloidal bismuth subcitrate ( De Nol ) on symptoms and gastric histology in patients with non-ulcer dyspepsia . In a single centre trial , patients with food related upper abdominal pain not caused by ulcer disease were r and omised to receive one tablet of colloidal bismuth subcitrate or matching placebo four times daily for eight weeks . Seventy three patients were entered and 51 completed the trial : 28 patients in the colloidal bismuth subcitrate group and 23 in the placebo group . Overall there was no difference between the two groups in terms of symptom relief . Among patients with histological gastritis ( n = 23 ) , however , those who took colloidal bismuth subcitrate used fewer antacid tablets ( for three of four fortnightly periods ) and were more likely to become asymptomatic ( eight of 11 v three of 12 , p less than 0.05 ) ; their gastritis was more likely to resolve ( five of 10 v 0 of 12 , p less than 0.025 ) and their gastric biopsies more likely to become negative for Helicobacter like organisms ( eight of nine v 0 of 12 , p less than 0.001 ) when compared with patients taking placebo . In contrast , patients who did not have gastritis in their index biopsies ( n = 28 ) fared similarly whether they received colloidal bismuth subcitrate or placebo . Our results indicate that the administration of colloidal bismuth subcitrate benefited non-ulcer dyspepsia patients with gastritis but had no effect on those without", "Background —Helicobacter pylori is a human pathogen that colonises the gastric mucosa and causes permanent gastric inflammation . Aims —To assess the symptoms of H pylori infection in an adult unselected population . Subjects — A r and om sample of 3589 adult Danes who were examined in 1982 and 1987 ( n=2987 ) . Methods —Abdominal symptoms within the preceding year were recorded at both attendances . Circulating IgG antibodies against H pylori in serum sample s drawn in 1982 were measured by using in-house indirect enzyme linked immunosorbent assays ( ELISA ) . Results —People with increased levels of IgG antibodies to H pylori were more likely than uninfected individuals to report heartburn ( odds ratio ( OR ) = 1.26 , 95 % confidence interval ( CI ) 1.03–1.54 ) and abdominal pain characterised by daily length ( OR = 1.33 , 95 % CI 0.92–1.91 ) , nocturnal occurrence ( OR = 1.62 , 95 % CI 1.19–2.19 ) , spring aggravation ( OR = 1.68 , 95 % CI 0.70–4.05 ) , and no relation to meals ( OR = 0.62 , 95 % CI 0.43–0.91 ) or stress ( OR = 0.69 , 95 % CI 0.50–0.95 ) . The inclusion of people with increased levels of IgG antibodies to H pylori , but without upper dyspepsia , at study entry significantly increased the likelihood of reporting upper dyspepsia at follow up ( OR = 1.71 , 95 % CI 1.24–2.36 ) . People with epigastric pain and increased levels of IgM antibodies to H pylori only indicative of acute H pylori infection were more likely to report nocturnal pain , heartburn , nausea , and vomiting . Conclusions —H pylori infection may precede the development of dyspepsia and is associated with a variety of gastrointestinal symptoms in people with no history of peptic ulcer disease", "This r and omised double blind placebo controlled study evaluated the effectiveness of colloidal bismuth subcitrate ( CBS ) , ampicillin and their combination in the treatment of Helicobacter Pylori in non-ulcer dyspepsia ( NUD ) and assessed if elimination of this organism is associated with improvement of gastritis and the symptoms . Forty-eight NUD patients with H. pylori and histologic gastritis were r and omly allocated to one of the three regimens for 28 days . Symptoms were assessed before and after treatment . Forty-three patients completed the trial . Repeat endoscopy within 48 hours of completing treatment showed suppression of H. pylori in 6 of 7 patients ( 85.7 % ) on combined therapy and one of 8 patients ( 12.5 % ) on CBS therapy ( p = 0.0205 ) . There was no suppression of the bacteria in patients treated with ampicillin . Repeat endoscopy performed 2 weeks after completing treatment showed suppression of H. pylori in 3 of 7 patients ( 42.9 % ) on combined therapy and none in the other two groups . Patients on combined therapy who had suppression of H. pylori , 48 hours or 2 weeks after completing treatment were noted to have historical improvement of their gastritis ( p = 0.0001 and p = 0.05 respectively ) . This was also associated with improvement of symptoms in these patients", "The aim of this study was to assess the effect of colloidal bismuth subcitrate ( CBS ) and metronidazole on Helicobacter pylori eradication and on the course of symptoms due to functional dyspepsia . Forty-one patients with functional dyspepsia were entered into the study and r and omized to treatment with CBS ( 120 mg four times a day ) for four weeks combined with metronidazole ( 250 mg four times a day ) for one week ( group A , N=21 ) or matching placebo ( group B , N=20 ) . The severity of gastritis and of bacterial colonization and the symptom score was assessed by endoscopy and clinical evaluation at baseline and after four , eight , and 24 weeks from the start of the treatment . With intent-to-treat analysis eradication was achieved in 16/25 ( 64 % ) patients in group A and in 6/24 ( 25 % ) in group B. At eight and 24 weeks the gastritis score was significantly lower only in those patients with eradication . No change was seen in patients in whom the bacteria was not eradicated . The symptom score at eight weeks was considerably lower both in patients with eradication and in those with infection . However , at 24 weeks a gradual decrease in the symptom score in patients with eradication and a worsening of symptoms in controls was observed . No differences were observed between patients with ulcerlike and those with dysmotility-like dyspepsia . The study confirms the need for a long observation period after antibacterial treatment in patients with functional dyspepsia and suggests thatHelicobacter pylori-eradicating treatment improves the course of this functional syndrome", "Gastritis caused byHelicobacter pylori ( HP ) is common in patients with nonulcer dyspepsia ( NUD ) , but an etiologic relationship between the histologic lesion and clinical symptoms is unproven . HP is inhibited by bismuth subsalicylate ( BSS ) , a traditional remedy for dyspeptic complaints . The aim of this study was to assess the short- and long-term effects of BSS on HP , gastritis , and symptoms in patients with NUD . One hundred twenty-six patients with NUD who were shown to be infected withH. pylori ( HP+ ) were enrolled . There was a two-week placebo run-in period to eliminate placebo responders . Fifty patients remained symptomatic and were r and omly assigned to therapy with either BSS liquid or a matching placebo . EGD , biopsy , and clinical evaluations were performed at entry , at week 5 ( end of therapy ) , at week 9 ( four weeks after therapy ) , or at time of symptomatic relapse . Twenty-seven patients received placebo and 23 patients received BSS . BSS suppressedH. pylori in 15/23 patients ( 65 % ) and eradicated it in one patient , whereas the placebo had no effect onH. pylori . Gastritis improved during therapy with BSS but relapsed by week 9 . There was no significant change in level of dyspeptic symptoms during or after treatment , although one month after the end of treatment , the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured . The study confirms that BSS given for three weeks suppresses but does not usually eradicateH. pylori . Such short-term suppression ofH. pylori heals gastritis but does not result in clinical improvement", "Infection with Helicobacter pylori probably increases the risk for developing duodenal and gastric ulcer disease . Previous studies have shown that 75 % to 100 % of patients with duodenal ulcer and 35 % to 86 % of patients with gastric ulcer have evidence of an H. pylori infection [ 1 ] . The finding that eradication of H. pylori in patients with duodenal ulcer is associated with a statistically significant decrease in the recurrence rate of the disease further supports the association [ 2 - 5 ] . However , these observations may just reflect the frequent coexistence of duodenal ulcer with antral gastritis [ 6 ] , which has been shown to be caused by H. pylori [ 7 , 8 ] . Wormsley [ 9 ] has noted that the Henle-Koch postulates have not been satisfied for causation of duodenal ulcer by H. pylori because the organism has not been shown to produce the disease . The evidence is weaker that H. pylori causes gastric ulcer because only a single study with 26 patients has shown that antimicrobial therapy directed against H. pylori decreased the gastric ulcer recurrence rate [ 5 ] . None of the previous studies evaluated patients with duodenal or gastric ulcers before they were diagnosed or hospitalized with their disease . The usual temporal sequence is that patients with peptic ulcer disease are examined to detect H. pylori infection at the time the diagnosis is made or after they have had treatment to eradicate the organism . Consequently , peptic ulceration could possibly predispose persons to colonization by H. pylori [ 9 ] . We did a prospect i ve study in a large population -based cohort using serum specimens that were obtained from study participants before they were diagnosed with peptic ulcer . We tried to determine whether H. pylori infection , as shown by the presence of specific IgG antibodies , is a risk factor for the subsequent development of either duodenal or gastric ulceration . Methods Study Population Japanese-American men born from 1900 to 1919 , who were identified by the Honolulu Heart Program in 1965 by using the comprehensive 1942 Selective Service draft registration files [ 10 ] , composed the study population . Of 11 148 eligible men , 8006 ( 72 % ) were interviewed and examined from 1965 to 1968 , 180 ( 2 % ) died before they could be examined , and 2962 ( 26 % ) did not participate in the program . Study participants ranged in age from 45 to 68 years . The data collected included birthplace , marital status , history of alcohol use , blood pressure , and body mass index ( the weight in kilograms divided by the square of the height in meters ) . Serum cholesterol values were determined by the Auto Analyzer N-24A method , and serum glucose values were determined by the Auto Analyzer N-2B method 1 hour after a 50-g glucose load had been given [ 11 ] . A total of 7498 ( 94 % ) men returned for a second examination between 1967 and 1970 , and a serum specimen was obtained at this time . Serum specimens for a 20 % r and om sample of the men were sent to the U.S. Public Health Service Hospital in San Francisco , whereas specimens for the remaining 5924 men were stored at 20C at the study site . Four hundred eighty-one patients with previous gastrectomy or a previous diagnosis of peptic ulcer disease were excluded from the study . The average age of the remaining 5443 patients at the time of their second examination was 56.6 years . Surveillance Methods Surveillance of the cohort to identify incident patients with peptic ulcer was done by a continuous review of discharge records of all general hospitals on Oahu . Based on a 19-year follow-up survey of the study patients from the time of their examination in 1965 to 1968 , only 1.3 % of the men could not be located on Oahu . Thus , surveillance was nearly complete . Two hundred fifty-eight patients were hospitalized with peptic ulcer disease from 1968 to 1989 . One hundred sixty ( 62 % ) patients had their diagnosis confirmed by examination of tissue obtained by either surgery or biopsy , 36 ( 14 % ) were diagnosed by radiologic examination , and 62 ( 24 % ) were clinical ly diagnosed based on the endoscopic or surgical report of the presence of an ulcer . One hundred sixty-nine incident patients had gastric ulcer , 73 had duodenal ulcer , and 16 had gastric and duodenal ulcers . Seventeen of the 169 patients with gastric ulcer , 6 of the 73 patients with duodenal ulcer , and 2 of the 16 patients with gastric and duodenal ulcers were removed from study because they had an insufficient amount of serum in the freezer repository . Selection of Controls Each of the remaining patients was matched with one control from the study cohort based on age at examination ( 47 to 70 years ) and date of serum collection . If a potential control had a diagnosis of gastric cancer before or after the serum was obtained , he was excluded from the study . As a consequence , 160 patients ( 3.1 % ) were removed from the control pool of 5185 men because of the reported association between H. pylori infection and gastric cancer [ 12 , 13 ] . Of the remaining 5025 men , 336 ( 6.7 % ) were excluded because they previously had cardiovascular disease or other cancer , and 1532 ( 30.5 % ) were excluded because they were diagnosed with cardiovascular disease or other cancer after their serum collection . This exclusion was done because the serum specimens from these patients are going to be used for other studies . A total of 3157 patients remained in the pool of controls from which 233 ( 7.4 % ) were matched to incident case- patients with peptic ulcer . Each control participant was alive at the time of hospitalization of the matched case-patient , so that death was not a competing factor . Serologic Testing The presence of serum IgG antibodies to H. pylori was determined by enzyme-linked immunosorbent assay ( ELISA ) , using the Pyloristat kit ( Whittaker Bioproducts , Inc. , Walkersville , Maryl and ) . As vali date d by the manufacturer , the results of this assay closely mirror those of a previously described IgG ELISA [ 13 - 18 ] . In brief , serum specimens from patients were diluted 1:20 for use in the kit , and IgG levels of sera were determined according to the manufacturer 's instructions . The serum specimens were coded so that the laboratory technician could not distinguish case- patients from controls . A ratio of 1.00 or greater was considered positive , a ratio of less than 0.80 was considered negative , and a ratio of 0.80 to 0.99 was considered equivocal , as calibrated in the kit . Two patients with gastric ulcer and two patients with duodenal ulcer or their controls had equivocal values , so they were excluded from the study . Statistical Analysis A matched casecontrol study design was used to identify the patients and controls for serum tests . As a result , odds ratios , based on the results of the H. pylori IgG antibody test , were determined using conditional logistic regression methods [ 19 ] . When odds ratios were indeterminable , approximate confidence intervals ( CIs ) were determined by the method of Breslow and Day [ 19 ] . Tests for trend in the logit of risk were derived from conditional logistic regression models by using grouped H. pylori test results ( coded as 1 , 2 , 3 , and 4 ) . All conditional logistic regression models were fitted using iterative maximum likelihood methods and a special application of the proportional hazards regression model [ 20 ] . Results The characteristics of the 229 patients with peptic ulcer and of their matched controls are presented in Table 1 . The two groups of men were similar with respect to demographic characteristics and laboratory values . Table 1 . Characteristics of Patients with Peptic Ulcer and of Controls The mean age at diagnosis was 67.5 years ( range , 52.7 to 87.2 years ) for the 150 patients with gastric ulcer , 64.5 years ( 49.4 to 80.0 years ) for the 65 patients with duodenal ulcer , and 63.5 years ( 52.4 to 83.1 years ) for the 14 patients with gastric and duodenal ulcers . Table 2 shows the association between the H. pylori test result and peptic ulcer by specific type . Ninety-three percent ( 139 of 150 ) of the patients with gastric ulcer and 78 % ( 117 of 150 ) of the matched controls had a positive H. pylori-specific IgG antibody level , yielding an odds ratio of 3.2 ( P = 0.001 ) . ( The odds ratio is determined by dividing 32 pairs by 10 -/+ pairs . ) Ninety-two percent of the case- patients with duodenal ulcer and 78 % of the matched controls had a positive test result , yielding an odds ratio of 4.0 ( P = 0.03 ) . If a patient had either a gastric or duodenal ulcer , then the odds ratio was 3.4 ( P = 0.0001 ) . Only 14 patients had both gastric and duodenal ulcers . The odds ratio was 1.3 ( P > 0.2 ) , based on these patients . Table 2 . Odds Ratio for the Association between Helicobacter pylori Seropositivity and Type of Peptic Ulcer Because some of the hospitalized patients with peptic ulcer may have developed their ulcers after the use of adrenocorticosteroids or nonsteroidal anti-inflammatory drugs , we systematic ally review ed the hospital records of the patients . A similar review could not be done for the controls because they were not hospitalized . We found that 18 of the 150 patients with gastric ulcer and 9 of the 65 patients with duodenal ulcer had taken these medications at the time of hospitalization . If these patients and their matched controls were excluded , the odds ratio would have been 3.3 ( 95 % CI , 1.6 to 7.0 ) for gastric ulcer , 3.3 ( CI , 0.9 to 12.1 ) for duodenal ulcer , and 3.3 ( CI , 1.7 to 6.4 ) for either gastric or duodenal ulcer . Of the 215 patients with either gastric or duodenal ulcer , 100 also had a hospital-based diagnosis of cardiovascular disease or cancer . If these patients were excluded from the study , as were controls with these diseases , 115 patients with gastric or duodenal ulcer would have remained in the study . Ninety-four percent of these case- patients and 77 % of their controls had a positive test result for H. pylori antibody . The odds ratio for peptic ulcer was 4.3 ( CI , 1.8 to 10.5 ) in this group of patients . When the patients with gastric ulcer who had positive antibody", "Non-ulcer dyspepsia ( NUD ) is a common complaint in which no systematic illness or organic proximal alimentary tract disease can be identified . The pathophysiology of NUD is probably heterogeneous . Eighty-two subjects with NUD were studied in a prospect i ve r and omized placebo-controlled study to assess the efficacy of colloidal bismuth subcitrate ( CBS ) chewable tablets at a dose of four tablets daily for 1 month . The role of Campylobacter pylori and associated histological gastritis was evaluated . Sixty-one percent of NUD patients had C. pylori in the gastric antrum compared with 25 % of age-matched controls . C. pylori was associated with acute and chronic inflammation ( P less than 0.001 ) in the antrum . C. pylori was cleared in 59 % of CBS-treated subjects compared with only 4 % placebo ( P less than 0.05 ) . Both acute and chronic inflammation improved in subjects cleared of bacteria . Clearance of C. pylori and histological improvement was associated with a significant decrease in symptoms . In C. pylori negative subjects improvement in symptoms occurred in both the placebo and active treatment groups . This study would suggest that C. pylori and associated histological gastritis may play a role in non-ulcer dyspepsia", "OBJECTIVE To ascertain whether triple therapy alters the history of Helicobacter pylori (HP)-related nonulcer dyspepsia ( NUD ) . METHODS Forty-one young ( by serology , rapid urease test , and antral biopsy . Endoscopy excluded the presence of ulcer . These cases were r and omly plotted into control ( n = 21 ) and triple therapy ( n = 20 ) groups . In the former group , H2 blocker was given for 2 months and then intermittent antisecretory agents for up to 1 yr . In the latter group , 20 patients received a course of triple therapy and then were treated like the control group . The symptom scores ( range : 0 - 10 ) were collected on enrollment , and at the end of 2nd , 6th , and 12th months . Each case had serial tests of HP IgG ELISA titer on start , at weeks 2 , 4 , and 8 , at the 6th month , and at the end of the 1st yr . The second endoscopy was done in the 9th wk for eradication survey , and the third endoscopy , at the end of the 1st yr to resurvey the HP status . The histological gradings of biopsy specimens , sample d on each endoscopy , were compared . RESULTS In the triple therapy group , the rate of eradication of HP was 75 % . At he end of the 2nd month , the HP-eradicated cases of the triple therapy group improved the symptom score more significantly then the noneradicated cases ( 2.42+/-1.37 vs.4.76+/-1.58 , p symptom scores of the eradicated cases improved more significantly than those of the control group ( 6th month , 0.61+/-1.18 vs. ] 2.66+/-2.06 ; 1st yr , 0.82+/-1.17 vs. ] 3.56+/-2.89 , p ELISA titers occurred only in eradicated cases and became significantly evident from the 4th wk ( 0.30+/-0.15 vs. ] 0.49+/-0.07 , p acute and chronic pathological grading was improved in the triple group at the end of the 1st yr ( acute , 1.95 - 0.46 ; chronic , 1.9 - 0.92 ; p control therapy at 1 yr , triple therapy showed greater symptomatic , serological , and histological improvements . Therefore , triple therapy is beneficial to symptomatic HP-related NUD", "We evaluated clindamycin and bismuth subsalicylate ( Pepto-Bismol ) for treatment of Helicobacter pylori infection . Patients with culture or histology positive for H. pylori were r and omized to receive two tablets of bismuth subsalicylate four times daily for 4 weeks or bismuth combined with 2 weeks of 300 mg clindamycin four times daily . Clinical symptoms were recorded before and after treatment by means of visual analog scales . Patients in both treatment arms showed improvement in clinical scores for abdominal pain , heartburn , and gas or bloating . Microbiologic cure was achieved in only 1 of 11 patients treated with bismuth alone and in none of 7 treated with bismuth/clindamycin . Successful eradication of H. pylori may require combination of multiple antibiotics , as recommended at the IXth World Congress of Gastroenterology , or pharmacokinetic modulators such as H2-blockers or omeprazole", "An investigator blind trial was performed comparing bismuth salicylate , erythromycin ethylsuccinate , and placebo in the treatment of Campylobacter pyloridis associated gastritis in patients without peptic ulceration . Fifty patients fulfilled the study criteria . There was a strong correlation between the presence of C pyloridis and histologically confirmed gastritis . Clearance of organisms led to improvement of the gastritis . C pyloridis was cleared from 15 patients ; of these , 13 had gastritis initially , which resolved in 12 . Conversely , gastritis resolved in only four of 32 patients not cleared of organisms ( p less than 0.0001 ) . There was significantly greater improvement in endoscopic appearances in the patients cleared of C pyloridis compared with those whose infection persisted ( p less than 0.001 ) . In the three treatment groups organisms were cleared from 14 of 18 patients receiving the locally active bismuth salicylate , only one of 15 patients receiving erythromycin ethylsuccinate , and none of 17 patients taking placebo . These findings suggest that the ideal antimicrobial for the successful eradication of C pyloridis associated gastritis should be locally active , stable at low pH , and should penetrate gastric mucus . The resolution of gastritis and improvement in endoscopic appearances associated with clearance of C pyloridis support the view that these organisms may play a part in this condition", "We conducted a double-blind , placebo-controlled , r and omized treatment study in Peruvian adults with antral gastritis associated with Campylobacter pylori . Patients received either 400 mg of furazolidone ( n = 14 ) , 400 mg of nitrofurantoin ( n = 24 ) , or a placebo ( n = 31 ) for 14 days . Endoscopy was carried out at baseline , 1 day after ceasing therapy , and 6 wk after the end of treatment to verify colonization by C. pylori and determine the extent of gastric inflammation . Treatment with nitrofurantoin or furazolidone markedly reduced or , in some cases , cleared C. pylori from the antrum ( p less than 0.0005 compared with placebo ) . Resolution of acute gastric inflammation , as evidence d by decreased polymorphonuclear leukocyte infiltration and regeneration of the mucus layer , paralleled the reduction in bacterial colonization ( p less than 0.005 compared with placebo ) . A high percentage of patients experienced relapse ( recolonization by C. pylori and return to pretreatment levels of gastritis ) within 6 wk after cessation of treatment . Significant relief of dyspeptic symptoms was not evident during the study", "BACKGROUND A contribution of Helicobacter pylori gastritis to the pathogenesis of non-ulcer dyspepsia ( NUD ) remains uncertain . METHODS Administration of an appropriate clinical question naire followed by endoscopy allowed us to select , among 139 out patients with dyspepsia , 87 non-ulcer dyspepsia patients with more severe and group-distinctive symptoms , 35 of whom were classified as having ulcer-like ( ULD ) . 38 as dysmotility-like ( DLD ) , and 14 as reflux-like dyspepsia ( RLD ) . Biopsy specimens were evaluated for H. pylori gastritis in accordance with the Sydney system . The 70 H. pylori-positive cases were treated with omeprazole , 20 mg twice daily , and amoxycillin , 1 g three times daily for 2 weeks . RESULTS Higher rates of H. pylori colonization were found histologically in the gastric mucosa of ULD ( 91 % ) and RLD ( 86 % ) than in that of DLD ( 68 % ) or asymptomatic ( 42 % ) patients . ULD differed from RLD patients in their higher score of antritis activity . Three and 6 months after H. pylori eradication ULD ( but not DLD ) showed significant regression of dypspetic symptoms scores . CONCLUSIONS It seems likely that H. pylori gastritis , with special reference to active antritis , is among causative factors of ULD . Its role in the pathogenesis of RLD and DLD needs further investigation", "Summary The presence ofCampylobacter pylori was investigated in biopsy specimens obtained during gastrofiberscopy from 103 consecutive patients prospect ively . Patients included 25 with gastric ulcer , 4 with duodenal ulcer , 5 with coexisting gastroduodenal ulcer , 31 with gastroduodenal ulcer with gastritis , 27 with gastritis , 3 with gastric polyps and 8 with gastric cancer . Results were compared with 20 healthy control subjects who were endoscopically normal . Two specimens each were taken from 3 sites in the stomach . One part was used for a histological study to examine the presence of the organisms . The other part was cultured using Skirrow ’s agar microaerophilically . Conventional microflora and C. pylori were examined in gastric contents of some cases . Bacteriological features of isolated strains of C.pylori were identical to the NCTC strain . C.pylori was the most dominant organism in gastric contents at any pH level . Detection rates of C.pylori by bacteriological culture were 96 % in gastric ulcer , 100 % in duodenal ulcer , 80 % in coexisting gastroduodenal ulcer , 84 % in gastroduodenal ulcer with gastritis , 70 % in gastritis , 100 % in gastric polyps and 100 % in gastric cancer , and the percentages recognized by histological studies were 81,100,100 , 84 , 71 , 67 , and 57 % , respectively . The values in healthy controls were 55 % by histological and bacteriological methods ( P<0.001 compared with overall ulcer patients ) . These results supported the close association between C.pylori and gastroduodenal diseases", "There seems to be a worldwide geographic variation in the prevalence of peptic ulcer disease , although there are few reliable population based studies . This study aim ed to determine the prevalence of peptic ulcer disease in a community in southern India and to evaluate the relationship between dyspeptic symptoms , Helicobacter pylori infection , gastritis , and peptic ulcer disease . A sample population was selected r and omly from a rural monastic settlement in southern India . Subjects were interviewed using a st and ardised symptom and demography question naire then underwent upper endoscopy and antral biopsy for histology and CLO rapid urease test . Altogether 197 subjects from a population of 1499 ( 13.1 % ) were studied . All were male monks and ethnically Tibetan . The median age was 28 years ( range : 21 - 81 ) . None smoked or took NSAIDs . The six month period prevalence of dyspeptic symptoms was 68.5 % . Current symptoms were present in 58.9 % of subjects . Dyspepsia was more common in subjects aged 40 years or younger ( p H pylori was detected in 77.2 % subjects . There was no association between dyspepsia and the presence of H pylori or histological gastritis , although there was a strong correlation between symptoms and ulcer ( p active peptic ulcer was 6.6 % ( 13/197 ) . All ulcers detected were either prepyloric or pyloroduodenal in location . A further 6.6 % of subjects had definite evidence of scarring or deformity indicative of ulceration in the past . Subjects with past or present ulcers comprised 17.8 % of dyspeptic subjects . H pylori was present in all subjects with active ulcers and in 12/13 of those with scarring . Dyspepsia , H pylori infection , gastritis , and peptic ulcer are all more common in this population than in those from developed countries . Ulcer disease , however , accounts for only a small proportion of subjects with symptoms and neither H pylori infection nor gastritis are significantly associated with the presence of dyspepsia", "BACKGROUND The role of Helicobacter pylori in functional dyspepsia is unclear . The aim of this population -based study was to determine whether the prevalence of H. pylori infection is higher among people with dyspepsia or irritable bowel syndrome ( IBS ) than among symptomless persons after control for age , sex , and socioeconomic status . METHODS In a postal question naire we asked a representative sample ( 20 - 79 years ; n = 1260 ) from a Swedish municipality about abdominal symptoms in the preceding 3 months . A r and omly selected sub sample , 50 with dyspepsia , 50 with IBS , and 50 symptomless , matched with regard to age , sex , and education , were tested for the presence of IgG antibodies to H. pylori , using the HM-CAP immunoassay . RESULTS Fifty-five persons ( 38 % ) were H. pylori-seropositive . The seroprevalence among dyspeptics ( 33 % ) did not exceed that in healthy people ( 48 % ) or in those reporting IBS ( 33 % ) . The prevalence increased with age and with lower social class , but the latter association disappeared when age was taken into account . Neither sex nor symptom intensity predicted Helicobacter seropositivity . CONCLUSION Our data are incompatible with an important aetiologic role for H. pylori in functional dyspepsia", "Non-ulcer dyspepsia ( NUD ) is a poorly understood syndrome often present in association with gastritis . Among patients undergoing gastroscopy , some with NUD have a gastric mucosa colonized by the campylobacter-like organism , Campylobacter pylori . We therefore studied prospect ively 55 consecutive patients with NUD and 15 normal controls to determine the prevalence of C. pylori organisms , and to investigate their association with histological gastritis , macroscopic evidence of gastritis , sex , smoking , alcohol consumption , and dyspeptic symptoms . We found a 45.4 % prevalence in NUD patients which was statistically significantly higher than the 13.33 % prevalence in the control group ( p less than 0.05 ) . We also found a close association between C. pylori and microscopic evidence of gastritis ( p less than 0.001 ) , male sex ( p less than 0.001 ) , and postpr and ial bloating ( p less than 0.05 ) . We did not find any significant association between C. pylori and macroscopic evidence of gastritis , smoking , alcohol consumption and other dyspeptic symptoms . Our findings suggest that C. pylori may play a pathogenic role in NUD", "A study was undertaken to determine the role of Helicobacter pylori in non-ulcer dyspepsia ( NUD ) and to determine the efficacy of colloidal bismuth subcitrate ( CBS ) in the treatment of NUD . Seventy-one patients were r and omly allocated ( double blind ) to CBS or placebo , two tablets twice daily for 4 weeks . The severity of dyspepsia was scored and endoscopies performed before and after treatment , and antral biopsy specimens were taken for bacteriologic and histologic examination . Forty patients had H. pylori infection , and all had changes of chronic active gastritis . H. pylori was cleared from 17 to 21 patients ( 81 % ) treated with CBS , whereas none of the 19 patients treated with placebo cleared the bacteria . Improvement in histology was noted in 15 of 21 patients ( 71.4 % ) treated with CBS , whereas no improvement was noted in any of the placebo controls . Thirty-one patients were negative for H. pylori . All had either normal gastric histology or minor degrees of inflammation . Seventeen of these patients received CBS , and 14 received placebo . All groups reported improvement in the symptom score ; however , the H. pylori-positive , CBS-treated group recorded a significantly higher improvement than the other groups ( p less than 0.001 ) . Relapse of H. pylori infection after initial clearance of the bacteria was high . Twelve of 16 patients evaluated relapsed 1 month after withdrawal of CBS", "BACKGROUND The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is controversial . METHODS In a prospect i ve , long-term , double-blind study we r and omized 100 patients with non-ulcer dyspepsia and H. pylori infection to receive either of two treatment regimens : 1 ) bismuth-based triple therapy ( n = 50 ) or 2 ) bismuth + placebo ( n = 50 ) . RESULTS Triple therapy : subjects who became H. pylori-negative ( n = 42 ) showed a significant symptomatic response when interviewed at 8 weeks , 6 months , and 1 year ( P no decrease in symptoms at 8 weeks , 6 months , and 1 year . Bismuth-placebo therapy : subjects who became H. pylori-negative ( n = 7 ) showed an improvement in symptoms at 8 weeks , 6 months , and 1 year . Those who continued to harbour the infection after treatment ( n = 42 ) showed an insignificant improvement in the motility and non-specific groups only . CONCLUSION This study shows that eradication of H. pylori results in a significant long-term reduction in symptoms of non-ulcer dyspepsia", "Fifty-three patients with previously uninvestigated chronic dyspepsia symptoms in the absence of gastrointestinal or extra-gastrointestinal disease ( functional dyspepsia ) underwent antral and duodenal mucosal biopsies to detect the role of such samplings in the presence of normal endoscopic findings . Patients were enrolled in a r and omized , placebo-controlled , double-blind trial , receiving either eradicating treatment ( colloidal bismuth subcitrate plus metronidazole ) or placebo if they had Helicobacter pylori-associated gastritis ( 20 patients ) , or cisapride or placebo if they had normal antral mucosa ( 28 cases ) . Unsuspected celiac sprue was found in one patient . Eradicating treatment ameliorated histological gastritis ( p = 0.01 ) . However , owing to great placebo efficacy , symptom remission rates following a 1-month wash-out period in both treatment groups were no higher than that in controls . Independent of the initial r and omization , an extremely low symptom recurrence rate was observed during a drug-free follow-up study equivalent to the mean duration of symptoms before enrollment . We conclude that in functional dyspepsia , bulbar and antral biopsies are not useful in clinical management , equivalent symptom relief can be achieved in patients r and omly assigned to both drugs and placebos , and such improvement can be long lasting in the absence of any maintenance treatment . We believe the prevalence of unsuspected villous atrophy and the therapeutic role of investigation-based reassurance deserve further assessment", "OBJECTIVE The aim was to explore the effect of eradication therapy on dyspeptic symptoms in patients with known peptic ulcer disease ( PUD ) . METHOD A total of 164 known dyspeptics and 147 non-dyspeptic attenders at six UK general practice s were recruited . The Helisal Rapid Blood test was performed in the practice s and eradication therapy left to the preference of the general practitioner . Patients were followed prospect ively by a Likert scaled symptom question naire and record review . The symptom question naire distinguished between patients known to have dyspepsia and those not . RESULTS There was a statistically significant decrease in dyspeptic symptoms in patients with known PUD who received eradication therapy ( n = 43 , Z = -2.63 , P = 0.009 ) . CONCLUSIONS Eradication of Helicobacter pylori in primary care can lead to a reduction in consumption of H2 receptor antagonists and hence cost savings . This study demonstrates that dyspeptic symptoms also decrease . The question naire could be used in further studies to evaluate the effect of management on dyspeptic symptoms in the primary care setting", "BACKGROUND & AIMS Multiple tests are available for determining Helicobacter pylori infection . Our aim was to compare the sensitivity , specificity , and negative and positive predictive value of the most widely available tests for diagnosis of H. pylori . METHODS A total of 268 patients ( mean age , 53.7 + /- 15.8 years ; 142 male and 126 female ; 125 white and 143 nonwhite ) was tested for H. pylori infection by [13C]urea breath test ( UBT ) , measurement of serum immunoglobulin ( Ig ) G and IgA antibody levels , and antral biopsy specimens for CLO test , histology , and Warthin-Starry stain . No patient received specific treatment for H. pylori before testing . The infection status for each patient was established by a concordance of test results . RESULTS Warthin-Starry staining had the best sensitivity and specificity , although CLO test , UBT , and IgG levels were not statistically different in determining the correct diagnosis . The absence of chronic antral inflammation was the best method to exclude infection . Stratification of results by clinical characteristics showed that UBT and chronic inflammation were the best predictors of H. pylori status in patients older than 60 years of age . IgA was a better predictor in white patients . CONCLUSIONS The noninvasive UBT and IgG serology test are as accurate in predicting H. pylori status in untreated patients as the invasive tests of CLO and Warthin-Starry", "We r and omly assigned 45 adult patients with Campylobacter pylori-confirmed antral gastritis to 8 days of treatment with 1 g amoxycillin suspension twice a day , or placebo , according to a double-blind study design . At the end of therapy , 91 % of patients treated with amoxycillin demonstrated clearance of the organism from the antrum , compared with 16 % in the placebo group ( p less than 0.001 ) . Active antral gastritis resolved in 68 % of patients in the amoxycillin group versus only 9 % in the placebo group ( p less than 0.001 ) . No significant difference was observed when looking at the evolution of chronic only gastritis . No significant improvement was observed in the assessment of clinical symptoms and endoscopic appearance . Reappearance of C. pylori and significant worsening of the histological score of active gastritis was observed after 2 wk in all patients . In a second study phase , 18 patients initially not cleared of their bacteria received amoxycillin single blind for 14 days . Clearance of bacteria associated with improvement or resolution of active gastritis was observed in 72 % of the cases . In this subgroup , all patients investigated after 1 month were recolonized with C. pylori and , again , had histological active gastritis . We conclude that amoxycillin is effective in treating active antral gastritis associated with C. pylori , but not in preventing relapses , which occur in all cases within 1 month after therapy", "Efficacy of one-week triple antimicrobial therapy ( bismuth , tinidazole , amoxicillin ) as compared to the same drug combination given for 4 weeks was assessed in children with Helicobacter pylori ( H. pylori ) gastritis and non-ulcer dyspepsia . Twenty-six patients ( group A ) and 30 ( group B ) had one-week and four-week schedule , respectively . Eradication ( absence of organism at endoscopy at least 1 month after ending treatment ) was achieved in 84.6 % of group A ( 22 ) and 83.3 % of group B ( 25 ) , with marked reduction of histological gastritis score in both groups . Among patients with eradicated H. pylori , symptoms improved significantly in 14 and 16 patients of group A and B , respectively , but were still present in 17 ( 8 group A , 9 group B ) . The latter showed gastroparesis and abnormal gastro-oesophageal reflux at a subsequent diagnostic work-up and improved with prokinetic therapy . In 3 patients of group A and 3 of group B , symptoms improved despite persistence of bacterium into the stomach . Finally , in 3 cases ( 1 group A , 2 group B ) both symptoms and H. pylori infection were unchanged . At 6 month follow-up , symptoms were present in 7 patients ( 3 group A , 4 group B ) : 6 of them ( 3 group A , 3 group B ) showed H. pylori gastritis at endoscopy . We conclude that in children with dyspepsia and H. pylori gastritis one-week triple antimicrobial schedule is effective in eradicating bacterium ; however , detection of H. pylori gastritis in dyspeptic children does not invariably indicate a pathogenic role of the organism in these patients", "BACKGROUND It is uncertain whether treatment of Helicobacter pylori infection relieves symptoms in patients with nonulcer , or functional , dyspepsia . METHODS We conducted a double-blind , multicenter trial of patients with H. pylori infection and dyspeptic symptoms ( moderate-to-very-severe pain and discomfort centered in the upper abdomen ) . Patients were excluded if they had a history of peptic ulcer disease or gastroesophageal reflux disease and had abnormal findings on upper endoscopy . Patients were r and omly assigned to seven days of treatment with 20 mg of omeprazole twice daily , 1000 mg of amoxicillin twice daily , and 500 mg of clarithromycin twice daily or with omeprazole alone and then followed up for one year . Treatment success was defined as the absence of dyspeptic symptoms or the presence of minimal symptoms on any of the 7 days preceding the 12-month visit . RESULTS Twenty of the 348 patients were excluded after r and omization because they were not infected with H. pylori , were not treated , or had no data available . For the remaining 328 patients ( 164 in each group ) , treatment was successful for 27.4 percent of those assigned to receive omeprazole and antibiotics and 20.7 percent of those assigned to receive omeprazole alone ( P=0.17 ; absolute difference between groups , 6.7 percent ; 95 percent confidence interval , -2.6 to 16.0 ) . After 12 months , gastritis had healed in 75.0 percent of the patients in the group given omeprazole and antibiotics and in 3.0 percent of the patients in the omeprazole group ( P H. pylori eradication were 79 percent and 2 percent . In the group given omeprazole and antibiotics , the rate of treatment success among patients with persistent H. pylori infection was similar to that among patients in whom the infection was eradicated ( 26 percent vs. 31 percent ) . There were no significant differences between the groups in the quality of life after treatment . CONCLUSIONS In patients with nonulcer dyspepsia , the eradication of H. pylori infection is not likely to relieve symptoms", "BACKGROUND The eradication of Helicobacter pylori infection is beneficial in patients with gastric or duodenal ulcers . The value of eradicating the infection in patients with dyspepsia and no evidence of ulcer disease is not known . METHODS We performed a r and omized , placebo-controlled trial comparing the efficacy of treatment for two weeks with 20 mg of omeprazole orally twice daily , 500 mg of amoxicillin three times daily ( with 500 mg of tetracycline three times daily substituted for amoxicillin in patients allergic to penicillin ) , and 400 mg of metronidazole three times daily ( 160 patients ) with that of omeprazole alone ( 158 patients ) for resolving symptoms of dyspepsia in patients with H. pylori infection but no evidence of ulcer disease on upper gastrointestinal endoscopy . Symptoms were assessed with the Glasgow Dyspepsia Severity Score , with resolution of symptoms defined as a score of 0 or 1 in the preceding six months ( maximal score , 20 ) . One year later the patients were assessed to determine the frequency of the resolution of symptoms . RESULTS One month after the completion of treatment , 132 of 150 patients ( 88 percent ) in the group assigned to received omeprazole and antibiotics had a negative test for H. pylori , as compared with 7 of 152 ( 5 percent ) in the group assigned to receive omeprazole alone . One year later , dyspepsia had resolved in 33 of 154 patients ( 21 percent ) in the group given omeprazole and antibiotics , as compared with 11 of 154 ( 7 percent ) in the group given omeprazole alone ( 95 percent confidence interval for the difference , 7 to 22 percent ; P omeprazole and antibiotics , the symptoms resolved in 26 of the 98 patients ( 27 percent ) who had had symptoms for five years or less , as compared with 7 of the 56 patients ( 12 percent ) who had had symptoms for more than five years ( P=0.03 ) . CONCLUSIONS In patients with H. pylori infection and nonulcer , or functional , dyspepsia , treatment with omeprazole and antibiotics to eradicate the infection is more likely to resolve symptoms than treatment with omeprazole alone", "In a placebo controlled prospect i ve clinical trial of bismuth salicylate in helicobacter pylori associated gastritis , 52 adult patients were r and omly allocated to treatment with bismuth salicylate or placebo . Helicobacter pylori were totally cleared in 77 % patients in bismuth group but none in placebo group ( P less than 0.001 ) . Resolution of gastritis ( P less than 0.001 ) and improvement of symptoms ( P less than 0.01 ) were significantly better in patients where H. pylori infection cleared as compared to patients where the infection persisted", "This double blind r and omised study tested the effectiveness of colloidal bismuth subcitrate ( De-Nol ) in non-ulcer dyspepsia ( NUD ) and if any benefit is associated with clearance of Campylobacter pylori ( C pylori ) from the gastric mucosa . Sixty six patients with dyspepsic symptoms , normal abdominal ultrasound , and upper GI endoscopy , were r and omly allocated to placebo or De-Nol for eight weeks . Antral biopsies were taken for bacteriological and histological examination , and endoscopies and clinical question naires were administered before and after treatment . Fifty two patients ( 25 on De-Nol and 27 on placebo ) completed the trial . De-Nol cleared C pylori from 10 of the 12 C pylori positive patients ( 83.3 % ) , whereas placebo did not clear C pylori from any of the eight C pylori positive patients ( p less than 0.01 ) . In patients receiving De-Nol gastritis improved ( p less than 0.01 ) and symptomatic response was better ( p less than 0.001 ) compared with placebo . In the placebo group seven of the 19 C pylori negative patients became positive : this was associated with significant deterioration of symptoms , a phenomenon not seen in the De-Nol treated group", "We have carried out a double blind placebo controlled trial to assess the effects of treatment with colloidal bismuth subcitrate in Helicobacter pylori associated non-ulcer dyspepsia . Eighty patients with dyspepsia , normal upper gastrointestinal appearances at endoscopy and H pylori associated active chronic gastritis on histology of gastric antral biopsies were included in the trial . The patients were r and omised to receive colloidal bismuth subcitrate 240 mg twice daily for four weeks or matching placebo and were reassessed four weeks after completing treatment . Twenty-six patients ( 67 % ) receiving colloidal bismuth subcitrate had normal histology or improved inflammation compared with five ( 13 % ) receiving placebo ( p less than 0.001 ) , and symptoms were absent or improved in 32 ( 82 % ) and two ( 5 % ) respectively ( p less than 0.001 ) . Serum IgG level was a marker of infection , and fell with successful treatment . Colloidal bismuth subcitrate is effective treatment for H pylori associated non-ulcer dyspepsia with improved gastric antral histological appearances and has a beneficial effect on symptoms", "BACKGROUND The relation between Helicobacter pylori infection and nonulcer dyspepsia is uncertain . We tested the hypothesis that curing the infection will relieve symptoms of dyspepsia . METHODS We r and omly assigned 170 H. pylori-infected patients with nonulcer dyspepsia to receive twice-daily treatment with 20 mg of omeprazole , 1000 mg of amoxicillin , and 500 mg of clarithromycin for 14 days and 167 such patients to receive identical-appearing placebos ; all patients were then followed through regular visits for 12 months . Symptoms were scored on diary cards for seven days before each visit . A carbon-13 urea breath test was performed at base line and repeated at 1 and 12 months , and endoscopic biopsy was performed at 12 months to determine H. pylori status . Treatment was considered successful if the patient had only mild pain or discomfort or none at all . RESULTS The rate of eradication of H. pylori infection was 90 percent in the active-treatment group and 2 percent in the placebo group at four to six weeks ( P rate of successful treatment ( 46 percent in the active-treatment group and 50 percent in the placebo group ; relative likelihood of success with active treatment , 0.93 ; 95 percent confidence interval , 0.73 to 1.18 ; P=0.56 ) . There was also no significant difference in the rate of successful treatment at 12 months between patients who were H. pylori-negative and those who were H. pylori-positive ( 48 percent vs. 49 percent ) . The rates of successful treatment were also similar when patients were analyzed according to the type of dyspepsia ( ulcer-like , reflux-like , or dysmotility-like ) and changes in the quality of life . There was no significant association between treatment success and histologic improvement in chronic gastritis at 12 months ( P=0.68 ) . CONCLUSIONS We found no evidence that curing H. pylori infection in patients with nonulcer dyspepsia leads to relief of symptoms", "Objective This study was intended to investigate the effect of ranitidine in dual anti-Helicobacter pylori therapy . Simultaneously , it was to evaluate the potential effect of H. pylori eradication on the symptomatology of H. pylori-positive dyspepsia . Patients and methods Fifty-four patients with H. pylori infection and symptoms of non-ulcer dyspepsia were r and omly assigned to treatment with either amoxycillin 500 mg four times daily plus ranitidine 300 mg four times daily , clarithromycin 500 mg twice daily plus ranitidine 300 mg twice daily , clarithromycin 500 mg four times daily plus ranitidine 300 mg twice daily or clarithromycin 500 mg four times daily plus ranitidine 300 mg four times daily for a period of 12 days . In addition , ranitidine 150 mg twice daily was given for a further 16 days . Results Eradication of H. pylori using the assigned treatments was achieved in 47 % ( seven out of 15 ) , 50 % ( five out of 10 ) , 70 % ( seven out of 10 ) and 77 % ( 10 out of 13 ) of patients , respectively . Failure of therapy with clarithromycin was associated with primary or acquired resistance after treatment in 91 % ( 10 out of 11 ) . Symptom improvement was significant ( P= 0.0001 ) and similar in all of the four treatment groups up to week 8 . As regards H. pylori status , no differences in the mean symptom score improvement could be found between patients with eradication and those with persistent infection ( 12.3–7.0 , P= 0.0001 , n = 29 compared with 13.0–6.5 , P= 0.004 , n = 19 ) . After 1 year the symptom score had increased both in patients with persistent H. pylori ( 9.1 ) and in those remaining free of infection ( 10.0 ) . No reinfection could be found . Conclusion These results suggest that clarithromycin plus high-dose ranitidine is a combination which achieves reasonably high H. pylori eradication rates . However , treatment failure inevitably leads to clarithromycin resistance . The improvement of non-ulcer dyspepsia symptoms during acute therapy is independent of H. pylori eradication . Long-term benefit of H. pylori eradication with respect to the symptoms of functional dyspepsia was not observed" ]

[ "Purpose To evaluate a new clinical test , the resisted supination external rotation test , for the diagnosis of superior labral anterior posterior lesions of the shoulder . Study Design Cohort study ( diagnosis ) ; Level of evidence , 2 . Methods Forty athletes ( average age , 23.9 years ) with activity-related shoulder pain were enrolled in the study . The patients underwent 3 different tests design ed specifically to detect superior labral anterior posterior lesions ( the resisted supination external rotation test , the crank test , and the active compression test ) ; the tests were performed in a r and om order on the affected shoulder . The results of the tests were compared with arthroscopic findings . Results Out of 40 athletes , 29 ( 72.5 % ) had superior labral anterior posterior tears . The resisted supination external rotation test had the highest sensitivity ( 82.8 % ) , specificity ( 81.8 % ) , positive predictive value ( 92.3 % ) , negative predictive value ( 64.3 % ) , and diagnostic accuracy ( 82.5 % ) of all tests performed . Conclusion By re-creating the peel-back mechanism , the resisted supination external rotation test is more accurate than 2 other commonly used physical examination tests design ed to diagnose superior labral anterior posterior tears in overhead-throwing athletes . By using this test in the context of a thorough clinical history and physical examination , lesions of the superior labrum can be more reliably diagnosed", "BACKGROUND Chronic refractory spinal pain poses a peculiar diagnostic challenge because of multiple putative pain sources , overlapping clinical features , and nonspecific radiologic findings . Diagnostic injection techniques are employed to isolate the source ( s ) of pain . Facet or zygapophysial joint pain is an example of spinal pain diagnosed by local anesthetic injections of the facet joint or its nerve supply . Diagnostic facet joint injections are expected to meet the cardinal features of a diagnostic test ( i.e. , accuracy , safety and reproducibility ) . Accuracy must be compared with a \" gold \" or criterion st and ard that can confirm presence or absence of a disease . There is , however , no available gold st and ard , such as biopsy , to measure presence or absence of pain . Hence , there is a degree of uncertainty concerning the accuracy of diagnostic facet joint injections . OBJECTIVES To evaluate accuracy , safety and reproducibility of facet or zygapophysial joint injections in diagnosing chronic spinal pain of facet joint origin . STUDY DESIGN A systematic review of the literature for clinical studies on efficacy and utility of facet joint/nerve injections in diagnosing spinal pain from facet joints . METHODS Relevant literature on diagnostic facet injections was identified through data base search es . Excluded were abstract s , review s , book chapters , case reports and studies based on single blocks or blocks without radiologic control . Prospect i ve studies with placebo control , or controlled comparative local anesthetic blocks , were given priority over retrospective studies . Each study was grade d using AHRQ and QUADAS criteria . The level of evidence was classified as conclusive , strong , moderate , limited , or inconclusive . RESULTS Available literature pointed to strong evidence for controlled comparative local anesthetic facet joint medial branch blocks in the diagnosis of neck and low back pain . There was moderate evidence in the diagnosis of pain arising from thoracic facet joints . CONCLUSION The evidence obtained from literature review suggests that controlled comparative local anesthetic blocks of facet joint nerves ( medial branch or dorsal ramus ) are reproducible , reasonably accurate , and safe . The sensitivity , specificity , false-positive rates , and predictive values of these diagnostic tests for neck and low back pain have been vali date d and reproduced in multiple studies", "We describe the biceps load test for evaluating the integrity of the superior glenoid labrum in shoulders with recurrent anterior dislocations . With the shoulder in an abducted , externally rotated position and the forearm supinated , active flexion of the elbow against resistance relieves the discomfort of a st and ard apprehension test for anterior shoulder instability . A group of 75 patients with proven unilateral anterior shoulder dislocations were prospect ively examined in a double-blind fashion with arthroscopic examination and the biceps load test . Sixty-three patients had a negative test and 62 of these had an intact biceps tendon-superior labrum complex ; the remaining patient had a type II superior labral anterior and posterior lesion . Twelve patients had positive tests , and 10 had superior labral lesions ; the other 2 patients had intact superior labra . Therefore , the biceps load test revealed a sensitivity of 90.9 % , a specificity of 96.9 % , a positive predictive value of 83 % , a negative predictive value of 98 % , and a kappa coefficient of 0.846", "Background Tears of the superior labrum of the shoulder , anterior to posterior , are difficult to diagnose clinical ly . Purpose We examined whether the crank or O'Brien tests were reliable tools for detecting glenoid labral tears . Study Design Nonr and omized prospect i ve study . Methods Results of diagnostic shoulder arthroscopy were compared with those of the preoperative tests and magnetic resonance imaging for 65 patients who had symptoms of shoulder pain . Results The crank test result was positive in 29 patients ( 45 % ) , and the O'Brien test was positive in 41 patients ( 63 % ) . The crank test had a positive predictive value of 41 % , was 56 % specific , 46 % sensitive , and had a negative predictive value of 61 % . The O'Brien test had a positive predictive value of 34 % , was 31 % specific , 54 % sensitive , and had a negative predictive value of 50 % . Magnetic resonance imaging had a positive predictive value of 63 % , was 92 % specific , 42 % sensitive , and had a negative predictive value of 83 % . Conclusions The O'Brien and crank tests were not sensitive clinical indicators for detecting glenoid labral tears and other tears of the anterior and posterior labrum . Results were often falsely positive for patients with other shoulder conditions , including impingement or rotator cuff tears", "Labral tears and acromioclavicular joint abnormalities were differentiated on physical examination using a new diagnostic test . The st and ing patient forward flexed the arm to 90 ° with the elbow in full extension and then adducted the arm 10 ° to 15 ° medial to the sagittal plane of the body and internally rotated it so that the thumb pointed downward . The examiner , st and ing behind the patient , applied a uniform downward force to the arm . With the arm in the same position , the palm was then fully supinated and the maneuver was repeated . The test was considered positive if pain was elicited during the first maneuver , and was reduced or eliminated with the second . Pain localized to the acromioclavicular joint or “ on top ” was diagnostic of acromioclavicular joint abnormality , whereas pain or painful clicking described as “ inside ” the shoulder was considered indicative of labral abnormality . A prospect i ve study was performed on 318 patients to determine the sensitivity , specificity , and positive and negative predictive values of the test . Fifty-three of 56 patients whose preoperative examinations indicated a labral tear had confirmed labral tears that were repaired at surgery . Fifty-five of 62 patients who had pain in the acromioclavicular joint and whose preoperative examinations indicated abnormalilties in the joint had positive clinical , operative , or radiographic evidence of acromioclavicular injury . There were no false-negative results in either group", "Background Although there are many studies describing tests for shoulder instability , there are few assessing the validity of these tests in diagnosing anterior shoulder instability . Purpose To assess the validity of the apprehension , relocation , and surprise tests as predictors of anterior shoulder instability . Study Design Retrospective review of prospect ively collected data . Methods Forty-six patients with a clear diagnosis of one of the following shoulder disorders were evaluated by four independent , blinded examiners : traumatic anterior instability ( 18 ) , rotator cuff tendinosis ( 17 ) , posterior instability ( 2 ) , glenohumeral osteoarthritis ( 4 ) , or multidirectional instability ( 5 ) . Interobserver reliability was also determined . Results In subjects who had a feeling of apprehension on all three tests , the mean positive and negative predictive values were 93.6 % and 71.9 % , respectively . The surprise test was the single most accurate test ( sensitivity = 63.89 % ; specificity = 98.91 % ) . An improvement in the feeling of apprehension or painwith the relocation test added little to the value of the tests . Interobserver reliability was determined to be 0.83 . Conclusions and Clinical Relevance The results of this study suggest that a positive instability exam on all three tests is highly specific and predictive of traumatic anterior glenohumeral instability", "PURPOSE The purpose of this report is to describe the biceps load test II for evaluating the superior labral anterior and posterior ( SLAP ) lesions . TYPE OF STUDY This is a double-blind study in consecutive data , which includes diagnostic accuracy of a test using sensitivity , specificity , and interexaminer reliability . METHODS In the supine position , the arm is elevated to 120 degrees and externally rotated to its maximal point , with the elbow in the 90 degrees flexion and the forearm in the supinated position . The patient is asked to flex the elbow while resisting the elbow flexion by the examiner . The test is considered positive if the patient complains of pain during the resisted elbow flexion . The test is negative if pain is not elicited or if the pre-existing pain during the elevation and external rotation of the arm is unchanged or diminished by the resisted elbow flexion . A prospect i ve study was performed in 127 patients to evaluate the diagnostic accuracy for the biceps load test II . Two independent examiners were assigned to perform the new diagnostic test . The results of the tests were confirmed during the arthroscopic examination . RESULTS A positive test result in 38 subjects correlated with a SLAP lesion in 35 patients and an intact biceps-superior labrum in 3 patients . A negative test result in 89 patients correlated with an intact superior labrum complex in 85 patients , whereas 4 patients with a negative test result had a type II SLAP lesion . The biceps load test II had a sensitivity of 89.7 % , a specificity of 96.9 % , a positive-predictive value of 92.1 % , a negative-predictive value of 95.5 % , and a kappa coefficient of 0.815 . The abduction and external rotation of the shoulder during the test changes the relative direction of the biceps fiber in a position of oblique angle to the posterosuperior labrum . The resisted contraction of the biceps increases the pain generated on the superior labrum that is already peeled off the glenoid margin in the abducted and externally rotated position . CONCLUSIONS The biceps load test II is an effective diagnostic test for SLAP lesions", "BACKGROUND Although traumatic anterior shoulder instability is common , the usefulness of various physical examination tests as tools for the diagnosis of this condition has been studied infrequently . We hypothesized that ( 1 ) such tests would be specific but not sensitive for this condition , ( 2 ) the usefulness of the anterior drawer test would be limited because of pain during the test , and ( 3 ) an anterior drawer test would be a useful adjunct for making the diagnosis if it reproduced the instability symptoms . METHODS Between 2000 and 2004 , 363 patients underwent a physical examination followed by shoulder arthroscopy . Forty-six patients with traumatic anterior shoulder instability that had been noted arthroscopically or documented radiographically after the trauma were included in our study group , and the remaining patients served as controls . The clinical usefulness of three tests ( anterior apprehension , relocation , and anterior drawer tests ) performed during the physical examination to make a diagnosis of traumatic anterior instability then was evaluated with statistical methods to assess their sensitivity , specificity , and likelihood ratios . RESULTS If demonstration ( or relief ) of apprehension was used as the diagnostic criterion for a positive test , the sensitivity , specificity , and likelihood ratio were 72 % , 96 % , and 20.2 , respectively , for the apprehension test and 81 % , 92 % , and 10.4 , respectively , for the relocation test . If pain ( or relief of pain ) was used as the diagnostic criterion for a positive test , the values for the sensitivity , specificity , and likelihood ratio of both tests were lower . The anterior drawer test could be performed successfully in the physician 's office for 87 % of the patients . If reproduction of instability symptoms was used as the criterion for a positive anterior drawer test , the sensitivity , specificity , and likelihood ratio values of that test were 53 % , 85 % , and 3.6 , respectively . CONCLUSIONS The three physical examination tests for traumatic anterior shoulder instability are specific but not sensitive . Apprehension is a better criterion than pain for a positive apprehension or relocation test . The anterior drawer test ( when pain does not prevent it from being performed ) is helpful for diagnosing traumatic anterior instability . LEVEL OF EVIDENCE Diagnostic Level I. See Instructions to Authors for a complete description of levels of evidence", "We conducted this study to determine whether a test , the posterior impingement maneuver , could be used to prospect ively identify articular side tears of the rotator cuff and /or posterior labrum . Sixty-nine athletes presented with posterior shoulder pain that developed during overh and athletics . Injured shoulders were placed into 90 degrees to 110 degrees of abduction , slight extension , and maximum external rotation , and an effort was made to elicit pain deep within the posterior aspect . Overall sensitivity of the test was 75.5 % , and specificity was 85 % . When only athletes with noncontact injuries ( gradual onset of pain ) were considered , sensitivity was 95 % and specificity was 100 % . A positive posterior impingement sign correlated highly with undersurface tearing of the rotator cuff and /or tearing of the posterior labrum in athletes with gradual onset of posterior shoulder pain during overh and athletics", "PURPOSE Although several clinical tests for detecting superior labral injury of the shoulder have been reported , some of the maneuvers involved are complicated and diagnosis is still inaccurate . The purpose of this report is to introduce our forced shoulder abduction and elbow flexion test ( forced abduction test ) along with an assessment of its efficacy in the throwing shoulder in comparison with other clinical tests . TYPE OF STUDY Prospect i ve nonr and omized clinical trial . METHODS Fifty-four throwing athletes who underwent arthroscopic surgery were prospect ively studied . Superior labral injury was present in 24 cases ( Snyder 's classification was type 2 in 22 , and type 3 in 2 ) . Several clinical tests were performed preoperatively and the results were recorded on our original chart . The condition of the superior labrum was then examined during arthroscopic surgery . The results of these tests were compared with the arthroscopic findings as a st and ard . The forced abduction test was defined as positive when pain at the posterosuperior aspect of the shoulder on forced maximal abduction was relieved or diminished by elbow flexion . RESULTS The sensitivity , specificity , and accuracy of the forced abduction test were 67 % , 67 % , and 67 % , respectively . It was one of the most useful tests , along with the crank test and O'Brien 's test ( crank test , 58 % , 72 % , 66 % ; O'Brien 's test , 54 % , 60 % , 57 % ; respectively ) . Furthermore , the results of the forced abduction test showed a significant correlation with the presence of superior labral injury ( P = .0275 , chi-square test ) . CONCLUSIONS The forced abduction test was technically simple and its usefulness was comparable to the O'Brien 's and crank tests for diagnosing superior labral injury in throwing shoulders . LEVEL OF EVIDENCE Level II", "A positive Speed 's test result is usually thought to suggest inflammation or lesions related to the biceps/labral complex . The specificity , sensitivity , and positive and negative predictive values are determined for the Speed 's test . A prospect i ve study design was developed for all patients with shoulder pain who presented between October 1 , 1994 and February 28 , 1995 . The clinical results of the Speed 's test were correlated with biceps/labral pathology by direct arthroscopic visualization . A neuroprobe is used to pull the biceps tendon into the articular portion of the glenohumeral joint so as to visualize the biceps tendon at the level of the bicipital groove . Forty-six shoulders in 45 patients , 31 men ( average age , 53 years ; range , 16 to 76 years ) and 14 women ( average age , 64 years ; range , 30 to 80 years ) with 26 dominant and 20 nondominant extremities were operated on during this time interval . The clinical evaluation showed that the speed 's test was positive in 40 shoulders . Biceps/labral complex pathology was present in 10 of these patients . A specificity of 13.8 % , a sensitivity of 90 % , a positive predictive value of 23 % , and a negative predictive value of 83 % were calculated . Thus , it is concluded that the Speed 's test is a nonspecific but sensitive test for macroscopic biceps/labral pathology . This clinical examination is positive with a various number of other pathological shoulder problems", "PURPOSE The purpose of this study was to explore and describe reasons for variation in diagnostic accuracy of clinical tests using Yergason 's and Speed 's tests in predicting biceps tendon pathology and SLAP lesions . Shoulder arthroscopy was used as the gold st and ard . TYPE OF STUDY Prospect i ve blinded study of consecutive patients with a wide spectrum of shoulder conditions . METHODS One hundred fifty-two subjects ( 65 women and 87 men ) with complaints of shoulder pain were examined . Fifty subjects ( 16 women and 34 men ) ranging in age from 24 to 79 years ( mean age , 50 years ; SD = 14.36 ) met the criteria for surgery . The validity of the Yergason 's and Speed 's tests was evaluated against findings at surgery . RESULTS The surgical findings related to biceps pathology and SLAP lesions were as follows : 2 bicipital tendonitis , both associated with significant rotator cuff pathology ; 10 biceps partial tears ; and 2 complete ruptures . Fifteen patients had SLAP lesion type I , 12 type II , and 1 type IV . The sensitivity , specificity , and positive and negative predictive values were 43 % , 79 % , 60 % , and 65 % for Yergason 's test and 32 % , 75 % , 50 % , and 58 % for Speed 's test , respectively . The likelihood ratios were 1.28 and 0.91 for Speed 's test and 2.05 and 0.72 for Yergason 's test . These ratios were provided to assist clinicians in calculating the probability of biceps pathology and SLAP lesions for a single patient with a different history-specific prevalence of having the pathology . CONCLUSIONS Although Speed 's and Yergason 's tests are moderately specific , they do not generate a large change in the post-test probability and are unlikely to make a significant change in the pretest diagnosis . Clinicians should underst and that clinical examination tests do not perform consistently and have variable predictive values in different patient population s and setting s. LEVEL OF EVIDENCE Level I diagnostic study : testing of previously developed criteria in a series of consecutive patients ( using surgery as gold st and ard )", "This study documents the sensitivity and specificity of a clinical test to aid in the diagnosis of superior glenoid labral lesions . The anterior slide test , a method of applying an anteriorly and superiorly directed force to the glenohumeral joint , was performed on several groups of athletes . These included symptomatic athletes with isolated superior labral tears , rotator cuff tears , and instabilities , and asymptomatic athletes with rotational deficits . In addition , non-throwing athletes were tested . The sensitivity of the test was 78.4 % , and the specificity was 91.5 % . This study shows that the anterior slide test can be used in the clinical examination , in that it has high specificity for superior labral lesions , but not enough sensitivity to be the sole diagnostic criterion for these lesions", "The purpose of this study was to assess the diagnostic accuracy of transdeltoid palpation ( the rent test ) for the diagnosis of full thickness rotator cuff tear . Clinical and arthroscopic findings were documented prospect ively for 109 consecutive patients undergoing shoulder arthroscopy by the senior author . A retrospective analysis was then performed on these data to assess the accuracy of transdeltoid palpation in the diagnosis of full thickness rotator cuff tear . Transdeltoid palpation was found to have a sensitivity of 95.7 % and specificity of 96.8 % for the diagnosis of full thickness rotator cuff tear . The positive and negative predictive values for transdeltoid palpation were 95.7 % and 96.8 % , respectively . Overall , the diagnostic accuracy of transdeltoid palpation was 96.3 % . We conclude that transdeltoid palpation is highly accurate for the clinical diagnosis of full thickness rotator cuff tear", "BACKGROUND Rotator cuff lesions are common in the community but reproducibility of tests for shoulder assessment has not been adequately appraised and there is no uniform approach to their use . OBJECTIVE To study interrater reproducibility of st and ard tests for shoulder evaluation among a rheumatology specialist , rheumatology trainee , and research nurse . METHODS 136 patients were review ed over 12 months at a major teaching hospital . The three assessors examined each patient in r and om order and were unaware of each other 's evaluation . Each shoulder was examined in a st and ard manner by recognised tests for specific lesions and a diagnostic algorithm was used . Between-observer agreement was determined by calculating Cohen 's kappa coefficients ( measuring agreement beyond that expected by chance ) . RESULTS Fair to substantial agreement was obtained for the observations of tenderness , painful arc , and external rotation . Tests for supraspinatus and subscapularis also showed at least fair agreement between observers . 40/55 ( 73 % ) kappa coefficient assessment s were rated at > 0.2 , indicating at least fair concordance between observers ; 21/55 ( 38 % ) were rated at > 0.4 , indicating at least moderate concordance between observers . CONCLUSION The reproducibility of certain tests , employed by observers of varying experience , in the assessment of the rotator cuff and general shoulder disease was determined . This has implication s for delegation of shoulder assessment to nurse specialists , the development of a simplified evaluation schedule for general practitioners , and uniformity in epidemiological research studies", "BACKGROUND This prospect i ve study was performed to determine which clinical and imaging tests were most helpful for diagnosing acromioclavicular joint pain . METHODS Of 1037 patients with shoulder pain , 113 who mapped pain within an area bounded by the midpart of the clavicle and the deltoid insertion were eligible for inclusion in the study . Forty-two subjects agreed to participate , and four of them were lost to follow-up . Twenty clinical tests , radiography , bone-scanning , magnetic resonance imaging , and an acromioclavicular joint injection test were performed on all patients . The patients were divided into two groups according to whether they had a > or = 50 % decrease in pain following the acromioclavicular joint injection . Statistical analysis , including multivariate regression analysis , was performed in order to evaluate the diagnostic effectiveness of the various tests . RESULTS Acromioclavicular joint pain was confirmed in twenty-eight of the thirty-eight patients . The most sensitive tests were examination for acromioclavicular tenderness ( 96 % sensitivity ) , the Paxinos test ( 79 % ) , magnetic resonance imaging ( 85 % ) , and bone-scanning ( 82 % ) , but these studies had low specificity . In the stepwise regression model , with the response to the injection used as the dependent variable , bone-scanning and the Paxinos test were the only independent variables retained . Patients with a positive Paxinos test as well as a positive bone scan had high post-test odds ( 55:1 ) and a 99 % post-test probability of having pain due to pathological changes in the acromioclavicular joint . The likelihood ratio for patients with one negative test and one positive test was indeterminate ( 0.4:1 ) . Patients with both a negative Paxinos test and a negative bone scan had a likelihood ratio of 0.03:1 for having acromioclavicular joint pain , which basically rules out the disorder . CONCLUSIONS The highly sensitive tests had low specificity , and the highly specific tests had low sensitivity . However , the combination of a positive Paxinos test and a positive bone scan predicted damage to the acromioclavicular joint as the cause of shoulder pain with a high degree of confidence", "STUDY DESIGN Prospect i ve blinded comparison of clinical examination and surgical findings of consecutive patients seen at a tertiary shoulder center . OBJECTIVE To investigate the validity of the supraspinatus test in diagnosing rotator cuff pathology using arthroscopy or open surgery as reference st and ards . A positive supraspinatus test was defined as pain for all types of rotator cuff pathology and weakness for full-thickness tears . BACKGROUND Rotator cuff tenopathy is a very common condition . However , there have been relatively few studies documenting the validity of physical examination for this condition and further investigation of the measurement properties of these tests is warranted . METHODS AND MEASURES One hundred two consecutive subjects were examined . Fifty subjects , ranging in age between 24 and 79 years ( mean age , 50 years ; SD , 14.4 years ) and composed of 16 females and 34 males , underwent surgery . RESULTS The sensitivity of the supraspinatus test was 62 % , 41 % , and 88 % for \" supraspinatus tendonitis or partial thickness tear , \" \" full-thickness tear , \" and \" large to massive tears , \" respectively . The specificity values were 54 % , 70 % , and 70 % for the above conditions , respectively . The negative likelihood ratios varied from 0.17 to 0.84 , and the positive likelihood ratios varied from 1.35 to 2.93 , depending on the presence of pain or weakness . CONCLUSION Application of the supraspinatus test in isolation is helpful in diagnosing large or massive rotator cuff tears . The change that this test makes in pretest probability of less extensive rotator cuff pathology is insignificant", "You are back where we put you in the previous article1 on diagnostic tests in this series on how to use the medical literature : in the library study ing an article that will guide you in interpreting ventilation-perfusion ( V/Q ) lung scans . Using the criteria in Table 1 , you have decided that the Prospect i ve Investigation of Pulmonary Diagnosis ( PIOPED ) study 2 will provide you with valid information . Just then , another", " Thirteen overh and -throwing athletes who failed at least 3 months of physical therapy while restricted from throwing and who demonstrated a positive modified relocation test at 90 degrees , 110 degrees , and /or 120 degrees were clinical ly and arthroscopically examined . On arthroscopic examination , all patients demonstrated articular surface pathology . Eleven patients had fraying of the undersurface of the rotator cuff , and 10 patients had fraying of the posterosuperior labrum . With 90 degrees shoulder abduction , 8 patients had rotator cuff contact with the posterosuperior labrum . When the shoulder was abducted to 110 degrees , all patients demonstrated such contact . At 120 degrees of abduction , 12 patients revealed contact . The presence or absence of pain during the modified relocation test correlated with the presence or absence of cuff contact with the posterosuperior labrum 79 % of the time . Six patients had a positive modified relocation test at all levels of abduction . These patients included 2 with SLAP lesions , 1 with a Bankart lesion , and 1 with a complete tear of the rotator cuff", "We assessed the relative value of lag signs for the evaluation of rotator cuff rupture in a prospect i ve study of 100 consecutive painful shoulders with impingement syndrome , stages 1 to 3 . Lag signs were compared with the Jobe and lift-off signs . Three tests were design ed to assess the main components of the rotator cuff : the external rotation lag sign ( ERLS ) for the supraspinatus and the infraspinatus tendons , the drop sign for the infraspinatus , and the internal rotation lag sign ( IRLS ) for the subscapularis tendon . For assessment of the supraspinatus and infraspinatus the ERLS was less sensitive but more specific than the jobe sign . The drop sign was the least sensitive but was as specific as the ERLS . Partial ruptures of the supraspinatus remained concealed to the ERLS . For assessment of the subscapularis the IRLS was as specific but more sensitive than the lift-off sign . Partial ruptures of the subscapularis tendon could be missed by the lift-off sign but were detected by the IRLS . The magnitude of the lag correlated with the size of the rupture for both the ERLS and the IRLS . Clinical testing for lag signs was efficient , reproducible , and reliable . In patients with little or no restriction of motion it enhanced the accuracy of clinical diagnosis in rotator cuff lesions" ]

[ "Overweight and obesity affects more than 66 % of the adult population and is associated with a variety of chronic diseases . Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies . Guidelines of the National Heart , Lung , and Blood Institute ( NHLBI ) encourage a 10 % reduction in weight , although considerable literature indicates reduction in health risk with 3 % to 5 % reduction in weight . Physical activity ( PA ) is recommended as a component of weight management for prevention of weight gain , for weight loss , and for prevention of weight regain after weight loss . In 2001 , the American College of Sports Medicine ( ACSM ) published a Position St and that recommended a minimum of 150 min wk(-1 ) of moderate-intensity PA for overweight and obese adults to improve health ; however , 200 - 300 min wk(-1 ) was recommended for long-term weight loss . More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss . To this end , we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain , for weight loss , and prevention of weight regain . Evidence supports moderate-intensity PA between 150 and 250 min wk(-1 ) to be effective to prevent weight gain . Moderate-intensity PA between 150 and 250 min wk(-1 ) will provide only modest weight loss . Greater amounts of PA ( > 250 min wk(-1 ) ) have been associated with clinical ly significant weight loss . Moderate-intensity PA between 150 and 250 min wk(-1 ) will improve weight loss in studies that use moderate diet restriction but not severe diet restriction . Cross-sectional and prospect i ve studies indicate that after weight loss , weight maintenance is improved with PA > 250 min wk(-1 ) . However , no evidence from well- design ed r and omized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss . Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk . Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk . There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain", "Background The SenseWear ™ Armb and ( SWA ) ( BodyMedia , Inc. Pittsburgh , PA ) is a physical activity and lifestyle monitor that objective ly and accurately measures free-living energy balance and sleep and includes software for self-monitoring of daily energy expenditure and energy intake . The real-time feedback of the SWA can improve individual self-monitoring and , therefore , enhance weight loss outcomes . Methods We recruited 197 sedentary overweight or obese adults ( age , 46.8 ± 10.8 y ; body mass index ( BMI ) , 33.3 ± 5.2 kg/m2 ; 81 % women , 32 % African-American ) from the greater Columbia , South Carolina area . Participants were r and omized into 1 of 4 groups , a self-directed weight loss program via an evidence -based weight loss manual ( St and ard Care , n = 50 ) , a group-based behavioral weight loss program ( GWL , n = 49 ) , the armb and alone ( SWA-alone , n = 49 ) , or the GWL plus the armb and ( GWL+SWA , n = 49 ) , during the 9-month intervention . The primary outcome was change in body weight and waist circumference . A mixed-model repeated- measures analysis compared change in the intervention groups to the st and ard care group on weight and waist circumference status after adjusting for age , sex , race , education , energy expenditure , and recruitment wave . Results Body weight was available for 62 % of participants at 9 months ( 52 % st and ard care , 70 % intervention ) . There was significant weight loss in all 3 intervention groups ( GWL , 1.86 kg , P = 0.05 ; SWA-alone , 3.55 kg , P = 0.0002 ; GWL+SWA , 6.59 kg , P the GWL+SWA group achieved significant weight loss at month 9 compared to the St and ard Care group ( P = 0.04 ) . Significant waist circumference reductions were achieved in all 4 groups at month 9 ( St and ard Care , 3.49 cm , P = 0.0004 ; GWL , 2.42 cm , P = 0.008 ; SWA-alone , 3.59 cm , P reduced waist circumference compared to the St and ard Care group . Conclusions Continuous self-monitoring from wearable technology with real-time feedback may be particularly useful to enhance lifestyle changes that promote weight loss in sedentary overweight or obese adults . This strategy , combined with a group-based behavioral intervention , may yield optimal weight loss . Trial Registration Clinical Trials.gov :", "CONTEXT Rapid increases in access to the Internet have made it a viable mode for public health intervention . No controlled studies have evaluated this re source for weight loss . OBJECTIVE To determine whether a structured Internet behavioral weight loss program produces greater initial weight loss and changes in waist circumference than a weight loss education Web site . DESIGN R and omized , controlled trial conducted from April to December 1999 . SETTING AND PARTICIPANTS Ninety-one healthy , overweight adult hospital employees aged 18 to 60 years with a body mass index of 25 to 36 kg/m(2 ) . Analyses were performed for the 65 who had complete follow-up data . INTERVENTIONS Participants were r and omly assigned to a 6-month weight loss program of either Internet education ( education ; n = 32 with complete data ) or Internet behavior therapy ( behavior therapy ; n = 33 with complete data ) . All participants were given 1 face-to-face group weight loss session and access to a Web site with organized links to Internet weight loss re sources . Participants in the behavior therapy group received additional behavioral procedures , including a sequence of 24 weekly behavioral lessons via e-mail , weekly online su bmi ssion of self-monitoring diaries with individualized therapist feedback via e-mail , and an online bulletin board . MAIN OUTCOME MEASURES Body weight and waist circumference , measured at 0 , 3 , and 6 months , compared the 2 intervention groups . RESULTS Repeated- measures analyses showed that the behavior therapy group lost more weight than the education group ( P = .005 ) . The behavior therapy group lost a mean ( SD ) of 4.0 ( 2.8 ) kg by 3 months and 4.1 ( 4.5 ) kg by 6 months . Weight loss in the education group was 1.7 ( 2.7 ) kg at 3 months and 1.6 ( 3.3 ) kg by 6 months . More participants in the behavior therapy than education group achieved the 5 % weight loss goal ( 45 % vs 22 % ; P = .05 ) by 6 months . Changes in waist circumference were also greater in the behavior therapy group than in the education group at both 3 months ( P = .001 ) and 6 months ( P = .005 ) . CONCLUSIONS Participants who were given a structured behavioral treatment program with weekly contact and individualized feedback had better weight loss compared with those given links to educational Web sites . Thus , the Internet and e-mail appear to be viable methods for delivery of structured behavioral weight loss programs", "Background The Internet has potential as a medium for health behavior change programs , but no controlled studies have yet evaluated the impact of a fully automated physical activity intervention over several months with real-time objective feedback from a monitor . Objective The aim was to evaluate the impact of a physical activity program based on the Internet and mobile phone technology provided to individuals for 9 weeks . Methods A single-center , r and omized , stratified controlled trial was conducted from September to December 2005 in Bedfordshire , United Kingdom , with 77 healthy adults whose mean age was 40.4 years ( SD = 7.6 ) and mean body mass index was 26.3 ( SD = 3.4 ) . Participants were r and omized to a test group that had access to an Internet and mobile phone – based physical activity program ( n = 47 ) or to a control group ( n = 30 ) that received no support . The test group received tailored solutions for perceived barriers , a schedule to plan weekly exercise sessions with mobile phone and email reminders , a message board to share their experiences with others , and feedback on their level of physical activity . Both groups were issued a wrist-worn accelerometer to monitor their level of physical activity ; only the test group received real-time feedback via the Internet . The main outcome measures were accelerometer data and self-report of physical activity . Results At the end of the study period , the test group reported a significantly greater increase over baseline than did the control group for perceived control ( P higher level of moderate physical activity in the test group . The average increase ( over the control group ) in accelerometer-measured moderate physical activity was 2 h 18 min per week . The test group also lost more percent body fat than the control group ( test group : −2.18 , SD = 0.59 ; control group : −0.17 , SD = 0.81 ; P = .04 ) . Conclusions A fully automated Internet and mobile phone – based motivation and action support system can significantly increase and maintain the level of physical activity in healthy adults", "Background Obesity remains a major public health challenge , dem and ing cost-effective and scalable weight management programs . Delivering key treatment components via mobile technology offers a potential way to reduce expensive in-person contact , thereby lowering the cost and burden of intensive weight loss programs . The ENGAGED study is a theory-guided , r and omized controlled trial design ed to examine the feasibility and efficacy of an abbreviated smartphone-supported weight loss program . Methods / design Ninety-six obese adults ( BMI 30–39.9 kg/m2 ) will be r and omized to one of three treatment conditions : ( 1 ) st and ard behavioral weight loss ( STND ) , ( 2 ) technology-supported behavioral weight loss ( TECH ) ; or ( 3 ) self-guided behavioral weight loss ( SELF ) . All groups will aim to achieve a 7 % weight loss goal by reducing calorie and fat intake and progressively increasing moderate intensity physical activity to 175 minutes/week . STND and TECH will attend 8 group sessions and receive regular coaching calls during the first 6 months of the intervention ; SELF will receive the Group Lifestyle Balance Program DVD ’s and will not receive coaching calls . During months 1–6 , TECH will use a specially design ed smartphone application to monitor dietary intake , body weight , and objective ly measured physical activity ( obtained from a Blue-tooth enabled accelerometer ) . STND and SELF will self-monitor on paper diaries . Linear mixed modeling will be used to examine group differences on weight loss at months 3 , 6 , and 12 . Self-monitoring adherence and diet and activity goal attainment will be tested as mediators . Discussion ENGAGED is an innovative weight loss intervention that integrates theory with emerging mobile technologies . We hypothesize that TECH , as compared to STND and SELF , will result in greater weight loss by virtue of improved behavioral adherence and goal achievement . Trial registration", "BACKGROUND Several studies have shown that e-mail counseling improves weight loss achieved in self-directed Internet programs . Computer-tailored feedback offers a population -based alternative to human e-mail counseling . METHODS One hundred ninety-two adults , aged 49.2 + /- 9.8 years , having a body mass index ( calculated as weight in kilograms divided by height in meters squared ) of 32.7 + /- 3.5 , were r and omized to 1 of 3 Internet treatment groups : No counseling , computer-automated feedback , or human e-mail counseling . All participants received 1 weight loss group session , coupons for meal replacements , and access to an interactive Web site . The human e-mail counseling and computer-automated feedback groups also had access to an electronic diary and message board . The human e-mail counseling group received weekly e-mail feedback from a counselor , and the computer-automated feedback group received automated , tailored messages . RESULTS Retention was 82 % at 3 months and 80 % at 6 months for all 3 groups . At 3 months , completers in both the computer-automated feedback ( -5.3 + /- 4.2 kg ) and human e-mail counseling ( -6.1 + /- 3.9 kg ) groups had significantly greater weight losses compared with the no counseling group ( -2.8 + /- 3.5 kg ) and these groups did not differ from each other . At 6 months , weight losses were significantly greater in the human e-mail counseling group ( -7.3 + /- 6.2 kg ) than in the computer-automated feedback ( -4.9 + /- 5.9 kg ) or no counseling ( -2.6 + /- 5.7 kg ) groups . Intent-to-treat analyses using single or multiple imputation techniques showed the same pattern of significance . CONCLUSIONS Providing automated computer-tailored feedback in an Internet weight loss program was as effective as human e-mail counseling at 3 months . Further research is needed to improve the efficacy of automated computer-tailored feedback as a population -based weight loss approach", "Background The construct of total wellness includes a holistic approach to the body , mind and spirit components of life . While the health benefits of reducing sedentary behavior and increasing physical activity are well documented , little is known about the influence on total wellness of an internet-based physical activity monitor design ed to help people to achieve higher physical activity levels . Purpose The purpose of this four-week , personal activity monitor-based intervention program was to reduce sedentary behavior and increase physical activity levels in daily living for sedentary adults and to determine if these changes would also be associated with improvement in total wellness . Methods Twenty-two men and 11 women ( 27 years ± 4.0 ) were r and omly assigned to either an intervention ( n = 18 ) or control group ( n = 15 ) . The intervention group interacted with an online personal activity monitor ( Gruve Solution ™ ) design ed to reduce sedentary time and increase physical activity during activities of daily living . The control group did not interact with the monitor , as they were asked to follow their normal daily physical activities and sedentary behavior routines . The Wellness Evaluation of Lifestyle ( WEL ) inventory was used to assess total wellness . Sedentary time , light , walking , moderate and vigorous intensity physical activities were assessed for both intervention and control groups at baseline and at week-4 by the 7-day Sedentary and Light Intensity Physical Activity Log ( 7-day SLIPA Log ) and the International Physical Activity Question naire ( IPAQ ) . Results Significant increases in pre-post total wellness scores ( from 64 % ± 5.7 to 75 % ± 8.5 ) ( t ( 17 ) = -6.5 , p their sedentary time ( 21 % , 2.3 hours/day ) and increased their light ( 36.7 % , 2.5 hours/day ) , walking ( 65 % , 1057 MET-min/week ) , moderate ( 67 % , 455 MET-min/week ) and vigorous intensity ( 60 % , 442 MET-min/week ) physical activity ( all p for total wellness were observed between the groups at baseline and no pre-post significant differences were observed for any outcome variable in the control group . Conclusion Total wellness is improved when sedentary , but sufficiently physically active adults , reduce sedentary time and increase physical activity levels ( i.e. light , waking , moderate and vigorous )", "Background Inactive people are often not aware of the fact that they are insufficiently active . Providing insight into their actual physical activity ( PA ) levels may raise awareness and could , in combination with tailored PA advice , stimulate a physically active lifestyle . Objective This study evaluated the feasibility and effectiveness of a 3-month intervention in which Dutch office workers were provided with a personal activity monitor ( PAM ) coupled to simple and concise Web-based tailored PA advice ( PAM COACH ) . Method Participants were r and omly assigned to the 3-month PAM intervention ( n = 51 ) or received a single written information brochure with brief general PA recommendations ( n = 51 ) . Study outcome measures were changes in PA ( recall of minutes per week spent on PA , as measured by the Activity Question naire for Adolescents and Adults ) , determinants of PA , aerobic fitness , and body composition . Follow-up measurements were performed immediately after the 3-month intervention and at 8-months , 5 months after the end of the 3-month intervention period . Results A total of 102 workers , 23 to 39 years old , completed the baseline measurement at the worksite . 48 completed the 3-month follow up and 38 the 8-month follow-up in the intervention group , 50 completed the 3-month follow up and 42 the 8-month follow up in the control group . 35 out of 48 ( 73 % ) participants in the PAM intervention group reported wearing the PAM regularly , and the PAM COACH was used almost once a week ; 24 out of 46 ( 52 % ) PAM users set a personal goal , and 33 ( 72 % ) entered their favorite activities on the website . Main reasons for not using these items were lack of interest or not being able to find the item on the website . The majority of PAM users ( 34 out of 46 , 74 % ) read the advice , of whom 14 ( 39 % ) found it unappealing . After the 3-month intervention , no significant intervention effect was observed ( adjusted difference in min/week ) for sedentary behavior ( β = 10 , 95 % CI = −435 to 455 ) , light-intensity PA ( β = −129 , 95 % CI = −337 to 79 ) , moderate-intensity PA ( β = −13 , 95 % CI = −89 to 63 ) , vigorous-intensity PA ( β= −6 , 95 % CI = −75 to 62 ) , and moderate- to vigorous-intensity PA ( β = −23 , 95 % CI = −121 to 76 ) . No significant intervention effect was observed in the PA outcomes at the 8-month follow-up . For the determinants of PA , aerobic fitness , and body composition , no statistically significant intervention effect was observed in the total study population immediately after the 3-month intervention or the 8-month follow-up . Conclusions The intervention appeared to be easily applicable to real-life setting s. The intervention was ineffective in improving PA behavior or its determinants in healthy office workers . More attention should have been given to the quality and appropriateness of the tailored advice . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 93896459 ; http://www.controlled-trials.com/IS RCT N93896459/ ( Archived by WebCite at http://www.webcitation.org/5iR3mf7ex", "Background Lack of physical activity ( PA ) is a known risk factor for many health conditions . The workplace is a setting often used to promote activity and health . We investigated the effectiveness of an intervention on PA and productivity-related outcomes in an occupational setting . Methods We conducted a r and omized controlled trial of 12 months duration with two 1:1 allocated parallel groups of insurance company employees . Eligibility criteria included permanent employment and absence of any condition that risked the participant ’s health during PA . Subjects in the intervention group monitored their daily PA with an accelerometer , set goals , had access to an online service to help them track their activity levels , and received counseling via telephone or web messages for 12 months . The control group received the results of a fitness test and an information leaflet on PA at the beginning of the study . The intervention ’s aim was to increase PA , improve work productivity , and decrease sickness absence . Primary outcomes were PA ( measured as MET minutes per week ) , work productivity ( quantity and quality of work ; QQ index ) , and sickness absence ( SA ) days at 12 months . Participants were assigned to groups using block r and omization with a computer-generated scheme . The study was not blinded . Results There were 544 r and omized participants , of which 521 were included in the analysis ( 64 % female , mean age 43 years ) . At 12 months , there was no significant difference in physical activity levels between the intervention group ( n = 264 ) and the control group ( n = 257 ) . The adjusted mean difference was −206 MET min/week [ 95 % Bayesian credible interval −540 to 128 ; negative values favor control group ] . There was also no significant difference in the QQ index ( −0.5 [ −4.4 to 3.3 ] ) or SA days ( 0.0 [ −1.2 to 0.9 ] ) . Of secondary outcomes , body weight ( 0.5 kg [ 0.0 to 1.0 ] ) and percentage of body fat ( 0.6 % [ 0.2 % to 1.1 % ] ) were slightly higher in the intervention group . An exploratory subgroup analysis revealed no subgroups in which the intervention affected physical activity . No adverse events were reported . Conclusions The intervention was not found effective , and this study does not provide support for the effectiveness of the workplace PA intervention used here . Trial registration Clinical Trials.gov identifier :", "Older people are more sedentary than other age groups . We sought to determine if providing an accelerometer with feedback about activity and counseling older subjects using Go4Life educational material would increase activity levels . Participants were recruited from independent living areas within assisted living facilities and the general public in the Rochester , MN area . 49 persons aged 65 - 95 ( 79.5±7.0 years ) who were ambulatory but sedentary and overweight participated in this r and omized controlled crossover trial for one year . After a baseline period of 2 weeks , group 1 received an accelerometer and counseling using Go4Life educational material ( www.Go4Life.nia.nih.gov ) for 24 weeks and accelerometer alone for the next 24 weeks . Group 2 had no intervention for the first 24 weeks and then received an accelerometer and Go4Life based counseling for 24 weeks . There were no significant baseline differences between the two groups . The intervention was not associated with a significant change in activity , body weight , % body fat , or blood parameters ( p>0.05 ) . Older ( 80 - 93 ) subjects were less active than younger ( 65 - 79 ) subjects ( p=0.003 ) . Over the course of the 48 week study , an increase in activity level was associated with a decline in % body fat ( p=0.008 ) . Increasing activity levels benefits older patients . However , providing an accelerometer and a Go4Life based exercise counseling program did not result in a 15 % improvement in activity levels in this elderly population . Alternate approaches to exercise counseling may be needed in elderly people of this age range", "OBJECTIVE The purpose of this study was to develop and evaluate a 12-week weight management intervention involving computerized self-monitoring and technology-assisted feedback with and without an enhanced behavioral component . METHODS 120 overweight ( 30.5±2.6kg/m(2 ) ) adults ( 45.0±10.3 years ) were r and omized to one of three groups : computerized self-monitoring with Basic feedback ( n=45 ) , Enhanced behavioral feedback ( n=45 ) , or wait-list control ( n=30 ) . Intervention participants used a computer software program to record dietary and physical activity information . Weekly e-mail feedback was based on computer-generated reports , and participants attended monthly measurement visits . RESULTS The Basic and Enhanced groups experienced significant weight reduction ( -2.7±3.3 kg and -2.5±3.1 kg ) in comparison to the Control group ( 0.3±2.2 ; p ) . Waist circumference and systolic blood pressure also decreased in intervention groups compared to Control ( p produced significant weight loss after 12 weeks . However , the addition of an enhanced behavioral component did not improve the effectiveness of the program . PRACTICE IMPLICATION S This study suggests that healthcare professionals can effectively deliver a weight management intervention using technology-assisted strategies in a format that may complement and reduce face-to-face sessions", "The purpose of this study was to compare a technology-based system , an in-person behavioral weight loss intervention , and a combination of both over a 6-month period in overweight adults . Fifty-one subjects ( age : 44.2 ± 8.7 years , BMI : 33.7 ± 3.6 kg/m(2 ) ) participated in a 6-month behavioral weight loss program and were r and omized to one of three groups : st and ard behavioral weight loss ( SBWL ) , SBWL plus technology-based system ( SBWL+TECH ) , or technology-based system only ( TECH ) . All groups reduced caloric intake and progressively increased moderate intensity physical activity . SBWL and SBWL+TECH attended weekly meetings . SBWL+TECH also received a TECH that included an energy monitoring armb and and website to monitor energy intake and expenditure . TECH used the technology system and received monthly telephone calls . Body weight and physical activity were assessed at 0 and 6 months . Retention at 6 months was significantly different ( P = 0.005 ) between groups ( SBWL : 53 % , SBWL+TECH : 100 % , and TECH : 77 % ) . Intent-to-treat ( ITT ) analysis revealed significant weight losses at 6 months in SBWL+TECH ( -8.8 ± 5.0 kg , -8.7 ± 4.7 % ) , SBWL ( -3.7 ± 5.7 kg , -4.1 ± 6.3 % ) , and TECH ( -5.8 ± 6.6 kg , -6.3 ± 7.1 % ) ( P increased significantly in SBWL ( 473.9 ± 800.7 kcal/week ) , SBWL+TECH ( 713.9 ± 1,278.8 kcal/week ) , and TECH ( 1,066.2 ± 1,371 kcal/week ) ( P not greater weight losses and changes in physical activity than the st and ard in-person behavioral program at 6 months . The use of this technology may provide an effective short-term clinical alternative to st and ard in-person behavioral weight loss interventions , with the longer term effects warranting investigation", "OBJECTIVE The objective was to examine the efficacy of adding a technology-based program to an in-person , behavioral weight loss intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven subjects ( BMI = 33.1+/-2.8 kg/m2 ; age=41.3+/-8.7 years ) participated in a 12-week intervention with r and om assignment to St and ard In-Person Behavioral Weight Control Program ( SBWP ) or Intermittent or Continuous Technology-Based Program ( INT-TECH , CON-TECH ) . SBWP subjects received seven individualized weight loss sessions encouraging dietary and exercise modifications . INT-TECH and CON-TECH subjects received all SBWP components ; additionally , these groups used a SenseWear Pro Armb and ( BodyMedia , Inc. ) to monitor energy expenditure and an Internet-based program to monitor eating behaviors . These features were used by INT-TECH subjects during weeks 1 , 5 , and 9 and CON-TECH subjects weekly throughout the intervention . RESULTS Intent-to-treat analysis revealed weight loss of 4.1+/-2.8 kg , 3.4+/-3.4 kg , and 6.2+/-4.0 kg , for SBWP , INT-TECH , and CON-TECH groups , respectively ( CON-TECH > INT-TECH , p weight loss . Future studies should examine the long-term and independent effect of this technology on weight loss , and for whom this intervention format is most effective", "OBJECTIVES In order to quantify the effects of physical activity such as walking on chronic disease , accurate measurement of physical activity is needed . The objective of this study was to determine the validity and reliability of a new activity monitor , the Fitbit One , in a population of healthy adults . DESIGN Cross-sectional study . METHODS Thirty healthy adults ambulated at 5 different speeds ( 0.90 , 1.12 , 1.33 , 1.54 , 1.78 m/s ) on a treadmill while wearing three Fitbit One activity monitors ( two on the hips and one in the pocket ) . The order of each speed condition was r and omized . Fitbit One step count output was compared to observer counts and distance output was compared to the calibrated treadmill output . Two-way repeated measures ANOVA , concordance correlation coefficients , and Bl and and Altman plots were used to assess validity and intra-class correlation coefficients ( ICC ) were used to assess reliability . RESULTS No significant differences were noted between Fitbit One step count outputs and observer counts , and concordance was substantial ( 0.97 - 1.00 ) . Inter-device reliability of the step count was high for all walking speeds ( ICC ≥ 0.95 ) . Percent relative error was less than 1.3 % . The distance output of the Fitbit One activity monitors was significantly different from the criterion values for each monitor at all speeds ( P 0.0 - 0.05 ) . Inter-device reliability was excellent for all treadmill speeds ( ICC ≥ 0.90 ) . Percent relative error was high ( up to 39.6 % ) . CONCLUSIONS The Fitbit One activity monitors are valid and reliable devices for measuring step counts in healthy young adults . The distance output of the monitors is inaccurate and should be noted with caution", "Background Previous interventions have shown promising results using theory-based podcasts to deliver a behavioral weight-loss intervention . Objective The objective of our study was to examine whether a combination of podcasting , mobile support communication , and mobile diet monitoring can assist people in weight loss . Methods In this 6-month , minimal contact intervention , overweight ( n = 96 , body mass index 32.6 kg/m2 ) adults were recruited through television advertisements and email listservs and r and omly assigned to Podcast-only or Podcast+Mobile groups . Both groups received 2 podcasts per week for 3 months and 2 minipodcasts per week for months 3–6 . In addition to the podcasts , the Podcast+Mobile group was also instructed to use a diet and physical activity monitoring application ( app ) on their mobile device and to interact with study counselors and other participants on Twitter . Results Weight loss did not differ by group at 6 months : mean –2.7 % ( SD 5.6 % ) Podcast+Mobile , n = 47 ; mean –2.7 % ( SD 5.1 % ) Podcast , n = 49 ; P = .98 . Days/week of reported diet monitoring did not differ between Podcast+Mobile ( mean 2.3 , SD 1.9 days/week ) and Podcast groups ( mean 1.9 , SD 1.7 days/week ; P = .28 ) but method of monitoring did differ . Podcast+Mobile participants were 3.5 times more likely than the Podcast group to use an app to monitor diet ( P = .01 ) , whereas the majority of Podcast participants reported using the Web ( 14/41 , 34 % ) or paper ( 12/41 , 29 % ) . There were more downloads per episode in the Podcast+Mobile group ( 1.4/person ) than in the Podcast group ( 1.1/person ; P number of podcasts participants reported downloading over the 6-month period was significantly moderately correlated with weight loss in both the Podcast+Mobile ( r = –.46 , P = .001 ) and the Podcast ( r = –.53 , P Podcast+Mobile participants felt more user control at 3 months ( P = .02 ) , but not at 6 months , and there was a trend ( P = .06 ) toward greater elaboration among Podcast+Mobile participants . There were significant differences in reported source of social support between groups . More Podcast participants relied on friends ( 11/40 , 28 % vs 4/40 , 10 % ; P = .045 ) whereas Podcast+Mobile participants relied on online sources ( 10/40 , 25 % vs 0/40 ; P = .001 ) . Conclusions Results confirm and extend previous findings showing a minimally intensive weight-loss intervention can be delivered via podcast , but prompting and mobile communication via Twitter and monitoring app without feedback did not enhance weight loss . Trial Registration Clinical trials.gov NCT01139255 ; http:// clinical trials.gov/ct2/show/NCT01139255 ( Archived by WebCite at http://www.webcitation.org/625OjhiDy" ]

[ "OBJECTIVES To study the effect of a combination of thalassotherapy , exercise and patient education in people with fibromyalgia . METHODS Patients with fibromyalgia , selected from a rheumatology out-patient department and from members of the Dutch fibromyalgia patient association , were pre-r and omized to receive either 2(1/2 ) weeks of treatment in a Tunisian spa resort , including thalassotherapy , supervised exercise and group education ( active treatment ) or treatment as usual ( control treatment ) . Primary outcome measure was health-related quality of life , measured with the R AND -36 question naire . Secondary measures included the Fibromyalgia Impact Question naire , the McGill Pain Question naire , the Beck Depression Inventory , tender point score and a 6-min treadmill walk test . RESULTS Fifty-eight participants receiving the active treatment reported significant improvement on R AND -36 physical and mental component summary scales . For physical health , differences from the 76 controls were statistically significant after 3 months , but not after 6 and 12 months . A similar pattern of temporary improvement was seen in the self-reported secondary measures . Tender point scores and treadmill walk tests improved more after active treatment , but did not reach significant between-group differences , except for walk tests after 12 months . CONCLUSIONS A combination of thalassotherapy , exercise and patient education may temporarily improve fibromyalgia symptoms and health-related quality of life", "The aim of this study was to investigate the effect of connective tissue massage in the treatment of individuals with fibromyalgia . The results of this r and om study of 48 individuals diagnosed with fibromyalgia ( 23 in the treatment group and 25 in the reference group ) show that a series of 15 treatments with connective tissue massage conveys a pain relieving effect of 37 % , reduces depression and the use of analgesics , and positively effects quality of life . The treatment effects appeared gradually during the 10-week treatment period . Three months after the treatment period about 30 % of the pain relieving effect was gone , and 6 months after the treatment period pain was back to about 90 % of the basic value . As long as there is a lack of effective medical treatment for individuals with fibromyalgia , they ought to be offered treatments with connective tissue massage . However , further studies are needed in the mechanisms behind the treatment effects . Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain", "OBJECTIVE To determine the prevalence and characteristics of fibromyalgia in the general population . METHODS A r and om sample of 3,006 persons in Wichita , KS , were characterized according to the presence of no pain , non-widespread pain , and widespread pain . A sub sample of 391 persons , including 193 with widespread pain , were examined and interviewed in detail . RESULTS The prevalence of fibromyalgia was 2.0 % ( 95 % confidence interval [ 95 % CI ] 1.4 , 2.7 ) for both sexes , 3.4 % ( 95 % CI 2.3 , 4.6 ) for women , and 0.5 % ( 95 % CI 0.0 , 1.0 ) for men . The prevalence of the syndrome increased with age , with highest values attained between 60 and 79 years ( > 7.0 % in women ) . Demographic , psychological , dolorimetry , and symptom factors were associated with fibromyalgia . CONCLUSION Fibromyalgia is common in the population , and occurs often in older persons . Characteristic features of fibromyalgia -- pain threshold and symptoms -- are similar in community and clinic population s , but overall severity , pain , and functional disability are more severe in the clinic population", "OBJECTIVE To compare 2 exercise modalities , aerobic fitness training and stretching exercises , in patients with fibromyalgia ( FM ) in relation to function , pain , quality of life , depression , and anxiety , and to correlate the cardiorespiratory fitness gain with symptom improvement . METHODS Seventy-six women with FM between 18 and 60 years old were r and omized to either an aerobic program or stretching program , for 20 weeks . They were evaluated at the beginning of the program and after 10 and 20 weeks in relation to the improvement of aerobic fitness , flexibility , function , Fibromyalgia Impact Question naire ( FIQ ) , Short-form Health Survey ( SF-36 ) , and depression and anxiety levels . Ventilatory anaerobic threshold ( VT ) and maximum oxygen uptake ( VO2max ) were determined by expired gas analyses . RESULTS Aerobic exercise was superior to stretching in relation to VO2 max , VT , function , depression , pain , and the emotional aspects and mental health domains of SF-36 . Patients in the stretching group showed no improvement in depression , \" role emotional , \" and \" mental health . \" No association was noted between improvement in aerobic fitness as measured by VT and the improvement of pain , function , or scores in FIQ and SF-36 . CONCLUSION Our results confirm that aerobic exercise is beneficial to patients with FM , but the cardiorespiratory fitness gain is not related to improvement of FM symptoms", "Objective : To evaluate the efficacy of a treatment programme for patients with fibromyalgia ( FM ) based on self management , using pool exercises and education . Methods : R and omised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme ; 164 patients with FM were allocated to an immediate 6 week programme ( n = 84 ) or to a waiting list control group ( n = 80 ) . The main outcomes were changes in quality of life , functional consequences , patient satisfaction and pain , using a combination of patient question naires and clinical examinations . The question naires included the Fibromyalgia Impact Question naire ( FIQ ) , Psychological General Well-Being ( PGWB ) index , regional pain score diagrams , and patient satisfaction measures . Results : 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations . Six months after programme completion , significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ ( total score p = 0.025 ; fatigue p = 0.003 ; depression p = 0.031 ) and PGWB ( total score p = 0.032 ; anxiety p = 0.011 ; vitality p = 0.013 , ) . All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups ; between-group differences were statistically significant for “ control of symptoms ” , “ psychosocial factors ” , and “ physical therapy ” No change in pain was seen . Conclusion : A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment . These improvements are sustained for at least 6 months after programme completion", "Abstract Objectives : To evaluate cardiovascular fitness exercise in people with fibromyalgia Design : R and omised controlled trial Setting : Hospital rheumatology out patients . Group based classes took place at a “ healthy living centre . ” Participants : 132 patients with fibromyalgia . Interventions : Prescribed grade d aerobic exercise ( active treatment ) and relaxation and flexibility ( control treatment ) . Main outcome measures : Participants ' self assessment of improvement , tender point count , impact of condition measured by fibromyalgia impact question naire , and short form McGill pain question naire . Results : Compared with relaxation exercise led to significantly more participants rating themselves as much or very much better at three months : 24/69 ( 35 % ) v 12/67 ( 18 % ) , P=0.03 . Benefits were maintained or improved at one year follow up when fewer participants in the exercise group fulfilled the criteria for fibromyalgia ( 31/69 v 44/67 , P=0.01 ) . Peoplein the exercise group also had greater reductions in tender point counts ( 4.2 v 2.0 , P=0.02 ) and in scores on the fibromyalgia impact question naire ( 4.0 v 0.6 , P=0.07 ) . Conclusions : Prescribed grade d aerobic exercise is a simple , cheap , effective , and potentially widely available treatment for fibromyalgia", "OBJECTIVE To evaluate the effects of 6 months of pool exercise combined with a 6 session education program for patients with fibromyalgia syndrome ( FM ) . METHODS The study population comprised 58 patients , r and omized to a treatment or a control group . Patients were instructed to match the pool exercises to their threshold of pain and fatigue . The education focused on strategies for coping with symptoms and encouragement of physical activity . The primary outcome measurements were the total score of the Fibromyalgia Impact Question naire ( FIQ ) and the 6 min walk test , recorded at study start and after 6 mo . Several other tests and instruments assessing functional limitations , severity of symptoms , disabilities , and quality of life were also applied . RESULTS Significant differences between the treatment group and the control group were found for the FIQ total score ( p = 0.017 ) and the 6 min walk test ( p physical function , grip strength , pain severity , social functioning , psychological distress , and quality of life . CONCLUSION The results suggest that a 6 month program of exercises in a temperate pool combined with education will improve the consequences of FM", "Abstract . The aim of this study was to evaluate the effectiveness of balneotherapy on patients with fibromyalgia ( FM ) at the Dead Sea . Forty-eight patients with FM were r and omly assigned to a treatment group receiving sulfur baths and a control group . All participants stayed for 10 days at a Dead Sea spa . Physical functioning , FM-related symptoms , and tenderness measurements ( point count and dolorimetry ) were assessed at four time points : prior to arrival at the Dead Sea , after 10 days of treatment , and 1 and 3 months after leaving the spa . Physical functioning and tenderness moderately improved in both groups . With the exception of tenderness threshold , the improvement was especially notable in the treatment group and it persisted even after 3 months . Relief in the severity of FM-related symptoms ( pain , fatigue , stiffness , and anxiety ) and reduced frequency of symptoms ( headache , sleep problems , and subjective joint swelling ) were reported in both groups but lasted longer in the treatment group . In conclusion , treatment of FM at the Dead Sea is effective and safe and may become an additional therapeutic modality in FM . Future studies should address the outcome and possible mechanisms of this treatment in FM patients", "OBJECTIVE To evaluate the efficacy of a 6-week exercise and educational program for patients with fibromyalgia . METHODS Forty-one subjects were r and omly assigned to the program or served as waiting list controls . Program outcome was assessed with a 6-minute walk test , the Fibromyalgia Impact Question naire , a Self-Efficacy Scale , and a \" knowledge \" question naire ( based on information provided during the educational sessions ) . Waiting list control subjects subsequently completed the program . Program outcome was reassessed 3 or 6 months post-program . RESULTS The program produced significant improvements in 6-minute walk distance , well-being , fatigue , self-efficacy ( for controlling pain and other symptoms ) , and knowledge . At followup , immediate gains in walk distance , well-being , and self-efficacy were maintained , but gains in fatigue and knowledge were lost . CONCLUSION Short-term exercise and educational programs can produce immediate and sustained benefits for patients with fibromyalgia . The benefits of our program may be due to exercise or education since both interventions were given", "OBJECTIVE To examine the effectiveness of a supervised aerobic exercise program , a self-management education program , and the combination of exercise and education for women with fibromyalgia ( FM ) . METHODS One hundred fifty-two women were r and omized into one of 4 groups : exercise-only , education-only , exercise and education , or control . The duration of the study was 12 weeks . All subjects were analyzed at 3 times : before study , immediately upon completion , and 3 months after completion of the intervention program on measures of disability , self-efficacy , fitness , tender point count , and tender point tenderness . Of the 152 women , complete data were available for 95 and 69 who complied with the protocol . In order to determine the group time interaction , a 2 way analysis of variance with repeated measures was used for each measure . RESULTS The only significant group time interaction was reported with the compliance analysis for the Self-Efficacy Coping with Other Symptoms subscale and the Six Minute Walk . If the program was followed , the combination of a supervised exercise program and group education provided persons with FM with a better sense of control over their symptoms . Fitness improved in the 2 groups undergoing supervised aerobic exercise programs . However , the improvement in fitness was maintained at followup in the exercise-only group and not the combined group . Conclusion . Subjects receiving the combination of exercise and education and who complied with the treatment protocol improved their perceived ability to cope with other symptoms . In addition , a supervised exercise program increased walking distance at post-test , an increase that was maintained at followup in the exercise-only group . Results demonstrate the challenges with conducting exercise and education studies in persons with FM", "Objective . To follow patients with fibromyalgia six and 24 months after they finished a six-month treatment programme . The programme comprised pool exercise therapy , adjusted to the patients ' limitations , and education based on their health problems . Methods . Twenty-six patients were examined six and 24 months after the completion of the treatment programme with the Fibromyalgia Impact Question naire ( FIQ ) , SF-36 , the 6-minute walk test , and the Grippit measure . The values obtained at the follow-up examinations were compared with the baseline and post-treatment values . Results . As compared with baseline , symptom severity ( FIQ , SF-36 ) , physical function ( FIQ , SF-36 , 6-minute walk test ) and quality of life ( SF-36 ) still showed improvements six months after the completion of treatment ( p Pain ( FIQ , SF-36 ) , fatigue ( FIQ , SF-36 ) , walking ability , and social function ( SF-36 ) still showed improvements 2 years after the completion of the programme as compared with the baseline values ( p symptom severity , physical function and social function were still found six and 24 months after the completed treatment programme", "Objective The aim of this study was to compare pool-based exercise and balneotherapy in fibromyalgia syndrome ( FMS ) patients . Methods Fifty female patients diagnosed with FMS according to the American College of Rheumatism ( ACR ) criteria were r and omly assigned to two groups : group 1 ( n=25 ) with pool-based exercise , and in group 2 ( n=25 ) balneotherapy was applied in the same pool without any exercise for 35 min three times a week for 12 weeks . In both groups , pre- ( week 0 ) and post-treatment ( weeks 12 and 24 ) evaluation was performed by one of the authors , who was blind to the patient group . Evaluation parameters included pain , morning stiffness , sleep , tender points , global evaluation by the patient and the physician , fibromyalgia impact question naire , chair test , and Beck depression inventory . Statistical analysis was done on data collected from three evaluation stages . Results Twenty-four exercise and 22 balneotherapy patients completed the study . Pretreatment ( week 0 ) measurements did not show any difference between the groups . In group 1 , statistically significant improvement was observed in all parameters ( P chair test at both weeks 12 and 24 . In group 2 , week 12 measurements showed significant improvement in all parameters ( P chair test and Beck depression inventory . Week 24 evaluation results in group 2 showed significant improvements in pain and fatigue according to visual analogue scale ( VAS ) , 5-point scale , number of tender points , algometric and myalgic scores , and patient and physician global evaluation ( P morning stiffness , sleep , fibromyalgia impact question naire ( FIQ ) , chair test , and Beck depression inventory parameters in this group . Comparison of the two groups based on the post-treatment ( weeks 12 and 24 ) percent changes and difference scores relative to pretreatment ( week 0 ) values failed to show a significant difference between the groups for any parameter except Beck depression inventory ( P pool-based exercise had a longer-lasting effect on some of the FMS symptoms , but statistical analysis failed to show a significant superiority of pool-based exercise over balneotherapy without exercise . While we believe that exercise is a gold st and ard in FMS treatment , we also suggest in light of our results that balneotherapy is among the valid treatment options in FMS , and further research regarding the type and duration of the exercise programs is necessary", "OBJECTIVE To evaluate the short- and long-term efficacy of exercise therapy in a warm , waist-high pool in women with fibromyalgia . METHODS Thirty-four women ( mean + /- SD tender points 17 + /- 1 ) were r and omly assigned to either an exercise group ( n = 17 ) to perform 3 weekly sessions of training including aerobic , proprioceptive , and strengthening exercises during 12 weeks , or to a control group ( n = 17 ) . Maximal unilateral isokinetic strength was measured in the knee extensors and flexors in concentric and eccentric actions at 60 degrees /second and 210 degrees /second , and in the shoulder abductors and adductors in concentric contractions . Health-related quality of life ( HRQOL ) was assessed using the EQ-5D question naire ; pain was assessed on a visual analog scale . All were measured at baseline , posttreatment , and after 6 months . RESULTS The strength of the knee extensors in concentric actions increased by 20 % in both limbs after the training period , and these improvements were maintained after the de-training period in the exercise group . The strength of other muscle actions measured did not change . HRQOL improved by 93 % ( P = 0.007 ) and pain was reduced by 29 % ( P = 0.012 ) in the exercise group during the training , but pain returned close to the pretraining level during the subsequent de-training . However , there were no changes in the control group during the entire period . CONCLUSION The therapy relieved pain and improved HRQOL and muscle strength in the lower limbs at low velocity in patients with initial low muscle strength and high number of tender points . Most of these improvements were maintained long term", "OBJECTIVE To compare hydrotherapy ( HT ) and conventional physiotherapy ( CP ) in the treatment of fibromyalgia ( FM ) , regarding quality of life ( QOL ) , total sleep time ( TST ) , and total nap time ( TNT ) . METHODS Fifty out patients , all female , 30 - 60 years old , diagnosed with FM , were r and omly assigned to two groups to carry out 3 weeks of treatment with HT or CP . In the beginning and in the end of treatment , patients were evaluated with the SF-36 question naire to measure QOL and the sleep diary for TST and TNT . Data analyses were blind . RESULTS All 24 HT patients increased 1h in TST compared to 19 CP patients . TNT decreased in the HT group . QOL improved for the two groups in all domains when pre- and post-intervention were compared , but there was no difference between groups . CONCLUSION HT is more effective than CP to improve TST and to decrease TNT in FM patients", "OBJECTIVE To compare the therapeutic effects of physical fitness training or biofeedback training with the results of usual care in patients with fibromyalgia ( FM ) . METHODS One hundred forty-three female patients with FM ( American College of Rheumatology criteria ) were r and omized into 3 groups : a fitness program ( n = 58 ) , biofeedback training ( n = 56 ) , or controls ( n = 29 ) . Half the patients in the active treatment groups also received an educational program aim ed at improving compliance . Assessment s were done at baseline and after 24 weeks . The primary outcome was pain [ visual analog scale ( VAS ) ] . Other endpoints were the number of tender points , total myalgic score ( dolorimetry ) , physical fitness , functional ability ( Arthritis Impact Measurement Scale and Sickness Impact Profile ) , psychological distress ( Symptom Checklist-90-Revised ) , patient global assessment ( 5 point scale ) , and general fatigue ( VAS ) . RESULTS Baseline scores were similar in all 3 groups . Altogether 25 ( 17.5 % ) patients dropped out ; they were similarly distributed over all groups : 14 patients after r and omization and 11 ( 8 % ) during the study . A true high impact level for fitness training was not attained by any patient . After treatment , no significant differences in change scores of any outcome were found between the groups ( ANOVA , p > 0.05 ) . All outcome measures showed large variations intra- and interindividually . The educational program did not result in higher compliance with training sessions ( 62 % vs 71 % ) . Analysis of the subgroup of subjects with a high attendance rate ( > 67 % ) also showed no improvement . CONCLUSION In terms of training intensity and maximal heart rates , the high impact fitness intervention had a low impact benefit . Therefore effectiveness of high impact physical fitness training can not be demonstrated . Thus compared to usual care , the fitness training ( i.e. , low impact ) and biofeedback training had no clear beneficial effects on objective or subjective patient outcomes in patients with FM", "OBJECTIVE To compare the clinical effectiveness of aerobic exercise in the water with walking/jogging for women with fibromyalgia ( FM ) . METHODS Sixty sedentary women with FM , ages 18 - 60 years , were r and omly assigned to either deep water running ( DWR ) or l and -based exercises ( LBE ) . Patients were trained for 15 weeks at their anaerobic threshold . Visual analog scale of pain , Fibromyalgia Impact Question naire ( FIQ ) , Beck Depression Inventory , Short Form 36 Health Survey ( SF-36 ) , and a patient 's global assessment of response to therapy ( PGART ) were measured at baseline , week 8 , and week 15 . Statistical analysis included all patients . RESULTS Four patients dropped out from each group . Both groups improved significantly at week 15 compared with baseline , with an average 36 % reduction in pain intensity . For PGART , 40 % of the DWR group and 30 % of the LBE group answered \" much better \" at posttreatment . FIQ total score and FIQ depression improvements in the DWR group were faster ( week 8) than the LBE group and kept improving ( week 15 ; P improvements in SF-36 role emotional ( P = 0.006 ) . No significant between-group differences were observed for peak oxygen uptake and other outcomes . CONCLUSION DWR is a safe exercise that has been shown to be as effective as LBE regarding pain . However , it has been shown to bring more advantages related to emotional aspects . Aerobic gain was similar for both groups , regardless of symptom improvement . Therefore , DWR could be studied as an exercise option for patients with FM who have problems adapting to LBE or lower limbs limitations", "OBJECTIVE To evaluate the effect of exercise on mood and physical function in individuals with fibromyalgia . METHODS Subjects were r and omly assigned to an exercise ( EX ) or control ( CTL ) group . EX subjects participated in 3 30-minute exercise classes per week for 23 weeks . Subjects were tested at entry and at 6 , 12 , and 23 weeks . Tests included the Beck Depression Inventory ( BDI ) , 6-minute walk , State-Trait Anxiety Inventory ( STAI ) , Mental Health Inventory ( MHI ) , Fibromyalgia Impact Question naire ( FIQ ) , Arthritis Self-Efficacy Scale ( ASES ) , and a measure of tender points and knee strength . RESULTS Fifty subjects ( 27 EX , 23 CTL ) completed the study , and 31 ( 15 EX , 16 CTL ) met criteria for efficacy analyses . In efficacy analyses , significant improvements were seen for EX subjects in 6-minute walk distances , BDI ( total , cognitive/ affective ) , STAI , FIQ , ASES , and MHI ( 3 of 5 subscales ) scores . These effects were reduced but remained during intent-to-treat analyses . CONCLUSION Exercise can improve the mood and physical function of individuals with fibromyalgia", "OBJECTIVE To assess the responsiveness of the Fibromyalgia Impact Question naire ( FIQ ) , patient ratings of pain intensity , number of tender points , and total tender point pain intensity score to perceived changes in clinical status in patients with fibromyalgia ( FM ) . METHODS Using data from a r and omized placebo controlled study evaluating efficacy of magnetic therapy in patients with FM , the ability of primary outcomes to detect clinical ly meaningful changes over a 6 month period was assessed by : ( 1 ) degree of association between outcome change scores and patient global ratings of symptom change ( Spearman rank-order correlations ) ; ( 2 ) ability of these scores to discriminate among groups of patients whose perceived health status had changed to varying degrees ( ANOVA ) ; ( 3 ) ability of these scores , individually and jointly , to discriminate between patients who had reported improvement and those who did not ( logistic regression ) ; ( 4 ) effect size , st and ardized response mean , and Guyatt 's statistic were calculated to quantify responsiveness . RESULTS Correlations showed the outcome measures were moderately responsive to perceived symptomatic change . For FIQ , pain intensity ratings and number of tender points , differences in change scores between globally improved and unchanged groups and between globally improved and worsened groups were significant ; for total tender point pain intensity , the globally improved differed from worsened group . FIQ outperformed the other measures in discriminating between patients who reported improvement from those who did not . Summary statistics were consistent with discriminatory analyses , indicating the measures were sensitive to improvement , but relatively unresponsive to decline . CONCLUSION The FIQ was the most responsive measure to perceived clinical improvement and we recommend its inclusion as a primary endpoint in FM clinical trials", "Objective : The aim of the present study is to evaluate the effectiveness of spa therapy in the management of fibromyalgia . Methods : Thirty women with fibromyalgia were r and omly assigned to either a spa therapy group or a control group . The spa therapy group ( n = 16 ) had spa treatment for 2 weeks in addition to their medical treatment . The control group ( n = 14 ) continued to have their medical treatment and /or daily exercises . An investigator who was blinded for the intervention assessed all the patients for 9 months . Improvements in Fibromyalgia Impact Question naire ( FIQ ) , pain and number of tender points were primary outcomes . Secondary outcome measures were improvement in sleep disturbance , fatigue , gastrointestinal symptoms , anxiety , Beck Depression Inventory and patient ’s global evaluation . Results : the spa group was found to be superior to the control group at the end of intervention in terms of FIQ , pain , tender point count , fatigue and patients ’ global assessment . This superiority remained for 6 months in FIQ , 1 month in pain and tender point count . Conclusion : It was concluded that the addition of spa therapy to medical therapy has both short- and long-term beneficial effects in female patients with fibromyalgia", "Abstract . Fibromyalgia syndrome ( FMS ) is a very common rheumatological diagnosis . There are various treatment modalities . This study was planned to investigate the effects of balneotherapy in the treatment of FMS . A total of 42 primary fibromyalgia patients diagnosed according to American College of Rheumatology criteria were included in the study . Their ages ranged between 30 and 55 years . Patients were r and omly assigned to two groups . None of them had had a cardiovascular disease before . Group 1 ( n=22 ) received 20-min bathing , once a day and five times per week . Patients participated in the study for 3 weeks ( total of 15 sessions ) . Group 2 ( n=20 ) was accepted as the control group . Patients were evaluated by the number of tender points , Visual Analogue Scale for pain , Beck 's Depression Index for depression , and Fibromyalgia Impact Question naire for functional capacity . Measurements were assessed initially , after the therapy , and at the end of the 6th month . In group 1 , there were statistically significant differences in numbers of tender points , Visual Analogue scores , Beck 's Depression Index , and Fibromyalgia Impact Question naire scores after the therapy program ( P number of tender points ( P Visual Analogue scores , and Fibromyalgia Impact Question naire ( P Beck 's Depression Index scores compared to the control group ( P>0.05 ) . Patients with FMS mostly complain about pain , anxiety , and the difficulty in daily living activities . This study shows that balneotherapy is effective and may be an alternative method in treating fibromyalgia patients", "BACKGROUND Balneotherapy has been successfully used to treat various rheumatic diseases , but has only recently been evaluated for the treatment of fibromyalgia . Since no effective treatment exists for this common rheumatic disease , complementary methods of treatment have been attempted . OBJECTIVES To assess the effectiveness of balneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis . METHODS Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of balneotherapy at the Dead Sea area . Clinical indices assessed were duration of morning stiffness , number of active joints , a point count of 18 fibrositic tender points , and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter . RESULTS The number of active joints was reduced from 18.4 + /- 10.9 to 9 + /- 8.2 ( P number of tender points was reduced from 12.6 + /- 2 to 7.1 + /- 5 in men ( P dolorimetric threshold readings after the treatment period in women ( P number of active joints and the reduction in the number of tender points in the same patients ( r = 0.2 ) . CONCLUSIONS Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis . Further research is needed to eluci date the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population" ]

[ "BACKGROUND Amiodarone use was associated with an increased need for pacemaker insertion in a retrospective study of patients with atrial fibrillation ( AF ) and prior myocardial infa rct ion . The aims of this study were to determine prospect ively whether amiodarone increases the need for pacemakers in a general population of patients with AF and whether this effect is modified by sex . METHODS The study included 1005 patients with new-onset AF who were enrolled in the Fibrillation Registry Assessing Costs , Therapies , Adverse events , and Lifestyle ( FRACTAL ) . Multivariable Cox regression models , including time-dependent covariates accounting for medication exposure , were used to evaluate the risk of pacemaker insertion associated with amiodarone use . RESULTS Amiodarone use was associated with an increased risk of pacemaker insertion ( hazard ratio [ HR ] , 2.01 ; 95 % confidence interval [ CI ] , 1.08 - 3.76 ) after adjustment for age , sex , atrial flutter , coronary artery disease , heart failure , and hypertension . The effect of amiodarone use was modified by sex , with a significant risk in women but not in men ( HR , 4.69 ; 95 % CI , 1.99 - 11.05 vs HR , 1.05 ; 95 % CI , 0.42 - 2.58 [ P = .02 ] ) . This interaction remained significant after adjustment for weight , body mass index , weight-adjusted amiodarone dose , and use of other antiarrhythmic or rate control drugs . CONCLUSION The risk of bradyarrhythmia requiring pacemaker insertion associated with amiodarone use for AF is significantly greater in women than in men , independent of weight or body mass index", "Patients with atrial fibrillation ( AF ) report impaired health-related quality of life ( QOL ) . Differences between men and women with AF have not been described and personality attributes such as somatization ( tendency to amplify benign bodily sensations ) may mediate potential gender differences in QOL . Patients with AF ( n = 264 , 59 % men ) who participated in the Canadian Trial of Atrial Fibrillation ( n = 403 ) completed vali date d QOL question naires at baseline , 3 months , and 12 months after antiarrhythmic drug treatment . Women were significantly older than men and a greater proportion had hypertension , but other cardiac variables did not differ between women and men . At baseline , after controlling for significant clinical and demographic factors , women reported worse physical health ( p = 0.002 ) and functional capacity ( p mental health or general well-being . Women also had more frequent and severe cardiac symptoms than men ( both p Physical health improved significantly from baseline to 3 months for women ( p = 0.002 ) , but not for men ( p = 0.066 ) . Conversely , mental health improved for men ( p = 0.007 ) , but not for women . Cardiac symptom frequency and severity improved over time for women and men ( all p poor QOL , and women had higher scores than men ( p = 0.023 ) . However , after controlling for somatization , women still had worse physical function , functional capacity , and symptom burden than men . Independent of cardiac disease severity and age , women with AF had significantly more impaired QOL than men , specifically on domains related to physical rather than emotional functioning . Personality attributes may have a role in influencing QOL outcomes", "BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin . METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P hypertension ( RR=2.0 , P systolic blood pressure > 160 mm Hg ( RR=2.3 , P prior stroke or transient ischemic attack ( RR=2.9 , P stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation", "BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P dabigatran ( P mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage . Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 .", "BACKGROUND Most of the published research on atrial fibrillation ( AF ) is limited to studies in the developed world and included mainly Caucasian patients . Data about women with AF among other ethnicities is very limited . OBJECTIVES The aim of this study was to compare the clinical characteristics , treatment and outcome of women to men hospitalized with AF in a middle-eastern country . METHODS Retrospective analysis of prospect i ve registry of all patients hospitalized with AF in Qatar from 1991 through 2010 was made . Clinical characteristics , management , and outcomes of AF patients were compared according to gender . RESULTS During the 20-years period ; 1417 women and 2432 men were hospitalized for AF . Women were 5 years older and more likely to have diabetes mellitus , hypertension , and chronic renal impairment and were also less likely to be current smokers and to have ischemic heart disease and impaired left ventricular function when compared to men . There was no gender preference in the use of anticoagulation . The prevalence of concomitant ischemic heart disease and hypertension increased , while the prevalence of valvular heart disease and heart failure decreased among patients hospitalized with AF over the study period . In-hospital mortality and stroke rates were comparable between the two groups . CONCLUSIONS Women hospitalized with atrial fibrillation were older in age and had higher prevalence of co-morbid cardiovascular risk factors compared to men whereas , mortality and stroke rates were comparable", "AIMS Women have an increased risk for atrial fibrillation (AF)-related complications and there is evidence towards a reduced efficacy of the rhythm control strategy than men . A catheter-based strategy is therefore widely attractive , but the impact of gender on catheter ablation ( CA ) of AF remains undefined . METHODS AND RESULTS We included 221 consecutive patients ( 150 men ) who underwent CA of drug-refractory AF . Gender differences in clinical presentation and outcomes were compared . Women were older ( P = 0.002 ) , had a longer history of AF ( P = 0.04 ) , and were more likely to have hypertension ( P = 0.04 ) . Moreover , a concomitant valvular heart disease tended to be more common in women ( 32.4 vs. 23.3 % ; P = 0.28 ) and left atrium dimensions were significantly larger ( P = 0.003 ) . However , acute success rate and complications rate were similar between genders . After 22.5 + /- 11.8 months of follow-up , the overall freedom from arrhythmia recurrences was similar ( 83.1 vs. 82.7 % in men ) , and a similar improvement in SF-36 quality of life scores was achieved in both groups . CONCLUSION Women are referred for AF ablation later with a more complex clinical pre-operative presentation . Despite this higher risk profile in women , no differences were detected in clinical outcomes . Our findings indicate that CA of AF appears to be safe and effective in women as in men", "Background —Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ) . We examined data from a large contemporary cohort of AF patients to address this question . Methods and Results —We prospect ively studied 13 559 adults with AF and recorded data on patients ’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke , peripheral embolism , and major hemorrhagic events through search ing vali date d computerized data bases and medical record review . We compared event rates by patient sex using multivariable log-linear regression , adjusting for clinical risk factors for stroke , and stratifying by warfarin use . We identified 394 ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin . After multivariable analysis , women had higher annual rates of thromboembolism off warfarin than did men ( 3.5 % versus 1.8 % ; adjusted rate ratio [ RR ] , 1.6 ; 95 % CI , 1.3 to 1.9 ) . There was no significant difference by sex in 30-day mortality after thromboembolism ( 23 % for both ) . Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men ( RR , 0.4 ; 95 % CI , 0.3 to 0.5 ; and RR , 0.6 ; 95 % CI , 0.5 to 0.8 , respectively ) , with similar annual rates of major hemorrhage ( 1.0 % and 1.1 % , respectively ) . Conclusions —Women are at higher risk than men for AF-related thromboembolism off warfarin . Warfarin therapy appears be as effective in women , if not more so , than in men , with similar rates of major hemorrhage . Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF", "AIMS The risk of stroke is greater among women with atrial fibrillation ( AF ) than men . Warfarin protects against stroke , but treatment-related bleeding occurs more often in women than in men . METHODS AND RESULTS SPORTIF III ( open label , n=3410 ) and V ( double-blind , n=3922 ) included 2257 women with AF and one or more stroke risk factors r and omized to warfarin [ target international normalized ratio ( INR ) 2.0 - 3.0 ] or ximelagatran ( 36 mg twice daily ) . Primary outcomes were all stroke ( ischaemic/haemorrhagic ) and systemic embolic event . Women were older , on average , than men , 73.4+/-8.0 vs. 69.8+/-9.0 years ( P ) . More women were > 75-years old and women had more risk factors than men had ( P INR on warfarin ( mean 2.5+/-0.7 ) was within target range for 67 % of follow-up regardless of gender . Women more often developed primary events [ 2.08%/year , 95 % confidence interval ( CI ) 1.60 - 2.56%/year vs. 1.44%/year , 95 % CI 1.18 - 1.71%/year in men ; P=0.016 ) . Major bleeding rates were similar ( P=0.766 ) but women experienced more overall ( major/minor ) bleeding ( P Warfarin was associated with more overall bleeding in both genders and more major bleeding in women than in men ( P=0.001 ) . CONCLUSION When compared with men with AF , women in these studies were older and had more stroke risk factors . Women were more prone to anticoagulant-related bleeding ; the higher rate of thrombo-embolism among women was related to more frequent interruption of anticoagulant therapy", "Arrhythmias in women may be affected by phases of the menstrual cycle . This study was design ed to determine the prevalence of perimenstrual clustering of spontaneous episodes of paroxysmal supraventricular tachycardia ( SVT ) in women . It also tested the hypothesis that women with this temporal pattern of events have an altered probability of induction of paroxysmal SVT during electrophysiologic testing at higher estrogen states ( midcycle or with estrogen replacement therapy ) than at low estrogen states ( perimenstrual or without estrogen replacement ) . A structured history of the relation of spontaneous paroxysmal SVTs to phases of the menstrual cycle was obtained prospect ively among 42 women referred during a 3-year period . Patients with cyclical patterns of spontaneous tachycardias , who had had negative electrophysiologic studies at midcycle or while receiving estrogen replacement therapy , had repeat procedures ( 1 ) when premenstrual or at the onset of menses , or ( 2 ) after stopping estrogen replacement therapy . Seventeen of 42 consecutive female patients ( 40 % ) had histories of perimenstrual clustering of arrhythmias . Six women ( 4 with normal menstrual cycles , 2 on estrogen replacement therapy ) , who qualified for paired electrophysiologic studies because of a negative initial electrophysiologic study that included provocation with isoproterenol , had inducibility into SVTs during the second study . All 6 had dual atrioventricular ( AV ) nodal pathway physiology , 4 had AV nodal reentrant tachycardia ( AVNRT ) induced , 1 had both AVNRT and reciprocating AV tachycardias , and 1 had nonsustained AVNRT and an atrial tachycardia induced . Successful ablation procedures were performed in 5 of the 6 patients . Thus , among women with a history of perimenstrual clustering of paroxysmal SVT and among those receiving estrogen replacement therapy , scheduling of elective electrophysiologic procedures at times of low estrogen levels ( premenstrual or off estrogen replacement therapy ) may facilitate the probability of a successful procedure", "OBJECTIVES It is uncertain whether gender affects the outcomes of catheter ablation ( CA ) for atrial fibrillation ( AF ) . The objective of the study is to evaluate the efficacy and safety of CA for long-st and ing persistent AF in women . METHODS Between January 2010 and May 2011 , 220 consecutive patients ( 73 females , 33.2 % ) , with long-st and ing persistent AF who underwent CA were prospect ively recruited . Gender-related differences in clinical presentation , periprocedural complications , and outcomes were compared . RESULTS Women were less likely to have lone AF than men ( 27.4 % vs 47.6 % ; P = 0.004 ) . The incidence of rheumatic heart disease was higher in women ( 19.2 % in women vs 1.4 % in men ; P initial ablation success rate than men ( 35.6 % vs 57.1 % ; P = 0.003 ) . Hematomas occurred more often in women ( 6.8 % in women vs 0.7 % in men ; P = 0.027 ) . A Cox regression analysis demonstrated total duration of AF ( per month , hazard ratio [ HR ] 1.003 , confidence interval [ CI ] 1.001 - 1.006 ; P = 0.006 ) and gender ( HR 1.663 , CI 1.114 - 2.485 ; P = 0.013 ) as the independent predictors for recurrence after the first CA . CONCLUSIONS Women and long AF duration were closely related to the recurrence of AF after the first ablation in patients with long-st and ing persistent AF . Women also had a higher risk of vascular complications", "BACKGROUND The impact of atrial fibrillation ( AF ) on mortality , stroke , and medical costs is unknown . METHODS We conducted a prospect i ve cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis ( CVD ) compared with a matched group without AF ( n = 26,753 ) , r and omly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF . Stroke rates were also determined in another cohort free of CVD ( n = 14,267 ) . Total medical costs after hospitalization were available from a 1991 cohort . Cumulative mortality , stroke rates , and costs following index admission were adjusted by multivariate and proportional hazard regression analyses . RESULTS Mortality rates were high in individuals with CVD , ranging from 19.0 % to 52.1 % in 1 year . Adjusted relative mortality risk was approximately 20 % higher in patients with AF in all age-sex strata during each of the 3 years studied ( P Incidence of stroke was high in individuals with CVD , 6.2 % to 15.4 % in 1 year , with and without AF , and was at least 5-fold higher than in individuals without CVD . In those with CVD , stroke rates were approximately 25 % higher in women with AF ( P Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men , and 9.8- to 11.2-fold greater in women with AF ( P Second- and third-year costs were increased as well . CONCLUSION Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs", "OBJECTIVES This study examined the risk of proarrhythmic events in patients receiving antiarrhythmic drugs for treatment of atrial fibrillation ( AF ) according to present-day safety guidelines . BACKGROUND Advances in underst and ing the proarrhythmic risk of antiarrhythmic drugs has led to development of safety guidelines for these agents . Such guidelines were used in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . METHODS This study was an analysis of the risk of arrhythmic events ( arrhythmic death , resuscitated cardiac arrest , sustained ventricular tachycardia ( VT ) , and torsade de pointes VT ) in the antiarrhythmic drug arm of the AFFIRM study . Each time an antiarrhythmic drug was begun , it was counted as an exposure to that drug and the risk of an arrhythmic event was calculated . RESULTS A total of 2,033 patients received 3,030 exposures to antiarrhythmic drugs . Ninety-six arrhythmic events occurred by six years . Patients with a left ventricular ejection fraction arrhythmic events . Twelve documented cases of torsade de pointes VT were noted . The incidence of torsade de pointes was 0.6 % at five years ( 95 % confidence interval 0.32 to 1.07 ) . CONCLUSIONS The overall risk of adverse arrhythmic events upon exposure to antiarrhythmic drugs in the AFFIRM study was reasonably low . Strict criteria for the safe use of antiarrhythmic drugs were successful in minimizing proarrhythmic events", "The efficacy of adjusted-dose oral anticoagulant treatment ( OAT ) in the prevention of stroke in atrial fibrillation ( AF ) is well documented . Available data show that AF patients are widely heterogeneous in terms of ischaemic stroke risk . The role of female gender as a predictor of stroke risk is inconsistent , in particular it is unclear if warfarin treatment is able to prevent stroke equally in both sexes . We performed a prospect i ve study on 780 AF patients on OAT , followed by an Anticoagulation Clinic , to evaluate if female gender is a risk factor for stroke among patients on OAT and if the quality of anticoagulation is different between genders . No difference was found in relation to the quality of anticoagulation between genders ( p=0.5 ) . During follow-up 33 patients had major bleedings ( rate 1.37 x 100 pt/yrs ) but no difference was found between genders in bleeding risk . Forty patients had ischaemic events [ rate 1.66 x 100 pt/yrs ; males rate 1.2 x 100 pt/yrs ; females rate 2.43 x 100 pt/yrs ; p=0.042 ; relative risk ( RR ) of females vs. males 2.0 ( 95 % confidence interval [ CI ] 1.3 - 3.1 ) ; p= 0.004 ] . The higher rate of ischaemic events in females with respect to males was confirmed at Cox regression analysis after correction for age ( p=0.009 ) . In addition , strokes occurring in females were more disabling , and RR for severe and fatal stroke , defined according to Modified Rankin scale , of females vs. males was 3.1 ( 95 % CI 1.3 - 6.5 ; p=0.001 ) . In conclusion , our data show a higher risk of stroke in anticoagulated AF females with respect to males , despite a similar quality of anticoagulation", "BACKGROUND The impact of atrial fibrillation ( AF ) and its treatment on health-related quality of life ( QOL ) is not well understood . We assessed QOL in patients with symptomatic AF participating in the Canadian Trial of Atrial Fibrillation . METHODS Self-report QOL question naires including the Short-Form-36 ( SF-36 ) , symptom checklist ( SCL ) and AF Severity Scale ( AFSS ) were completed at baseline and 3 , and 12 months after r and omization . RESULTS The study group was aged 65 + /- 10 years and 59 % were male . By design , 50 % of patients were r and omized to amiodarone ( n = 132 ) , 25 % to sotalol ( n = 66 ) , and 25 % to propafenone ( n = 66 ) . Most patients had normal left ventricular function ( 89 % ) . Physical ( 41.9 + /- 9.3 to 43.7 + /- 9.2 , P = .001 ) and mental health ( 47.5 + /- 10.5 to 49.0 + /- 9.8 , P = .023 ) summary measures from the SF-36 improved significantly from baseline to 3 months . Arrhythmia symptom frequency and severity ( SCL ) also improved markedly from baseline to 3 months ( symptom frequency 20.4 + /- 9.4 to 16.2 + /- 9.5 and symptom severity 16.7 + /- 8.2 to 12.9 + /- 7.4 , both P QOL improvements were not significantly different among the groups r and omized to amiodarone , sotalol , or propafenone . However , patients with no symptomatic recurrences of AF had higher scores at 3 months on measures of global well-being than those with recurrences in the first 3 months ( 7.4 + /- 1.8 vs 6.9 + /- 1.8 , P QOL changes from the 3 to 12 month assessment . CONCLUSION In patients with symptomatic AF , QOL improves after treatment , independent of the specific drug used for treatment . This is especially true for patients in whom treatment prevents AF recurrence", "CONTEXT Prior risk stratification schemes for atrial fibrillation ( AF ) have been based on r and omized trial cohorts or Medicare administrative data bases , have included patients with established AF , and have focused on stroke as the principal outcome . OBJECTIVE To derive risk scores for stroke alone and stroke or death in community-based individuals with new-onset AF . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , community-based , observational cohort in Framingham , Mass. We identified 868 participants with new-onset AF , 705 of whom were not treated with warfarin at baseline . Risk scores for stroke ( ischemic or hemorrhagic ) and stroke or death were developed with censoring when warfarin initiation occurred during follow-up . Event rates were examined in low-risk individuals , as defined by the risk score and 4 previously published risk schemes . MAIN OUTCOME MEASURES Stroke and the combination of stroke or death . RESULTS During a mean follow-up of 4.0 years free of warfarin use , stroke alone occurred in 83 participants and stroke or death occurred in 382 participants . A risk score for stroke was derived that included the following risk predictors : advancing age , female sex , increasing systolic blood pressure , prior stroke or transient ischemic attack , and diabetes . With the risk score , 14.3 % of the cohort had a predicted 5-year stroke rate stroke rate Actual stroke rates in these low-risk groups were 1.1 and 1.5 per 100 person-years , respectively . Previous risk schemes classified 6.4 % to 17.3 % of subjects as low risk , with actual stroke rates of 0.9 to 2.3 per 100 person-years . A risk score for stroke or death is also presented . CONCLUSION These risk scores can be used to estimate the absolute risk of an adverse event in individuals with AF , which may be helpful in counseling patients and making treatment decisions", "BACKGROUND Anticoagulants are effective in the prevention of stroke in atrial fibrillation and flutter ( AF ) . We aim ed to find out the prevalence of AF in the UK and to estimate the proportion of patients with AF who might benefit from anticoagulation . METHODS We screened with electrocardiography a r and om sample of 4843 people from the community aged 65 years and older for AF . Participants with AF had further investigations to identify risk factors for stroke and contraindications to anticoagulants . We used three sets of criteria to assess risk and eligibility for anticoagulation . FINDINGS 228 ( 4.7 % ) participants had AF . According to analyses derived from risk stratifications based on the Stroke Prevention in Atrial Fibrillation ( SPAF ) study 61 % of these patients would have benefited from anticoagulation , 49 % according to pooled analysis of trial results , and 41 % according to the inclusion criteria for the SPAF 3 study . Anticoagulants were used by 1114 ( 23 % ) of all patients and were least used among elderly women , who may be the most likely to benefit . Echocardiography would be useful to assess the need for anticoagulation only in patients younger than 75 years with no contraindications to treatment and no clinical risk factors for stroke . INTERPRETATION Anticoagulants seem to be underused and misdirected in treatment of AF , according to various criteria . Efforts to promote and support wider and more appropriate use of anticoagulants would seem to be justified , and should decrease the incidence of stroke amongst elderly patients", "Treatment guidelines for atrial fibrillation ( AF ) used in Western countries describe female gender as a risk factor for thromboembolic events in patients with nonvalvular AF ( NVAF ) . The present study aim ed to determine the impact of gender on prognosis of Japanese patients with NVAF . A sub analysis of 7,406 patients with NVAF ( mean age 70 years ) who were followed-up prospect ively for 2 years was performed using data from the J-RHYTHM registry . The primary end points were thromboembolic events , major hemorrhaging , total mortality , and cardiovascular mortality . Compared with male subjects ( n = 5,241 ) , female subjects ( n = 2,165 ) were older and displayed greater prevalences of paroxysmal AF , heart failure , and hypertension but less prevalences of diabetes , previous cerebral infa rct ion , and coronary artery disease . Male and female patients had mean CHADS2 ( Congestive heart failure , Hypertension , Age of 75 years or more , Diabetes mellitus and prior Stroke or transient ischemic attack ) scores of 1.6 and 1.8 , respectively ( p Warfarin was given to 87 % of male patients and 86 % of female patients ( p = 0.760 ) , and the 2 genders displayed similar mean international normalized ratio of prothrombin time values at baseline ( 1.91 vs 1.90 , respectively , p = 0.756 ) . Multivariate logistic regression analysis indicated that male gender was an independent risk factor for major hemorrhaging ( odds ratio 1.59 , 95 % confidence interval 1.05 to 2.40 , p = 0.027 ) and all-cause mortality ( odds ratio 1.78 , 95 % confidence interval 1.25 to 2.55 , p thromboembolic events ( odds ratio 1.24 , 95 % confidence interval 0.83 to 1.86 , p = 0.297 ) or cardiovascular mortality ( odds ratio 0.96 , 95 % confidence interval 0.56 to 1.66 , p = 0.893 ) . In conclusion , female gender is not a risk factor for thromboembolic events among Japanese patients with NVAF who were treated mostly with warfarin . However , male gender is a risk factor for major hemorrhaging and all-cause mortality", "BACKGROUND Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations . Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin . METHODS In this r and omized , double-blind trial , we compared apixaban ( at a dose of 5 mg twice daily ) with warfarin ( target international normalized ratio , 2.0 to 3.0 ) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke . The primary outcome was ischemic or hemorrhagic stroke or systemic embolism . The trial was design ed to test for noninferiority , with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause . RESULTS The median duration of follow-up was 1.8 years . The rate of the primary outcome was 1.27 % per year in the apixaban group , as compared with 1.60 % per year in the warfarin group ( hazard ratio with apixaban , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.95 ; P rate of major bleeding was 2.13 % per year in the apixaban group , as compared with 3.09 % per year in the warfarin group ( hazard ratio , 0.69 ; 95 % CI , 0.60 to 0.80 ; P rates of death from any cause were 3.52 % and 3.94 % , respectively ( hazard ratio , 0.89 ; 95 % CI , 0.80 to 0.99 ; P=0.047 ) . The rate of hemorrhagic stroke was 0.24 % per year in the apixaban group , as compared with 0.47 % per year in the warfarin group ( hazard ratio , 0.51 ; 95 % CI , 0.35 to 0.75 ; P rate of ischemic or uncertain type of stroke was 0.97 % per year in the apixaban group and 1.05 % per year in the warfarin group ( hazard ratio , 0.92 ; 95 % CI , 0.74 to 1.13 ; P=0.42 ) . CONCLUSIONS In patients with atrial fibrillation , apixaban was superior to warfarin in preventing stroke or systemic embolism , caused less bleeding , and result ed in lower mortality . ( Funded by Bristol-Myers Squibb and Pfizer ; ARISTOTLE Clinical Trials.gov number , NCT00412984 . )", "UNLABELLED The influence of age and gender on the character of paroxysmal atrial fibrillation ( PAD ) has not been described . METHODS The heart rate ( HR ) during PAF in patients receiving placebo or antiarrhythmic therapy was analyzed . Data from 177 24-hour Holter recordings were analyzed to mark the onset and termination of PAF and converted into RR interval files . PAF episodes lasting at least 2 minutes and containing HR during the first 30-second segment versus during the remainder of the episode , and the duration of PAF episodes were compared among groups of different ages and sex ( Wilcoxon test ) . RESULTS 236 episodes from 55 recordings in 32 patients ( all patients : 61.4 + /- 12.8 years ; men ( 19 ) : 58.5 + /- 12.6 years ; women ( 13 ) 65.5 + /- 12.4 years , P = ns for difference in age ) fulfilled the inclusion criteria . Women had a higher mean heart rate at AF onset ( 123 + /- 35 beats/min vs 115 + /- 20 beats/min , P = 0.02 ) and during the remainder of the episode ( 120 + /- 25 beats/min vs 112 + /- 22 beats/min at the start , P = 0.01 , and 116 + /- 26 beats/min vs 108 + /- 18 beats/min subsequently , P = 0.01 ) . Episodes tended to be longer in women ( mean 89.8 min vs 50.5 min , P = NS ) and in the aged ( mean 83.8 min vs 46.9 min , P = NS ) . CONCLUSION PAF episodes are associated with faster heart rates and last longer in women , which may reflect differing autonomic responses to AF . A slower ventricular rate during PAF in older patients probably reflects an increasing prevalence of impaired atrioventricular conduction" ]

[ "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", "Four conventional glass-ionomer cements specifically developed for use with the atraumatic restorative treatment ( ART ) technique were compared with a resin-based sealant for marginal and surface dye penetration , material voids , and completeness of enamel fissure penetration . Thirty sound permanent m and ibular molar teeth were r and omly divided into five groups . After delayed placement of the glass-ionomer cement sealants using st and ardized finger pressure , and conventional placement of the resin-based sealant using a dental probe , the teeth were first thermocycled then the crowns immersed in methylene blue dye before being sectioned . There were no statistically significant differences found between any of the five material s , apart from less marginal dye leakage being present for the resin-based sealant than for one of the glass-ionomer cements . The cements , however , showed better fissure penetration than did the sealant . Despite the delayed placement and higher viscosity , all of the glass-ionomer cements showed satisfactory penetration of the enamel fissures and minimal marginal and surface dye penetration , and material voids , when placed using firm finger pressure . The cements could prove to be useful in the dental treatment of apprehensive children", "OBJECTIVES To measure the microtensile bond strength to ground enamel of different types of material s used as pit and fissure sealants in combination with different substrate conditioners . METHODS From 40 sound extracted molars , eight groups of five teeth were r and omly formed . The experimental groups were : ( 1 ) ( C ) 37 % phosphoric acid/ClinPro Sealant ( 3 M ESPE ) ; ( 2 ) ( G ) 37 % phosphoric acid/Guardian Seal ( Kerr ) ; ( 3 ) ( E/TF ) 37 % phosphoric acid/Excite/Tetric Flow ( Ivoclar-Vivadent ) ( 4 ) ( OS/UF ) 37 % phosphoric acid/One Step (Bisco)/UniFil Flow ( GC ) ; ( 5 ) ( OS/AE ) 37 % phosphoric acid/One Step/AEliteflo ( Bisco ) ; ( 6 ) ( UB/UF ) UniFil Bond/UniFil Flow ( GC ) ; ( 7 ) ( CC/FVII ) GC Cavity Conditioner/Fuji VII ( GC ) ; ( 8) ( CC/FII ) GC Cavity Conditioner/Fuji II LC Improved ( GC ) . On the buccal of each tooth , a 5 mm high build-up was created by incrementally adding layers of the sealing material on the conditioned enamel . By serially cutting the built-up tooth , multiple beam-shaped specimens about 1 mm x 1 mm in cross section were obtained , and loaded in tensile ( 0.5 mm/min ) until failure occurred . RESULTS The bond strengths measured in MPa were : ( C ) 20.41+/-11.79 ; ( G ) 16.02+/-7.99 ; ( E/TF ) 24.06+/-9.67 ; OS/UF 15.63+/-9.00 ; ( OS/AE ) 9.31+/-6.05 ; ( UB/UF ) 4.96+/-3.46 ; ( CC/FVII ) 1.70+/-2.19 ; ( CC/FII ) 2.19+/-1.44 . CONCLUSIONS The conventional and the resin-modified glass ionomers measured bond strengths significantly lower than those of any resin-based material s. Failure frequently occurred cohesively within the cement . Flowable composites in combination with phosphoric acid and a total-etch adhesive performed similarly to resin-based material s specifically conceived for sealings , such as ClinPro Sealant and Guardian Seal . The bond achieved by resin composite when treating enamel with the self-etching primer used in this study ( UniFil Bond ) was significantly lower than that developed when the substrate was etched with 37 % phosphoric acid", "Ideally , in view of rational practice management , the same GIC material may be used as a restorative material as well as a sealant material . The aim of this study is to compare the retention rates of a GIC design ed as sealant material ( Fuji Type IIIR , ) and a glass-ionomer restorative material ( Fuji Type IXR ) . In a clinical trial using a split mouth design , 104 children ( mean age 10.4 years , s.d . 1.2 ) of the Centre of Youth Dental Health Paramaribo ( Surinam ) received 208 sealants , 104 per material . The sealants were placed in upper or lower first or second molars by dental auxiliaries . Moisture control was achieved by cotton rolls . After four and nine months the retention of the sealants was checked clinical ly . For the evaluation at both times 99 molar pairs were available . After four months 46 percent of the Fuji IIIR and 72 percent of the Fuji IXR sealants showed complete retention . After nine months these percentages were 15 percent and 52 percent , respectively . In view of the study design , Relative Risks ( RR ) , and their 95 percent confidence intervals , were calculated . Converted to chance to total absence , the chance to absence of the material for Fuji IX was about 60 percent less than that for Fuji III ( four months RR = .44 ( .25 - .80 ) and nine months RR = .42 ( .39 - .45 ) ) . In conclusion the GIC restorative material showed to be more retentive then the GIC sealant material", "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" ]

[ "& NA ; This prospect i ve study was performed to investigate whether postoperative alternate flexion and extension splinting ( daily change in position of immobilization by splinting ) was useful in restoring full range of motion ( ROM ) after total knee arthroplasty as compared with continuous passive motion . The alternate flexion and extension splinting group and the continuous passive motion group were each composed of 34 knees . Final ROM was measured at an average of 3.5 years postoperatively . Squatting was possible in 31 knees ( 45.6 % ) of the alternate flexion and extension splinting group . The postoperative ROM of the osteoarthritic knees ( 131.8 ° ± 12.3 ° ) was significantly greater than that of the rheumatoid knees ( 121.9 ° ± 22.4 ° ) ( p The postoperative ROM of the alternate flexion and extension splinting group ( 135.1 ° ± 11.9 ° ) also was significantly greater than that of the continuous passive motion group ( 120.0 ° ± 19.7 ° ) ( p between the posterior slope of tibial cutting and the postoperative ROM . It is suggested that alternate flexion and extension splinting is effective in restoring full ROM after total knee arthroplasty", "PURPOSE This prospect i ve study aim ed to evaluate radiographically , mechanical or hip-knee-ankle ( HKA ) axis in healthy , asymptomatic , Asian ( Indian and Korean ) adults between 20 and 40 years of age to determine the incidence of inherent varus ( mechanical limb alignment of > 3 ° varus ) and the factors influencing it . METHODS Three hundred and eighty-eight lower limbs were evaluated using full length , st and ing hip-to-ankle radiographs in 198 healthy , asymptomatic , Asian ( Indian and Korean ) adults between 20 and 40 years of age to assess the hip-knee-ankle ( HKA ) angle , medial proximal tibial angle ( MPTA ) , femoral bowing and femoral neck-shaft angle to determine the incidence of inherent varus ( mechanical limb alignment of > 3 ° varus ) and the factors influencing it . RESULTS Overall , the mean HKA angle was 177.6 ° ±2.6 ° with 34.5 % of limbs in inherent varus ( mean HKA angle 174.9 ° ±1.8 ° ) . The incidence of inherent varus was significantly higher ( p=0.01 ) in males ( 40 % ) compared to females ( 28 % ) but similar among Indian ( 34 % ) and Korean subjects ( 35 % ) . The hip-knee-ankle ( HKA ) angle showed significant positive correlation ( r=0.82 , p the medial proximal tibial angle ( MPTA ) . CONCLUSIONS Inherent varus alignment of the lower limb is fairly common among asymptomatic , Asian adults . These results raise several pertinent questions regarding the role of inherent varus in the aetiopathogenesis of knee osteoarthritis and in lower limb realignment procedures", "We present the peak outcome results of the Oxford medial unicompartmental arthroplasty through a minimally invasive surgical incision . This prospect i ve study included 78 Oxford medial unicompartmental knee replacements in 68 patients . At the 2 year review the patients achieved a mean Oxford Knee Score of 38.3 . This was not significantly different to the 2 year results of the phase 2 Oxford knee carried out using a st and ard parapatellar approach when patients achieved a mean OKS of 36.0 . Four unicompartmental knee replacements required revision for unexplained pain , deep infection , aseptic loosening and bearing dislocation . Minimally invasive joint replacement is attractive to both patients and surgeons , but is technically dem and ing with complications inherent to limited access", "Aims Approved by the Food and Drug Administration in 2004 , the Phase III Oxford Medial Partial Knee is used to treat anteromedial osteoarthritis ( AMOA ) in patients with an intact anterior cruciate ligament . This unicompartmental knee arthroplasty ( UKA ) is relatively new in the United States , and therefore long-term American results are lacking . Patients and Methods This is a single surgeon , retrospective study based on prospect ively collected data , analysing a consecutive series of primary UKAs using the Phase III mobile-bearing Oxford Knee and Phase III instrumentation . Between July 2004 and December 2006 , the senior author ( RHE ) carried out a medial UKA in 173 patients ( 213 knees ) for anteromedial osteoarthritis or avascular necrosis ( AVN ) . A total of 95 patients were men and 78 were women . Their mean age at surgery was 67 years ( 38 to 89 ) and mean body mass index 29.87 kg/m2 ( 17 to 62 ) . The mean follow-up was ten years ( 4 to 11 ) . Results Survivorship of the Oxford UKA at ten years was 88 % , using life table analysis . Implant survivorship at ten years was 95 % . The most common cause for revision was the progression of osteoarthritis in the lateral compartment . The mean knee score element of the American Knee Society Score ( AKSS ) was 50 pre-operatively and increased to 93 post-operatively . The mean AKSS function score was 56 pre-operatively rising to 78 post-operatively Conclusion This ten-year follow-up study of the Oxford UKA undertaken in the United States shows good survivorship and excellent function in a wide selection of patients with AMOA and AVN . Cite this article : Bone Joint J 2016;98-B(10 Suppl B):34–40", "Aims The interest in unicompartmental knee arthroplasty ( UKA ) for medial osteoarthritis has increased rapidly but the long-term follow-up of the Oxford UKAs has yet to be analysed in non- design er centres . We have examined our ten- to 15-year clinical and radiological follow-up data for the Oxford Phase III UKAs . Patients and Methods Between January 1999 and January 2005 a total of 138 consecutive Oxford Phase III arthroplasties were performed by a single surgeon in 129 patients for medial compartment osteoarthritis ( 71 right and 67 left knees , mean age 72.0 years ( 47 to 91 ) , mean body mass index 28.2 ( 20.7 to 52.2 ) ) . Both clinical data and radiographs were prospect ively recorded and obtained at intervals . Of the 129 patients , 32 patients ( 32 knees ) died , ten patients ( 12 knees ) were not able to take part in the final clinical and radiological assessment due to physical and mental conditions , but via telephone interview it was confirmed that none of these ten patients ( 12 knees ) had a revision of the knee arthroplasty . One patient ( two knees ) was lost to follow-up . Results The mean follow-up was 11.7 years ( 10 to 15 ) . A total of 11 knees ( 8 % ) were revised . The survival at 15 years with revision for any reason as the endpoint was 90.6 % ( 95 % confidence interval ( CI ) 85.2 to 96.0 ) and revision related to the prosthesis was 99.3 % ( 95 % CI 97.9 to 100 ) . The mean total Knee Society Score was 47 ( 0 to 80 ) pre-operatively and 81 ( 30 to 100 ) at latest follow-up . The mean Oxford Knee Score was 19 ( 12 to 40 ) pre-operatively and 42 ( 28 to 55 ) at final follow-up . Radiolucency beneath the tibial component occurred in 22 of 81 prostheses ( 27.2 % ) without evidence of loosening . Conclusion This study supports the use of UKA in medial compartment osteoarthritis with excellent long-term functional and radiological outcomes with an excellent 15-year survival rate . Cite this article : Bone Joint J 2016;98-B(10 Suppl B):41–7", "The purpose of this study was to evaluate the mid‐term results of an Oxford phase‐3 unicompartmental knee arthroplasty ( UKA ) for medial arthritis in Chinese patients", "There are several surgical management options for medial knee arthritis , and it is often difficult to decide whether a unicompartmental knee arthroplasty ( UKA ) or total knee arthroplasty ( TKA ) is appropriate . Few studies have compared UKAs and TKAs in the same patient . We identified 23 patients with osteoarthritis who had a TKA on one side and a UKA on the other . The preoperative values of the 2 knees were not statistically different . Strict criteria were used to determine whether a UKA could be performed ( functional anterior cruciate ligament , minimal deformity , and minimum changes in other compartments ) . Preoperative radiographs were review ed to confirm that the knee undergoing TKA had medial compartment disease only . Knee Society scores , radiographic analysis , and patient preferences were recorded for all patients . Average follow-up was 46 months ( range , 7.2 - 148 months ) and 42 months ( range , 11.5 - 59.8 months ) for TKA and UKA , respectively . We found little or no difference in outcomes between the 2 procedures , except for an improved range of motion with the UKA compared with the TKA ( 123 degrees + /-9 degrees vs 119.8 degrees + /-7 degrees , respectively ) . Knee Society scores improved from 45.9 to 89.7 in UKA and from 42.4 to 90.3 in TKA . Of the 23 patients , 11 expressed no preference between either knee and 12 preferred the unicompartmental knee ; no patient preferred the total knee . With appropriate patient selection , UKAs are a successful option for patients with osteoarthritis", "There have been concerns about the long-term survival of unicompartmental knee arthroplasty ( UKA ) . This prospect i ve study reports the 15-year survival and ten-year functional outcome of a consecutive series of 1000 minimally invasive Phase 3 Oxford medial UKAs ( 818 patients , 393 men , 48 % , 425 women , 52 % , mean age 66 years ; 32 to 88 ) . These were implanted by two surgeons involved with the design of the prosthesis to treat anteromedial osteoarthritis and spontaneous osteonecrosis of the knee , which are recommended indications . Patients were prospect ively identified and followed up independently for a mean of 10.3 years ( 5.3 to 16.6 ) . At ten years , the mean Oxford Knee Score was 40 ( st and ard deviation ( sd ) 9 ; 2 to 48 ) : 79 % of knees ( 349 ) had an excellent or good outcome . There were 52 implant-related re-operations at a mean of 5.5 years ( 0.2 to 14.7 ) . The most common reasons for re-operation were arthritis in the lateral compartment ( 2.5 % , 25 knees ) , bearing dislocation ( 0.7 % , seven knees ) and unexplained pain ( 0.7 % , seven knees ) . When all implant-related re-operations were considered as failures , the ten-year rate of survival was 94 % ( 95 % confidence interval ( CI ) 92 to 96 ) and the 15-year survival rate 91 % ( CI 83 to 98 ) . When failure of the implant was the endpoint the 15-year survival was 99 % ( CI 96 to 100 ) . This is the only large series of minimally invasive UKAs with 15-year survival data . The results support the continued use of minimally invasive UKA for the recommended indications", "Medium-term survivorship of the Oxford phase 3 unicompartmental knee replacement ( UKR ) has not yet been established in an Asian population . We prospect ively evaluated the outcome of 400 phase 3 Oxford UKRs in 320 Korean patients with a mean age at the time of operation of 69 years ( 48 to 82 ) . The mean follow-up was 5.2 years ( 1 to 10 ) . Clinical and radiological assessment was carried out pre- and post-operatively . At five years , the mean Knee Society knee and functional scores had increased significantly from 56.2 ( 30 to 91 ) pre-operatively to 87.2 ( 59 to 98 ) ( p = 0.034 ) and from 59.2 ( 30 to 93 ) to 88.3 ( 50 to 100 ) ( p = 0.021 ) , respectively . The Oxford knee score increased from a mean of 25.8 ( 12 to 39 ) pre-operatively to 39.8 ( 25 to 58 ) at five years ( p = 0.038 ) . The ten-year survival rate was 94 % ( 95 % confidence interval 90.1 to 98.0 ) . A total of 14 UKRs ( 3.5 % ) required revision . The most common reason for revision was dislocation of the bearing in 12 ( 3 % ) . Conversion to a total knee replacement was required in two patients who developed osteoarthritis of the lateral compartment . This is the largest published series of UKR in Korean patients . It shows that the mid-term results after a minimally invasive Oxford phase 3 UKR can yield satisfactory clinical and functional results in this group of patients" ]

[ "INTRODUCTION Recent meta-analyses of the outcome of apical surgery using modern techniques including microsurgical principles and high-power magnification have yielded higher rates of healing . However , the information is mainly based on 1- to 2-year follow-up data . The present prospect i ve study was design ed to re-examine a large sample of teeth treated with apical surgery after 5 years . METHODS Patients were recalled 5 years after apical surgery , and treated teeth were classified as healed or not healed based on clinical and radiographic examination . ( The latter was performed independently by 3 observers ) . Two different methods of root-end preparation and filling ( primary study parameters ) were to be compared ( mineral trioxide aggregate [ MTA ] vs adhesive resin composite [ COMP ] ) without r and omization . RESULTS A total of 271 patients and teeth from a 1-year follow-up sample of 339 could be re-examined after 5 years ( dropout rate = 20.1 % ) . The overall rate of healed cases was 84.5 % with a significant difference ( P = .0003 ) when comparing MTA ( 92.5 % ) and COMP ( 76.6 % ) . The evaluation of secondary study parameters yielded no significant difference for healing outcome when comparing subcategories ( ie , sex , age , type of tooth treated , post/screw , type of surgery ) . CONCLUSIONS The results from this prospect i ve nonr and omized clinical study with a 5-year follow-up of 271 teeth indicate that MTA exhibited a higher healing rate than COMP in the longitudinal prognosis of root-end sealing", "OBJECTIVE R and omized clinical prospect i ve study to evaluate the application of MTA and IRM as retro grade sealers in surgical endodontics . STUDY DESIGN One hundred single-rooted teeth were surgically treated . After r and omization , MTA or IRM was used as a retrosealer . Radiographs were taken 1 week , 3 months , and 1 year postoperatively . Assessment was performed by 2 independent assessors 1 year after surgery . Both treatment groups were homogeneous in their composition , and clinical features and radiographic findings were classified according to Rud 's classification . RESULTS Complete healing was observed in 64 % of the MTA-treated teeth vs 50 % of the IRM-treated teeth . Incomplete healing was seen in 28 % ( MTA ) vs 36 % ( IRM ) , and unsatisfactory in 6 % ( MTA ) vs 14 % ( IRM ) . Only 1 failure was seen ( MTA ) . No statistically significant differences were found between the 2 retrofilling material s. CONCLUSION As root-end filling material s in this clinical prospect i ve r and omized design on single rooted teeth , MTA and IRM had the same clinical effectiveness", "INTRODUCTION This prospect i ve study examined the potential prognostic factors of endodontic microsurgery and compared the predictors of an isolated endodontic lesion with those of both an isolated endodontic lesion and an endodontic-periodontal lesion . METHODS Data were collected from the Microscope Center of the Department of Conservative Dentistry at the Dental College of Yonsei University , Seoul , Korea , between March 2001 and March 2011 . A total number of 584 teeth were included , and all clinical procedures were performed by a single operator ( E.K. ) . The evaluation was performed at least 1 year after surgery . For statistical analysis of the predisposing factors , the chi-square test and logistic regression were performed . RESULTS Of the 584 cases treated , 431 cases came for recall after a period of at least 12 months . Sex ( female ) , tooth position ( anterior ) , arch type ( maxilla ) , and lesion type ( isolated endodontic lesion ) were found to have a positive effect on surgical outcome . With regards to isolated endodontic lesions , the tooth position ( anterior ) , arch type ( maxilla ) , and type of restoration ( single/splinted crown , short bridge , and removable partial denture abutment ) were found to be pure positive predictors . CONCLUSIONS In endodontic microsurgery , it is likely that preoperative factors , particularly the tooth position and arch type , have a greater influence on the healing outcome than intra- and post-operative factors", "The two objectives of the present study were : to assess the healing after periradicular surgery using the Periotest device , and to compare the recorded Periotest values with the healing category determined after a one-year follow-up using radiographic and clinical criteria . In 43 patients with periradicular surgery , Periotest values could be recorded pre- and postoperatively , as well as after six and twelve months . Cases with a successful healing , as determined at the one-year follow-up , demonstrated a continuous decrease of the Periotest values over time , whereas one-year failures showed increasing Periotest values over the study period . In control teeth , the Periotest values remained unchanged for the whole study period . It appears that the Periotest measurements correlate with the postoperative healing mode following periradicular surgery , and therefore , allow an additional assessment of the healing outcome", "OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review", "This clinical study prospect ively evaluated the influence of various predictors on healing outcome 1 year after periapical surgery . The study cohort included 194 teeth in an equal number of patients . Three teeth were lost for the follow-up ( 1.5 % drop-out rate ) . Clinical and radiographic measures were used to determine the healing outcome . For statistical analysis , results were dichotomized ( healed versus nonhealed ) . The overall success rate was 83.8 % ( healed cases ) . The only individual predictors to prove significant for the outcome were pain at initial examination ( p=0.030 ) and other clinical signs or symptoms at initial examination ( p=0.042 ) , meaning that such teeth had lower healing rates 1 year after periapical surgery compared with teeth without such signs or symptoms . Logistic regression revealed that pain at initial examination ( odds ratio=2.59 , confidence interval=1.2 - 5.6 , p=0.04 ) was the only predictor reaching significance . Several predictors almost reached statistical significance : lesion size ( p=0.06 ) , retrofilling material ( p=0.06 ) , and postoperative healing course ( p=0.06 )", "This prospect i ve clinical study aim ed to evaluate the benefits of the endoscope as an aid to root-end management , and to assess the treatment outcome during 2 years following surgery . Forty-three endodontic surgical procedures in 30 patients were performed with the aid of an endoscope and followed for a period of 2 years . Radiographic criteria and clinical evaluation were used to assess the outcome . All cases were evaluated in terms of healing and functionality . 91.1 % and 90.7 % of the teeth evaluated after 1 and 2 years , respectively , were classified as successful . We found no statistically significant differences for both healing and functionality between the 1- and 2-year evaluations . No difference related to tooth type or tooth location was found at the 2-year follow-up . Fisher 's exact test was used to statistically assess the difference between successful and unsuccessful cases for each of the variables considered . The endoscope can be an aid for endodontic surgical procedures in terms of both periapical healing and functionality up to 2 years follow-up", "INTRODUCTION The long-term outcome of apical surgery performed on root-filled teeth presenting with post-treatment apical periodontitis has been the subject of debate ; therefore , current evidence is required to support the prognosis of this important procedure . The objectives of this study were ( 1 ) to assess the long-term outcome of apical surgery and ( 2 ) to identify significant outcome predictors in Phases 3 - 5 of the Toronto Study , pooled with the previously reported Phases 1 and 2 . METHODS The 4- to 10-year outcome of apical surgery was prospect ively assessed by a blinded , independent , calibrated examiner and dichotomized as \" healed \" ( periapical index score 261 treated teeth in the pooled sample , 96 were lost to follow-up , and 31 were extracted . Of the remaining 134 teeth ( 85 % recall , excluding 66 teeth that could not be recalled ) examined for outcome , 99 teeth ( 74 % ) were healed , and 126 teeth ( 94 % ) were functional . Three significant ( P age ( odds ratio [ OR ] , 2.5 ; confidence interval [ CI ] , 1.01 - 6.00 ; healed : > 45 years , 84 % , preoperative root-filling length ( OR , 3.4 ; CI , 1.34 - 8.76 ; healed : inadequate , 84 % ; adequate , 68 % ) , and size of the surgical crypt ( OR , 1.9 ; CI , 1.19 - 3.16 ; healed : 10 mm , 53 % ) . CONCLUSIONS In this 4- to 10-year cohort study , the outcome was better in subjects > 45 years old , teeth with inadequate root-filling length , and crypt size of < or=10 mm", "We did apicectomies of 30 teeth with periradicular lesions in 23 patients , using a 3 mm endoscope . Two patients failed to attend for postoperative assessment and of the remaining 21 patients who had 28 teeth treated the operation was judged after 1 year to be a success in 26 ( 93 % )", "INTRODUCTION The purpose of the present study was to evaluate the clinical outcomes of endodontic microsurgery when super ethoxy-benzoic acid ( Super EBA ; Harry J. Bosworth , Skokie , IL ) and mineral trioxide aggregate ( MTA ) were used as root-end filling material s in a prospect i ve r and omized controlled study . METHODS Of the 388 teeth eligible for endodontic microsurgery , 128 teeth were excluded from the study , and 260 teeth were r and omly assigned to either the Super EBA group or the MTA group with equal numbers using the \" minimization method . \" Endodontic microsurgical procedures were performed according to the Yonsei protocol reported in a previous study and were carried out by a single operator . The patients were followed up at 3 , 6 , and 12 months . The primary outcome measure was the change in the apical bone density at 12 months , and the secondary outcome measures were the presence of clinical symptoms or abnormal findings at 12 months . RESULTS A total of 192 teeth were examined at the 12-month follow-up ; 102 teeth were in the Super EBA group , and 90 were in the MTA group . The overall success rate was 94.3 % , with a success rate of 95.6 % ( 86/90 teeth ) for MTA and 93.1 % ( 95/102 teeth ) for Super EBA . The statistical analysis of the success rate results did not show any significant difference between the groups ( P = .472 ) . CONCLUSIONS In this prospect i ve r and omized controlled study , there was no significant difference in the clinical outcomes of endodontic microsurgery when Super EBA and MTA were used as root-end filling material", "Objective : To evaluate the clinical efficacy of polycarboxylate cement as retro grade filling material . Design : A prospect i ve clinical study was made of 25 patients subjected to periapical surgery with ultrasound and magnifying loupes , in which polycarboxylate cement was used as retro grade filling material . Measurements were made of the area and diameter of the lesions pre- and postoperatively , and 6 and 12 months after the operation . The apical resection and retro grade filling areas were also measured , and the prognosis following surgery was recorded . Results : A total of 23 patients with 31 apicoectomized teeth were studied ( 2 patients being lost to follow-up ) . The mean area of the periapical lesions before surgery was 52.25 mm2 , with a mean major diameter of 6.1 mm and a mean lesser diameter of 4.8 mm . The success rate after 12 months was 54.7 % , according to the criteria of Von Arx and Kurt . The prognosis was poorer in females , in larger lesions , and in cases with larger retro grade filling areas . Conclusions : Polycarboxylate cement offers good results , with important bone regeneration after periapical surgery . Key words : Periapical surgery , endodontic treatment , polycarboxylate cement", "AIM To assess the success rate of the root-end filling material , Mineral Trioxide Aggregate ( MTA ) . METHODOLOGY Referred adult patients were recruited using strict entry criteria and r and omly allocated to receive MTA or IRM . A st and ardized surgical technique was employed : the root end was resected perpendicularly and a root-end cavity was prepared ultrasonically and filled . A radiograph taken immediately after surgery was compared with those taken at 12 and 24 months . Customised film holders and the paralleling technique were used ; radiographs were assessed by two trained observers using agreed criteria . The results from 122 patients ( 58 in IRM group , 64 in MTA group ) after 12 months and 108 patients ( 47 in IRM group , 61 in MTA group ) for the 24-month review period were analysed using the chi2 test . RESULTS The highest number of teeth with complete healing at both times was observed when MTA was used . When the numbers of teeth with complete and incomplete ( scar ) healing , and those with uncertain and unsatisfactory healing were combined , the success rate for MTA was higher ( 84 % after 12 months , 92 % after 24 months ) compared with IRM ( 76 % after 12 months , 87 % after 24 months ) . However , statistical analysis showed no significant difference in success between material s ( P > 0.05 ) at both 12 and 24 months . CONCLUSIONS In this study , the use of MTA as a root-end filling material result ed in a high success rate that was not significantly better than that obtained using IRM", "AIM To evaluate treatment outcome after using a resin composite ( Retroplast , RP ) in combination with a dentine-bonding agent ( GLUMA ) as root-end filling material after 1 year as well as after more than 5 years ( final examination ) . Also , the influence of various pre- , intra- and postoperative factors on the treatment outcome was studied . METHODOLOGY All patients ( 87 ) undergoing root-end resection consecutively treated by root-end filling with RP on an incisor , canine , pre-molar , or first molar ( 87 teeth , 118 roots ) were initially enrolled in the study . RP was applied on the entire resected surface that was prepared to a slightly concave shape and after conditioning with EDTA and GLUMA . The treatment outcome involving subjective , clinical and radiographic parameters was evaluated after 1 year and at the final examination . A total of 27 patients ( 36 roots ) were excluded from the study because of unavailability of follow-up ( 19 ) and extraction of the operated tooth for reasons other than failed surgery ( 8) . Consequently , 60 patients ( 82 roots ) were included in the final material . The mean follow-up period at the final examination was 8 years ( range : 6.5 - 9 years ) . RESULTS The radiographic evaluation at the final examination revealed that 77 % , 5 % , 7 % and 11 % of the treated roots were characterized by complete , incomplete , uncertain and unsatisfactory healing , respectively . A total of 95 % of the roots classified as completely healed at the 1-year control were also completely healed at the final examination . Two roots ( 5 % ) showing complete healing at the 1-year control revealed unsatisfactory healing at the final examination because of displaced or lost RP-filling . Moreover , 60 % of the roots with uncertain healing at the 1-year control demonstrated complete or incomplete healing at the final examination . The classification according to subjective , clinical and radiographic parameters revealed that 78 % of the teeth were characterized by a successful treatment outcome at the final examination . Evaluation of the influence of various pre- , intra- and postoperative factors on the treatment outcome revealed that the radiographic classification at the final examination was exclusively influenced by the radiographic classification at the 1-year control ( P RP can be used for root-end filling with a successful treatment outcome ", "Apical endodontic surgery is applied frequently following a failed conventional endodontic treatment . The apical preparation can be carried out conventionally using a round bur or using an endodontic ultrasonic system . The purpose of this study was to compare the outcome of the 2 treatment options by a r and omized prospect i ve clinical study . Patients ( n=399 ) were at r and om allocated to treatment using a conventional round bur or using an ultrasonic system ( P-max Newtron ) according to a for the rest similar treatment protocol . One year post treatment , the treatment outcomes were determined by 2 oral and maxillofacial surgeons , blinded for the treatment option . Adequate follow-up data were obtained from 290 patients . The overall success rate was 71 % in the patients treated conventionally and 81 % in the patients treated using the ultrasonic system . In molar teeth , the difference in success rate was statistically significant", "OBJECTIVE The purpose of this prospect i ve clinical study was to monitor the outcome of ultrasonic root-end preparation , in relation to tooth type and location , presence of post restoration and type of retrotip . STUDY DESIGN Teeth treated surgically showed a periradicular lesion of strictly endodontic origin . Fifty teeth were included in the study , according to specific selection criteria . Cases were followed for a period of 1 year and then classified in 3 groups ( success , uncertain healing , and failure ) according to radiographic and clinical criteria . RESULTS Of the 46 teeth evaluated at 1-year follow-up , 42 teeth ( 91.3 % ) successfully healed , 1 tooth had uncertain healing , and 3 failed . We found no statistically significant differences in treatment results related to the type of tooth , tooth location , post restoration , and type of retrotip . CONCLUSION Adherence to a strict endodontic surgical protocol and the use of contemporary techniques and material s can lead to a predictable outcome", "PURPOSE The introduction of microsurgical instruments and magnification devices has brought advantages in root-end management and the application of root-end filling material s. The main purpose of this prospect i ve clinical study was to monitor the outcome of ultrasonic root-end preparation using magnification loupes or an endoscope . Tooth location and the presence of post restoration were also examined as potentially affecting the outcome . MATERIAL S AND METHODS Teeth treated surgically showed a periradicular lesion of strictly endodontic origin . A total of 59 patients were included in the study , according to specific selection criteria . Following the reflection of a full mucoperiosteal tissue flap , residual soft tissues were curetted , root ends were resected , and root-end cavities were prepared ultrasonically with a zirconium nitrate tip , and zinc oxide EBA-reinforced cement root-end fillings were placed . Thirty-two root-end management procedures were performed using magnification loupes and 39 using an endoscope . All cases followed for a period of 1 year were classified into 3 groups ( success , uncertain healing , and failure ) according to radiographic and clinical criteria . RESULTS Of the 71 teeth evaluated at 1-year follow-up , 67 teeth ( 92.95 % ) successfully healed , 3 teeth had uncertain healing , and 2 failed . In the group using endoscopy , 94.9 % of successful healing was achieved , while for the other group , 90.6 % was recorded . We found no statistically significant differences in treatment results related to the arch ( P = .20 ) , post restoration ( P = .21 ) , or type of magnification device ( P = .08 ) . CONCLUSIONS In the present study , adherence to a strict endodontic surgical protocol and the use of modern surgical endodontic procedures , together with visual magnifications , result ed in an overall high success rate", "A total of 129 teeth with periradicular surgeries ( apicoectomies ) were analyzed in a prospect i ve clinical study . In the test group including 62 teeth , an endoscope ( Tele-Otoscope with a 70 degrees viewing angle ) was used as an intraoperative visualization aid to monitor the following surgical steps : root-end resection , root-end cavity preparation and retro grade root-canal obturation . In the control group including 67 teeth , intraoperative diagnostics were carried out using micromirrors . Fifty-four and 61 teeth could be re-examined after one year . Based on the clinical and radiographic findings they were categorized as success , uncertain healing or failure . In the test group with endoscopy , the success rate was 88.9 % , whereas in the control group it was only 75.4 % . However , statistically no significant difference was found between the two groups . Additional experimental and clinical studies will show if endoscopy will improve the success rates in periradicular surgery any further", "AIM To compare healing after root-end resection with a root-end filling of mineral trioxide aggregate ( MTA ) or smoothing of the ortho grade gutta-percha ( GP ) root filling . METHODOLOGY Forty-four patients ( consisting of 52 teeth with periapical infection ) , average age of 54.6 years ( range 30 - 77 ) participated in a r and omized clinical trial ( RCT ) comparing the MTA and GP treatment methods . Radiographs produced 1-week and 12 months post-operatively were compared after blinding for treatment method , and healing was assessed as complete , incomplete , uncertain , or unsatisfactory . RESULTS Six teeth were not available for the 12-month follow-up : three teeth ( GP ) had been re-operated because of pain and two teeth ( one GP , one MTA ) had been extracted because of root fracture ( these five teeth were classified as failures ) . One patient ( GP ) was not available for recall . In the GP group , seven teeth ( 28 % ) showed complete healing , six teeth ( 24 % ) incomplete healing , six teeth ( 24 % ) uncertain healing and two teeth ( 8 % ) unsatisfactory healing after 1 year . In the MTA group , 22 teeth ( 85 % ) showed complete healing , three teeth ( 12 % ) incomplete healing , and none were scored as uncertain or unsatisfactory healing after 1 year . The difference in healing between the GP and the MTA groups was significant ( P MTA had significantly better healing ( 96 % ) than teeth treated by smoothing of the ortho grade GP root filling only ( 52 % )", "OBJECTIVE The aim of this study was to evaluate the healing outcome after periapical surgery with an ultrasonic cleaning technique in conjunction with the use of either of 2 different retro grade root-filling material s in teeth with apical periodontitis . STUDY DESIGN One hundred sixty teeth in 139 consecutive patients were r and omly allocated into 2 groups receiving either IRM or thermoplasticized gutta-percha ( GP ) with AH Plus sealer as a retro grade root-end seal . The patients were review ed 12 months after surgery . The results were analyzed with Fisher exact test . RESULTS One hundred forty-seven teeth in 131 patients were review ed . Radiologic evaluation and clinical examination showed an 85 % success rate for the IRM group and 90 % for GP group . There was no statistical significance between the 2 groups . CONCLUSION Both tested material s , IRM and GP , are suitable as retro grade root-end filling material s in conjunction with ultrasonic root-end preparation according to the results of the healing outcome after 12 months follow-up", "PURPOSE The aim of the present prospect i ve , r and omized , controlled , clinical study was to compare the outcomes of periradicular surgery of the maxillary first molar tooth using the vestibular approach between 2 preoperative radiologic evaluation methods : cone beam computed tomography ( CBCT ) and conventional radiography . PATIENTS AND METHODS Periradicular surgery was applied to the maxillary first molar tooth in 40 patients . The patients were divided into 2 groups . The patients in group 1 underwent examination and preoperative planning with CBCT , and the patients in group 2 underwent examination and preoperative planning with conventional radiography . The outcomes of the treatment were evaluated radiographically and clinical ly , and the data were analyzed statistically . RESULTS The mean operative time was significantly shorter in group 1 than in group 2 . According to the radiographic and clinical healing criteria used in the present study , the healing of patients in group 1 was rated as a success in 35 % , an improvement in 40 % , and a failure in 25 % . In the group 2 patients , healing was rated as a success in 42.1 % , an improvement in 31.6 % , and a failure in 26.3 % . Sinus membrane elevation was performed in 92.3 % of all patients . Sinus membrane perforation occurred in 20 % of the patients in group 1 and 36.8 % of the patients in group 2 . CONCLUSIONS Periradicular surgery of maxillary first molars using a vestibular approach is a viable treatment method with a low complication rate . Preoperative CBCT examination demonstrated positive contributions to the treatment outcomes", "OBJECTIVE To evaluate the effect of patient- and tooth-related factors on the outcome of apical surgery in a multicenter study . METHOD AND MATERIAL S A total of 281 teeth in 255 patients undergoing periradicular surgery were investigated clinical ly and radiographically 6 to 12 months postoperatively . RESULTS The overall success rate was 88.0 % . Sex was a significant ( P = .024 ) predictor , with a success rate of 89.8 % in females and 84.0 % in males . The success rate was significantly higher in patients 31 to 40 years of age . The treatment of premolars result ed in a significantly higher success rate ( 91.9 % ) than the treatment of anterior teeth ( 86.1 % , P = .042 ) and molars ( 86.4 % , P = .026 ) . The loss of the buccal bone plate and the extension of apical osteolysis to the furcation area in molars result ed in a considerably lower success rate . Lesion size , preoperative pain , tenderness to percussion , fistula , and resurgery were significant factors . CONCLUSION There are several factors influencing the success rate of apical surgery that must be taken into account when considering apical surgery as a treatment alternative", "Abstract Objective . To compare the clinical and radiographic treatment outcome of retro grade root filling with either dentin-bonded resin composite ( Retroplast , RP ) or glass ionomer cement ( Chelon-Silver , CS ) . Study design . A prospect i ve , r and omized clinical study of 134 consecutive patients with indication of retro grade root filling of an incisor , canine , premolar , or first molar . Either RP or CS was chosen at r and om as retro grade filling material . Either material was applied onto the entire resection surface after prepared slightly concave . This preparation technique makes a sealing of the entire resection surface possible and prevents marginal contraction gaps during polymerization . A total of 122 patients were available for 1-year follow-up . Results . After 1 year the proportion of successful cases was significantly higher in the RP group ( 73 % ) than in the CS group ( 31 % ) ( p Doubtful healing with a need for a longer observation period was seen in 17 % of the RP cases and 19 % of the CS cases . The proportion of failures in the RP group ( 10 % ) was significantly lower than that in the CS group ( 50 % ) ( p CS cases failed due to loosening of the retro grade filling . Conclusions . Dentin-bonded RP applied onto the entire , slightly concave resection surface is a predictable apical sealant characterized by a high success rate . In contrast , retro grade root filling with CS results in an unacceptably high failure rate due to insufficient bonding strength to the concave resection surface", "Using an endoscope in periradicular surgery provides an impressive optical enlargement and may lead to better clinical diagnostics and a high rate of success . Aims of this investigation were examining this hypothesis as well as detecting influencing factors . In 2002 and 2003 , 114 teeth of 91 patients were root-end resected using endoscope . Before surgery , the tooth , number of resected root-ends , content of root channels , clinical diagnosis and moment of surgery were recorded . Patients were controlled one year after surgery and success was evaluated as a summary of clinical and radiological findings . Four patients did not reappear for the control examination . Out of 110 teeth , treatment was successful in 91.8 % and failed in 7.3 % . 0.9 % could not be classified . Statistically , more failures were noted after periradicular surgery in molars . The rate of success increased during the study by means of a learning curve . The results confirm the hypothesis that where using an endoscope periradicular surgery is highly successful", "INTRODUCTION The aim of the study was to compare the healing responses of platelet-rich plasma ( PRP ) , PRP + a collagen sponge , and a collagen membrane used as guided tissue regeneration ( GTR ) material s for the treatment of apicomarginal defects . METHODS Thirty patients with suppurative chronic apical periodontitis and apicomarginal communication were selected and allocated r and omly into three groups according to the barrier technique to be used during periradicular surgery : the collagen membrane group , the PRP group , and the PRP + collagen sponge group . Clinical and radiographic measurements were determined at baseline and every 3 months after surgery up to 1 year . Cases were defined as healed when no clinical signs or symptoms were present , and radiographs showed complete or incomplete ( scar tissue ) healing of previous radiolucencies . RESULTS The PRP and PRP + collagen sponge groups depicted 83.33 % and 88.89 % healing , respectively , in terms of combined clinical -radiographic healing as compared with 80 % in the collagen membrane group . All the three treatments showed highly significant ( P periodontal pocket depth ( PD ) , the clinical attachment level ( CAL ) , the gingival margin position ( GMP ) , the size of the periapical lesion , the percentage reduction of the periapical rarefactions , and periapical healing . No significant differences between the three groups were evident for these parameters ( P > .05 ) . CONCLUSIONS GTR applied to apicomarginal defects using PRP or PRP + collagen sponge lead to similar enhancements of the clinical outcome of periradicular surgery in terms of periapical healing , gain of periodontal support , PD reduction , and PRP may be an alternative treatment for GTR membrane in the treatment of apicomarginal defects", "INTRODUCTION The purpose of the present study was to evaluate the long-term clinical outcome of endodontic microsurgery when mineral trioxide aggregate ( MTA ) and super ethoxybenzoic acid ( Super EBA ; Harry J. Bosworth , Skokie , IL ) were used as root-end filling material s. Additionally , this study aim ed to compare the clinical outcome of endodontic microsurgery at the 1-year follow-up with that at the 4-year follow-up . METHODS Two hundred sixty teeth were r and omly assigned to either the MTA or Super EBA group in equal numbers using the minimization method . Endodontic microsurgery was performed according to the Yonsei protocol . The previous study of 192 teeth examined at the 1-year follow-up revealed a success rate of 95.6 % for MTA and 93.1 % for Super EBA . Patients were recalled 4 years after surgery , and treated teeth were classified as successes or failures with Molven 's criteria . The Pearson chi-square test and the McNemar test were conducted to analyze and compare the success rates . RESULTS A total of 182 teeth were examined at the 4-year follow-up . The success rate was 91.6 % for MTA and 89.9 % for Super EBA . Statistical analysis of the success rate did not show any significant difference between the 2 material s ( P = .8 ) . The overall success rate at the 4-year follow-up was 89.5 % , which was slightly lower compared with 94.3 % at the 1-year follow-up . However , there was no significant difference between the follow-up periods ( P = .063 ) . CONCLUSIONS This study identified no significant difference in the 4-year success rates of MTA and Super EBA as root-end filling material s in endodontic microsurgery . Additionally , compared with short-term outcomes , long-term follow-up outcomes were not significantly different", "OBJECTIVE This study evaluated the treatment outcome after periapical surgery with the use of 2 different retro grade root-filling material s and the influence of 3 pre- and perioperative variables on the periapical healing . STUDY DESIGN Two hundred six teeth in 164 patients were r and omly allocated to receive either IRM or Super-EBA as a retro grade root-end seal . The teeth were review ed 12 months after surgery . The influence of lesion size , lesion type , and ortho grade root filling quality on healing was analyzed . RESULTS One hundred ninety-four teeth in 153 patients were review ed . Radiologic evaluation and clinical examination revealed 91 % success rate for the IRM group and 82 % for the Super-EBA group . There was no statistical significance in the healing outcome between the 2 groups ( Fisher exact test ) . The analyzed pre- and perioperative variables had no significant influence on the treatment outcome ( Z test ) . CONCLUSIONS Both retro grade material s tested in this study can serve as a root-end seal in periapical infected teeth , according to the results of the healing outcome after 12 months ' follow-up", "INTRODUCTION The purpose of this prospect i ve , r and omized controlled trial was to evaluate the healing outcomes of platelet-rich fibrin ( PRF ) in periapical surgeries involving apicomarginal defects and to compare these results with surgeries not using any guided tissue regeneration techniques . METHODS Thirty patients with suppurative chronic apical periodontitis and apicomarginal communication were r and omly assigned to either the PRF or the control group . Clinical and radiographic parameters including pocket depth ( PD ) , clinical attachment level , gingival marginal position , size of periapical lesion , and percentage reduction of the periapical radiolucency were recorded at baseline and at an interval of 3 months for a period of 12 months . RESULTS The overall success rate was 83.33 % , with a success rate of 86.66 % ( 13 of 15 teeth ) for PRF group and 80 % ( 12 of 15 teeth ) for control group . Both the groups exhibited a significant reduction in PD , clinical attachment level , gingival marginal position , and size of periapical lesion at 12-month period . No significant differences were observed between the 2 groups for these parameters except PD , which showed a statistically significant reduction in the PRF group ( P regenerative techniques may not promote healing of apicomarginal defects of endodontic origin", "OBJECTIVE This study investigates the treatment outcome of a root-end filling technique that uses a light-cured compomer combined with a light-cured dental adhesive . STUDY DESIGN The study used 34 single-rooted teeth restored with post , core , and crowns . A shallow concave apical preparation was filled with a light-cured compomer with a light-cured dental adhesive . As a control , a chemically cured glass ionomer was used with a conventional root-end preparation . A follow-up clinical and radiographic evaluation of the treatment result was conducted after 1 year . RESULTS A significantly higher success rate ( P compomer ( 89 % complete healing ) compared to glass ionomer ( 44 % complete healing ) . CONCLUSIONS When used as a retro grade root filling in a shallow concave preparation , a light-cured compomer and a dental adhesive improves healing regardless of the quality of the remaining root filling", "A retro grade root-end cover with a special resin composite ( Retroplast ) combined with the dentin bonding agent Gluma ( Bayer AG ) has been used since 1984 by the authors . Its content of silver , added to promote radiopacity , has been found to lower the working time and storage stability of the composite and might cause discolorations . Since 1990 , silver has therefore been replaced with ytterbium trifluoride , which eliminates these side effects . The purpose of this study was to compare the clinical results obtained with these two resin composites and to evaluate the healing results after several years in function . Apical fillings ( 351 ) with the modified Retroplast showed the following radiographic healing pattern 1 yr after surgery : 80 % complete healing , 2 % scar tissue , 12 % uncertain healing , and 6 % failure . No significant difference in this healing pattern was found , compared with that obtained with the silver-containing Retroplast . Cases with ytterbium trifluoride classified as scar tissue and uncertain healing at 1 yr when examined at 2 to 4 yr postoperatively showed 89 % complete healing . 0 % scar tissue , 1 % uncertain healing , and 9 % failure . This result is significantly different from that obtained 1 yr after surgery . Based on calculations , it was predicted that with time 90 % will become complete healing , whereas 10 % will become failure", "INTRODUCTION The aim of apical surgery is to hermetically seal the root canal system after root-end resection , thereby enabling periradicular healing . The objective of this nonr and omized prospect i ve clinical study was to report results of 2 different root-end preparation and filling methods , ie , mineral trioxide aggregate ( MTA ) and an adhesive resin composite ( Retroplast ) . METHODS The study included 353 consecutive cases with endodontic lesions limited to the periapical area . Root-end cavities were prepared with sonic microtips and filled with MTA ( n = 178 ) , or alternatively , a shallow concavity was prepared in the cut root face , with subsequent placement of an adhesive resin composite ( Retroplast ) ( n = 175 ) . Patients were recalled after 1 year . Cases were defined as healed when no clinical signs or symptoms were present and radiographs demonstrated complete or incomplete ( scar tissue ) healing of previous radiolucencies . RESULTS The overall rate of healed cases was 85.5 % . MTA-treated teeth demonstrated a significantly ( P = .003 ) higher rate of healed cases ( 91.3 % ) compared with Retroplast-treated teeth ( 79.5 % ) . Within the MTA group , 89.5%-100 % of cases were classified as healed , depending on the type of treated tooth . In contrast , more variable rates ranging from 66.7%-100 % were found in the Retroplast group . In particular , m and ibular premolars and molars demonstrated considerably lower rates of healed cases when treated with Retroplast . CONCLUSIONS MTA can be recommended for root-end filling in apical surgery , irrespective of the type of treated tooth . Retroplast should be used with caution for root-end sealing in apical surgery of m and ibular premolars and molars", "This clinical study prospect ively evaluated the healing outcome 1 year after apical surgery in relation to bony crypt dimensions measured intraoperatively . The study cohort included 183 teeth in an equal number of patients . For statistical analysis , results were dichotomized ( healed versus non-healed cases ) . The overall success rate was 83 % ( healed cases ) . Healing outcome was not significantly related to the level and height of the facial bone plate . In contrast , a significant difference was found for the mean size of the bony crypt when healed cases ( 395 mm(3 ) ) were compared with non-healed cases ( 554 mm(3 ) ) . In addition , healed cases had a significantly shorter mean distance ( 4.30 mm ) from the facial bone surface to the root canal ( horizontal access ) compared with non-healed cases ( 5.13 mm ) . With logistic regression , however , the only parameter found to be significantly related to healing outcome was the length of the access window to the bony crypt", "For a prospect i ve r and omized clinical trial with two groups , the relative risk can be used as a measure of treatment effect and is directly interpretable as the ratio of success probabilities in the new treatment group versus the placebo group . For a prospect i ve study with many covariates and a binary outcome ( success or failure ) , relative risk regression may be of interest . If we model the log of the success probability as a linear function of covariates , the regression coefficients are log-relative risks . However , using such a log-linear model with a Bernoulli likelihood can lead to convergence problems in the Newton-Raphson algorithm . This is likely to occur when the success probabilities are close to one . A constrained likelihood method proposed by Wacholder ( 1986 , American Journal of Epidemiology 123 , 174 - 184 ) , also has convergence problems . We propose a quasi-likelihood method of moments technique in which we naively assume the Bernoulli outcome is Poisson , with the mean ( success probability ) following a log-linear model . We use the Poisson maximum likelihood equations to estimate the regression coefficients without constraints . Using method of moment ideas , one can show that the estimates using the Poisson likelihood will be consistent and asymptotically normal . We apply these methods to a double-blinded r and omized trial in primary biliary cirrhosis of the liver ( Markus et al. , 1989 , New Engl and Journal of Medicine 320 , 1709 - 1713 )", "The purpose of this prospect i ve , r and omized , clinical study was to monitor the outcome of periradicular surgery , in which either a surgical microscope or an endoscope was used as a magnification device . A total of 113 teeth in 70 patients were included in the study , according to specific selection criteria . The choice of endoscope or surgical microscope was made using a r and omized table . One hundred cases were followed for at least 2 years . Of these , 59 root-end management procedures were performed using a microscope and 41 using an endoscope . At the 2-year follow-up they were classified into three groups ( success , uncertain healing and failure ) according to radiographic and clinical criteria . After a 2-year follow-up , 91 teeth ( 91 % ) healed successfully . In the group using an endoscope 90 % of successful healing was achieved , while 92 % of success was recorded for the group using a microscope . No statistically significant difference was found in the treatment results relating to the type of magnification device . The type of magnification device used did not seem to affect the outcome of endodontic surgery", "INTRODUCTION The purpose of this prospect i ve clinical study was to evaluate the clinical outcome of endodontic microsurgery on roots exhibiting the presence or absence of dentinal defects at 1-year and 3-year follow-up period . METHODS One hundred fifty-five teeth were treated with periapical microsurgery using a modern microsurgical protocol in a private practice setting . The root apices were resected and inspected for dentinal defects with a surgical operating microscope and a 0.8-mm head diameter light-emitting diode microscope diagnostic probe light . After inspection , root-end preparations were performed using ultrasonic tips , and root-end fillings were placed . Follow-up visits occurred at 1 year and 3 years postoperatively . The primary outcome measure used was the change in the radiographic apical bone density , and the secondary outcome measure used was the absence of clinical symptoms . RESULTS Of the 155 treated teeth , a total of 134 teeth were assessed at the 1-year follow-up and 127 teeth at the 3-year evaluation . In the \" intact \" group , 94.8 % healed at 1 year , and 97.3 % healed at 3 years . In the \" dentinal defect \" group , 29.8 % healed at 1 year , and 31.5 % healed at 3 years . The baseline root condition of either \" dentinal defect \" or \" intact \" showed a statistical difference in the healing outcome at both 1 and 3 years . CONCLUSIONS This prospect i ve periapical microsurgery study showed a significant superior clinical outcome for intact roots when compared with roots with dentinal defects at both 1 year and at 3 years postoperatively" ]

[ "Walnuts are rich in polyunsaturated fatty acids and have been shown to improve various cardiometabolic risk factors . We aim ed to investigate the association between walnut intake and incident type 2 diabetes in 2 large cohort studies : the Nurses ’ Health Study ( NHS ) and NHS II . We prospect ively followed 58,063 women aged 52–77 y in NHS ( 1998–2008 ) and 79,893 women aged 35–52 y in NHS II ( 1999–2009 ) without diabetes , cardiovascular disease , or cancer at baseline . Consumption of walnuts and other nuts was assessed every 4 y using vali date d food frequency question naires . Self-reported type 2 diabetes was confirmed by a vali date d supplemental question naire . We documented a total of 5930 incident type 2 diabetes cases during 10 y of follow-up . In the multivariable-adjusted Cox proportional hazards model without body mass index ( BMI ) , walnut consumption was associated with a lower risk of type 2 diabetes , and the HRs ( 95 % CIs ) for participants consuming 1–3 servings/mo ( 1 serving = 28 g ) , 1 serving/wk , and ≥2 servings/wk of walnuts were 0.93 ( 0.88–0.99 ) , 0.81 ( 0.70–0.94 ) , and 0.67 ( 0.54–0.82 ) compared with women who never/rarely consumed walnuts ( P-trend consumption of total nuts ( P-trend and other tree nuts ( P-trend = 0.03 ) was also inversely associated with risk of type 2 diabetes , and the associations were largely explained by BMI . Our results suggest that higher walnut consumption is associated with a significantly lower risk of type 2 diabetes in women", "BACKGROUND The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus ( DM2 ) is unclear . Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates . AIM The effects of a low carbohydrate Mediterranean ( LCM ) , a traditional Mediterranean ( TM ) , and the 2003 American Diabetic Association ( ADA ) diet were compared , on health parameters during a 12-month period . METHODS In this 12-month trial , 259 overweight diabetic patients ( mean age 55 years , mean body mass index 31.4 kg/m(2 ) ) were r and omly assigned to one of the three diets . The primary end-points were reduction of fasting plasma glucose , HbA1c and triglyceride ( TG ) levels . RESULTS 194 patients out of 259 ( 74.9 % ) completed follow-up . After 12 months , the mean weight loss for all patients was 8.3 kg : 7.7 kg for ADA , 7.4 kg for TM and 10.1 kg for LCM diets . The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet ( -2.0 and -1.6 % , respectively , p HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p reduction in serum TG was greater in the LCM ( -1.3 mmol/l ) and TM ( -1.5 mmol/l ) than in the ADA ( -0.7 mmol/l ) , p = 0.001 . CONCLUSIONS An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups . Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control", "Saturated fatty acids ( SFA ) and monounsaturated fatty acids ( MUFA ) show different effects on the development of insulin resistance . In this study , we compared the effect of dietary SFA and MUFA on the insulin signaling pathway in the skeletal muscle of a type 2 diabetic animal model . Twenty-nine-week-old male Otsuka Long-Evans Tokushima fatty ( OLETF ) rats were r and omly divided into three groups and fed one of the following diets for 3 weeks ; a normal chow diet , an SFA ( lard oil ) enriched or a MUFA ( olive oil ) enriched high-fat diet . The vastus lateralis muscle was used for analyses . Insulin tolerance test showed improved insulin sensitivity in rats fed the MUFA diet , as compared to those fed the SFA diet ( p reduced IRS-1 expression and phosphorylated PI3 K levels in skeletal muscle , as compared with a chow diet ( p muscle IRS-2 expression and phosphorylated ERK1/2 was significantly increased in rats fed the SFA diet ( p Membrane translocation of glucose transporter type 4 decreased in the skeletal muscle of rats fed the SFA diet , as compared to those fed a chow diet ( p insulin signaling pathway in skeletal muscle were not observed in rats fed the MUFA diet . In conclusion , the beneficial effect of dietary MUFA on insulin sensitivity is associated with a conserved IRS-1/PI3 K insulin signaling pathway which was altered by dietary SFA", "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", "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", "CONTEXT Nuts are high in unsaturated ( polyunsaturated and monounsaturated ) fat and other nutrients that may improve glucose and insulin homeostasis . OBJECTIVE To examine prospect ively the relationship between nut consumption and risk of type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 83 818 women from 11 states in the Nurses ' Health Study . The women were aged 34 to 59 years , had no history of diabetes , cardiovascular disease , or cancer , completed a vali date d dietary question naire at baseline in 1980 , and were followed up for 16 years . MAIN OUTCOME MEASURE Incident cases of type 2 diabetes . RESULTS We documented 3206 new cases of type 2 diabetes . Nut consumption was inversely associated with risk of type 2 diabetes after adjustment for age , body mass index ( BMI ) , family history of diabetes , physical activity , smoking , alcohol use , and total energy intake . The multivariate relative risks ( RRs ) across categories of nut consumption ( never/almost never , or = 5 times/week ) for a 28-g ( 1 oz ) serving size were 1.0 , 0.92 ( 95 % confidence interval [ CI ] , 0.85 - 1.00 ) , 0.84 ( 0.95 % CI , 0.76 - 0.93 ) , and 0.73 ( 95 % CI , 0.60 - 0.89 ) ( P for trend fats , cereal fiber , and other dietary factors did not appreciably change the results . The inverse association persisted within strata defined by levels of BMI , smoking , alcohol use , and other diabetes risk factors . Consumption of peanut butter was also inversely associated with type 2 diabetes . The multivariate RR was 0.79 ( 95 % CI , 0.68 - 0.91 ; P for trend peanut butter 5 times or more a week ( equivalent to > or = 140 g [ 5 oz ] of peanuts/week ) compared with those who never/almost never ate peanut butter . CONCLUSIONS Our findings suggest potential benefits of higher nut and peanut butter consumption in lowering risk of type 2 diabetes in women . To avoid increasing caloric intake , regular nut consumption can be recommended as a replacement for consumption of refined grain products or red or processed meats", "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 ", "Background / Objectives : Although benefits have been attributed to the Mediterranean diet , its effect on glycaemic control has not been totally eluci date d. The aim of this work was to compare the effect of two Mediterranean diets versus a low-fat diet on several parameters and indices related to glycaemic control in type 2 diabetic subjects . Subjects/ Methods : A multicentric parallel trial was conducted on 191 participants ( 77 men and 114 women ) of the PREDIMED study in order to compare three dietary interventions : two Mediterranean diets supplemented with virgin olive oil ( n=67 ; body mass index ( BMI ) = 29.4±2.9 ) or mixed nuts ( n=74 ; BMI = 30.1±3.1 ) and a low-fat diet ( n=50 ; BMI = 29.8±2.8 ) . There were no drop-outs . Changes in body weight and waist circumference were determined . Insulin resistance was measured by HOMA-IR index , adiponectin/leptin and adiponectin/HOMA-R ratios after 1 year of follow-up . Results : Increased values of adiponectin/leptin ratio ( P=0.043 , P=0.001 and P for low-fat , olive oil and nut diets , respectively ) and adiponectin/HOMA-IR ratio ( P=0.061 , P=0.027 and P=0.069 for low-fat , olive oil and nut diets , respectively ) and decreased values of waist circumference ( P=0.003 , P=0.001 and P=0.001 for low-fat , olive oil and nut diets , respectively ) were observed in the three groups . In both Mediterranean diet groups , but not in the low-fat diet group , this was associated with a significant reduction in body weight ( P=0.347 , P=0.003 and P=0.021 for low-fat , olive oil and nut diets , respectively ) . Conclusions : Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet", "BACKGROUND The rapid emergence of coronary artery disease ( CAD ) in south Asian people is not explained by conventional risk factors . In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid , we assessed the benefits of this diet for patients at high risk of CAD . METHODS We did a r and omised , single-blind trial in 1000 patients with angina pectoris , myocardial infa rct ion , or surrogate risk factors for CAD . 499 patients were allocated to a diet rich in whole grains , fruits , vegetables , walnuts , and almonds . 501 controls consumed a local diet similar to the step I National Cholesterol Education Program ( NCEP ) prudent diet . FINDINGS The intervention group consumed more fruits , vegetables , legumes , walnuts , and almonds than did controls ( 573 g [ SD 127 ] vs 231 g [ 19 ] per day p intake of whole grains and mustard or soy bean oil . The mean intake of alpha-linolenic acid was two-fold greater in the intervention group ( 1.8 g [ SD 0.4 ] vs 0.8 g [ 0.2 ] per day , p Total cardiac end points were significantly fewer in the intervention group than the controls ( 39 vs 76 events , p Sudden cardiac deaths were also reduced ( 6 vs 16 , p=0.015 ) , as were non-fatal myocardial infa rct ions ( 21 vs 43 , p serum cholesterol concentration and other risk factors in both groups , but especially in the intervention diet group . In the treatment group , patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group . INTERPRETATION An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet", "Context Mediterranean-style diets improve control of coronary risk factors and hyperglycemia , but few direct comparisons of the diet with other st and ard diets have been done . Contribution In this r and omized clinical trial , patients with newly diagnosed type 2 diabetes who were assigned to a low-carbohydrate , Mediterranean-style diet had better glycemic control and were less likely to need oral antihyperglycemic therapy than patients assigned to a low-fat diet . Caution The trial was unblinded , and dietary intake was self-reported . Implication A low-carbohydrate , Mediterranean-style diet seems to be preferable to a low-fat diet for glycemic control in patients with newly diagnosed type 2 diabetes . The Editors The p and emic of type 2 diabetes is an enormous public health problem , with 380 million cases worldwide projected by 2025 ( 1 , 2 ) . Lifestyle intervention studies ( 3 ) have demonstrated large reductions in risk for type 2 diabetes that remain after lifestyle counseling is stopped ( 4 , 5 ) . Despite this beneficial effect , the American Diabetes Association ( ADA ) recommends that patients with newly diagnosed type 2 diabetes be treated with pharmacotherapy as well as lifestyle changes ( 6 ) . The rationale for combination therapy is presumably that each form of treatment alone is imperfect . Lifestyle changes are often inadequate because patients do not lose weight or regain weight or their diabetes worsens independent of weight ( 6 ) . Pharmacotherapy also often fails with time ( 7 ) , and some drugs have associated cardiovascular and other risks ( 8 , 9 ) . For those reasons , lifestyle changes proven to be more effective than what is typically recommended would be welcome . For example , Mediterranean-style ( MED ) diets with a high proportion of monounsaturated fat provide cardiovascular benefits and increase insulin sensitivity ( 1012 ) , and the ADA recommends low-carbohydrate or low-fat , calorie-restricted diets for weight loss in overweight and obese patients with type 2 diabetes ( 13 ) . However , few direct , long-term comparisons of the 2 diets in patients with diabetes have been done ( 11 ) . We conducted a r and omized trial to compare the effectiveness , durability , and safety of a low-carbohydrate MED diet and a low-fat diet on glycemic control in patients with newly diagnosed type 2 diabetes . Methods We conducted the trial between January 2004 ( first patient enrolled ) and September 2008 ( end of follow-up of the last patient ) at the research center of the Diabetes Clinic of the Azienda Ospedaliera Universitaria , Second University of Naples , Naples , Italy , in accordance with the Declaration of Helsinki and with the institutional review board 's approval . Screening Phase We recruited men and women with newly diagnosed type 2 diabetes by ADA criteria who had never been treated with antihyperglycemic drugs from the clinical practice s of trial investigators and screened them for eligibility . Inclusion criteria were age 30 to 75 years , body mass index ( BMI ) greater than 25 kg/m2 , and hemoglobin A1c ( HbA1c ) level less than 11 % . Participants also had to be sedentary ( To minimize the likelihood of including participants with late-onset type 1 diabetes , we screened c and i date s by testing for antibodies to glutamate decarboxylase and measuring fasting plasma C-peptides . We excluded patients with positive antibodies or C-peptide levels less than 0.25 pmol/L ( We also excluded patients with abnormal laboratory test results , including liver enzyme levels ( alanine aminotransferase , aspartate aminotransferase , and alkaline phosphatase ) greater than 3 times the upper limit of normal and serum creatinine levels greater than 123.8 mol/L ( > 1.4 mg/dL ) . We required that participants successfully self-monitor their diet and physical activity over a 2-week run-in period . We provided dietary education during that time that emphasized the importance of eating a healthy diet and being physically active for both weight loss and improvement of glycemic control . Participants were also taught to prepare their own meals at home . We encouraged all individuals who smoked to quit and provided self-help material s , referral to local programs , or both , as appropriate . R and omization and Blinding After obtaining informed consent , we r and omly assigned patients to 1 of the 2 study diets by using a computer-generated r and om-number sequence ( simple r and omization ) . Allocation was concealed in sealed study folders that were held in a central , secured location until after informed consent was obtained . The nurses who scheduled the study visits did not have access to the r and omization list , and laboratory staff did not know the participants ' group assignments . Staff members involved in the intervention were aware of group assignments , but those who assessed achievement of the primary outcome were blinded to the intervention . Participants received no financial compensation or gifts . Dietary Interventions We r and omly assigned patients to a low-carbohydrate MED diet or to a low-fat diet . The MED diet was rich in vegetables and whole grains and low in red meat , which was replaced with poultry and fish . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 50 % of calories from complex carbohydrates , based on evidence that , in the context of a MED diet , a carbohydrate content less than 50 % of daily energy is more beneficial than higher content for weight loss and cardiovascular risk reduction ( 14 ) . The diet had no less than 30 % calories from fat . The main source of added fat was 30 to 50 g of olive oil . The low-fat diet was based on American Heart Association guidelines ( 15 ) ; it was rich in whole grains and restricted additional fats , sweets , and high-fat snacks . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 30 % of calories from fat and no more than 10 % of calories from saturated fat . Nutritionists and dietitians gave dietary advice to participants in both groups in monthly sessions in the first year and bimonthly sessions thereafter . Participants kept diet diaries after being instructed how to record their intake using food models as examples of portion size and using actual weights or amounts in terms of common measures ( such as cups , teaspoons , and dessert spoons ) . We assessed adherence to the diets by session attendance and review of the diaries . Nondietary Interventions Patients in both groups also received guidance on increasing their level of physical activity , mainly walking for a minimum of 30 minutes per day , but also swimming or aerobic ball games . The physical activity program relied heavily on home-based exercise with gradual progression toward a goal of 175 minutes of moderate-intensity physical activity per week . Although walking was encouraged , participants were allowed to choose other types of moderate-intensity physical activity , and programs were tailored on the basis of the results of a baseline physical fitness test and safety concerns . We asked all patients to record occupational , household , and leisure time physical activity . Outcomes We followed patients for 4 years to assess trial outcomes . The primary outcome measure was time to introduction of antihyperglycemic drug therapy . Trial investigators were responsible for initiating drug therapy by the following protocol . As suggested by the ADA for clinical evaluation and management of diabetic patients ( 16 ) , we measured HbA1c at baseline and every 3 months thereafter . Participants who had a HbA1c level greater than 7 % were given an additional 3 months to reinforce dietary guidance and physical activity ; if the HbA1c level remained greater than 7 % , a drug regimen was introduced . Participants with an HbA1c level greater than 7 % at baseline were counted as having experienced the primary outcome if they still had that level at first follow-up . Trial investigators were also responsible for initiating or titrating antihypertensive or lipid-lowering therapy . Secondary outcome measures were changes in weight ( including BMI and waist circumference ) , glycemic control ( HbA1c , glucose , serum insulin , and adiponectin levels and homeostasis model assessment of insulin sensitivity ) , coronary risk factors ( lipid levels and blood pressure ) , and medications and meeting ADA coronary risk factor goals ( HbA1c level weighed without shoes and in lightweight clothing to the nearest 0.1 kg at baseline and every month . Height at baseline ( for calculation of BMI ) was measured to the nearest millimeter with the use of a wall-mounted stadiometer ( Seca , Hamburg , Germany ) . Waist circumference was measured halfway between the last rib and the iliac crest . We measured HbA1c levels with high-pressure liquid chromatography by using the fully automated Glycosylated Hemoglobin Analyzer System ( Bio-Rad , Hercules , California ) traceable to the Diabetes Control and Complications Trial reference method , with a reference range of 4.0 % to 6.0 % . Insulin sensitivity in the fasting state was assessed with homeostasis model assessment and calculated with the following formula , as described by Matthews and colleagues ( 17 ) : fasting plasma glucose (mmol/L)fasting serum insulin (U/mL)/25 . High scores indicate low insulin sensitivity ( insulin resistance ) . We assayed plasma insulin and adiponectin levels by radioimmunoassay , as described elsewhere ( 18 ) . We performed assays for serum", "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", "Background / Objectives : While type II diabetes ( DM ) is a major cause of morbidity in the United States , limited data are available on the association between nut intake and incident DM . We sought to examine the association between nut consumption and the risk of DM.Subjects/ Methods : Prospect i ve cohort of 20 224 male participants of the Physicians ’ Health Study I. Nut consumption was estimated using a 19-item brief food frequency question naire , and incident DM was ascertained through yearly follow-up question naires . Cox regression was used to estimate relative risks of DM . Results : The average age of the study participants was 54.4±9.4 years ( range : 40.7–87.1 ) . During a mean follow-up of 19.2 years , 1828 cases of DM occurred . The crude incidence rates of DM were 4.82 , 4.85 , 4.92 , 4.16 , 4.29 and 3.32 cases per 1000 person-years for individuals reporting nut consumption of rarely/never , While nut consumption was associated with a lower risk of DM in a model adjusted for age ( P for tend 0.017 ) , such relation was attenuated on additional control for other confounders ( multivariable adjusted hazard ratios ( 95 % confidence interval ) for DM were 1.0 ( reference ) , 1.06 ( 0.93–1.20 ) , 1.10 ( 0.95–1.26 ) , 0.97 ( 0.82–1.14 ) , 0.99 ( 0.76–1.30 ) and 0.87 ( 0.61–1.24 ) from the lowest to the highest category of nut consumption , respectively ( P for trend 0.99 ) . No statistically significant association between nut consumption and DM was found in either lean or overweight/obese participants . Conclusions : Our data do not show an association between nut consumption and incident DM in US male physicians", "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", "BACKGROUND The nature of dietary fats and fasting concentrations of triglycerides affect postpr and ial hypertriglyceridemia and glucose homeostasis . OBJECTIVES The objectives were to examine the effects of meals enriched in monounsaturated fatty acids ( MUFAs ) or saturated fatty acids ( SFAs ) on postpr and ial lipid , glucose , and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations . DESIGN Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals ( ≈10 kcal/kg body weight ) containing MUFAs , SFAs , or no fat . Blood sample s were collected at baseline and hourly over 8 h for analysis . RESULTS The high-fat meals significantly increased postpr and ial concentrations of triglycerides , nonesterified fatty acids , and insulin and postpr and ial indexes of β cell function . However , postpr and ial indexes of insulin sensitivity decreased significantly . These effects were significantly attenuated with MUFAs relative to SFAs . CONCLUSIONS MUFAs postpr and ially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations . These data suggest that , in contrast with SFAs , MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges", "OBJECTIVE Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test ( OGTT ) . However , the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique . In this study , we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique . RESEARCH DESIGN AND METHODS In this study , 153 subjects ( 66 men and 87 women , aged 18 - 71 years , BMI 20 - 65 kg/m2 ) with varying degrees of glucose tolerance ( 62 subjects with normal glucose tolerance , 31 subjects with impaired glucose tolerance , and 60 subjects with type 2 diabetes ) were studied . After a 10-h overnight fast , all subjects underwent , in r and om order , a 75-g OGTT and a euglycemic insulin clamp , which was performed with the infusion of [3 - 3H]glucose . The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis . RESULTS The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp ( r = -0.02 , NS ) . From the OGTT , we developed an index of whole-body insulin sensitivity ( 10,000/square root of [ fasting glucose x fasting insulin ] x [ mean glucose x mean insulin during OGTT ] ) , which is highly correlated ( r = 0.73 , P glucose disposal during the euglycemic insulin clamp . CONCLUSIONS Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT . Our results demonstrate the limitations of such an approach . We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT", "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" ]

[ "The present investigation compared responses in previously identified physiological , biochemical , and psychological markers of overreaching in triathletes . Sixteen experienced male triathletes ( .VO(2max ) [ mean + /- SD ] = 55.7 + /- 4.9 mL . kg ( -1 ) . min ( -1 ) , age = 31.3 + /- 11.7 yr ) were divided into matched groups according to physical and performance characteristics , and were r and omly assigned to either intensified training ( IT ) or normal training ( NT ) groups . Physiological , biochemical , and psychological measures were taken at baseline , following four weeks of overload training and following a two-week taper . The IT group completed 290 % greater physical training load than the NT group during the overload period . The subjects completed a 3-km run time trial ( 3-km RTT ) each week in order to assess the time course of change in endurance performance . 3-km RTT performance was significantly reduced ( 3.7 + /- 7.5 % ; p 3-km RTT performance significantly improved in the NT group ( 3.0 + /- 1.1 % ; p 3-km RTT performance significantly improved in the IT group ( 7.0 + /- 5.6 % ; p Hemoglobin concentration significantly decreased and urea increased in both groups during the overload period ( p hemoglobin normalized with a greater increase in the IT group compared to the NT group ( p free testosterone to cortisol ratio was also observed in the IT group compared to the NT group during the taper ( p biochemical variables during the period of investigation . The RESTQ-76 Sport question naire showed an impaired recovery-stress state with increased training load , which improved following the taper in the IT group ( p athletes in a practical training setting", "The aim of this study was to identify indicators of non-functional overreaching ( NFOR ) in team sport athletes undertaking intensive training loads . Eighteen semi-professional rugby league players were r and omly assigned into two pair matched groups . One group completed 6 weeks of normal training ( NT ) whilst the other group was deliberately overreached through intensified training ( IT ) . Both groups then completed the same 7-day stepwise training load reduction taper . Multistage fitness test ( MSFT ) performance , $ $ \\ifmmode\\exp and after\\dot\\else\\exp and after\\.\\fi{V}{\\text{O}}_{{2\\max } } $ $ , peak aerobic running velocity ( Vmax ) , maximal heart rate , vertical jump , 10-s cycle sprint performance and body mass were measured pre- and post-training period and following the taper . Hormonal , haematological and immunological parameters were also measured pre-training and following weeks 2 , 4 and 6 of training and post-taper . MANOVA for repeated measures with contrast analysis indicated that MSFT performance and $ $ \\ifmmode\\exp and after\\dot\\else\\exp and after\\.\\fi{V}{\\text{O}}_{{2\\max } } $ $ were significantly reduced in the IT group over time and condition , indicating that a state of overreaching was attained . However , the only biochemical measure that was significantly different between the IT and NT group was the glutamine to glutamate ( Gln/Glu ) ratio even though testosterone , testosterone to cortisol ( T/C ) ratio , plasma glutamate , and CK activity were significantly changed after training in both groups . Positive endurance and power performance changes were observed post-taper in the IT group confirming NFOR . These changes were associated with increases in the T/C ratio and the Gln/Glu ratio and decreases in plasma glutamate and CK activity . These results indicate that although there was no single reliable biochemical marker of NFOR in these athletes , the Gln/Glu ratio and MSFT test may be useful measures for monitoring responses to IT in team sport athletes ", "Objective To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching ( NFOR ) . Design A prospect i ve case-control study using a monthly performance monitor with a st and ardised field test to detect the performance changes . Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones . Setting Sporting field and sports medical laboratory . Participants Ninety-four young elite soccer players were monitored during the 2006–2008 seasons . Twenty-one players were invited to the laboratory , seven of whom showed a significant performance decrease . Main outcome measures Performance change over time , scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone ( ACTH ) , growth hormone ( GH ) and cortisol . Results Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching . Scores were higher on depression and anger , whereas the resting GH levels and ACTH levels after maximal exercise were reduced . ACTH and GH were capable of classifying all but one player correctly as either NFOR or control . Conclusions Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR . Performance , mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players", "The aim of the present prospect i ve longitudinal study was to investigate the hormonal response in overtrained athletes at rest and during exercise consisting of a short-term exhaustive endurance test on a cycle ergometer at an intensity 10 % above the individual anaerobic threshold . Over a period of 19+/-1 months , 17 male endurance athletes ( cyclists and triathletes ; age 23.4+/-1.6 yr ; VO2max . 61.2+/-1.8 mL x min(-1 ) x kg(-1 ) ; means+/-SEM ) were examined five times on two separate days under st and ardized conditions . Short-term overtraining states ( OT , N=15 ) were primarily induced by an increase of frequency of high-intensive bouts of exercise or competitions without increase of the total amount of training . OT was compared with normal training states intraindividually ( NS , N=62 ) . During OT , the time to exhaustion of the exercise test was significantly decreased by 27 % on average . At rest and during exercise , the concentrations in plasma and the nocturnal excretion in urine of free epinephrine and norepinephrine were not significantly changed during OT . At physical rest , the concentrations of ( free ) testosterone , cortisol , luteinizing hormone , follicle-stimulating hormone , adrenocorticotropic hormone , growth hormone , and insulin during OT were comparable with those during NS . A significantly ( P maximal exercise-induced increase of the adrenocorticotropic hormone and growth hormone , as well as a trend for a decrease of cortisol ( P=0.060 ) and insulin ( P=0.036 ) , was measured . The response of free catecholamines as well as the ergometric performance of an all-out 30-s test was unchanged . Serum urea , uric acid , ferritin , and activity of creatine kinase showed no differences between conditions . In conclusion , the results confirm the hypothesis of a hypothalamo-pituitary dysregulation during OT expressed by an impaired response of pituitary hormones to exhaustive short-endurance exercise", "Objective To study whether field performance tests can make a valid distinction between non-functionally overreaching ( NFO ) athletes and control athletes . Design Monthly field performance tests were used to determine a performance decrement ( PD ) throughout a season . Athletes with a minimum of 1 month PD were compared with control athletes without a PD on mood characteristics and resting levels of stress hormones . Setting Sporting field and sports medical laboratory . Participants 129 young elite athletes , 77 soccer players and 52 middle-long distance runners were followed prospect ively during the 2006–2007 season . Fifteen of them were invited to the laboratory . Eight athletes showed a performance decrease lasting longer than 1 month , and seven athletes without a performance decrease acted as their controls . Main outcome measures Performance changes over time were measured using field tests . Profile of Mood States and resting levels of adrenocorticotrophic hormone ( ACTH ) and cortisol in blood were measured in the laboratory . Results PD athletes showed several symptoms typical of the non-functional state of overreaching ( OR ) . The PD group scored higher on depression and anger than controls . They also showed a specific pattern of correlations between negative mood subscales ( tension , fatigue and depression ) , which was absent in controls . ACTH levels at rest were similar , but lower cortisol levels in PD athletes pointed at a blunted cortisol response . Cortisol levels were decoupled from ACTH levels only in PD athletes . Conclusions Implementing performance-related criteria in field tests can help coaches and sports physicians to distinguish NFO athletes from athletes with balanced workload and recovery", "The purpose of the study was to investigate whether severe fatigue , possibly leading to overreaching , could be diagnosed at an early stage by a combination of parameters . Seven well-trained male subjects ( age [ mean + /- SD ] : 25.3 + /- 4.7 yr ; body mass : 76 + /- 6.6 kg ; VO2max : 61.1 + /- 7 ml.kg(-1).min(-1 ) ) increased their training load by doubling their training volume and increasing the intensity by 15 % over a period of two weeks . Before and after this intensified training period subjects underwent a series of tests including a maximal incremental cycle ergometer test ( Wmax ) with continuous ventilatory measurements and blood lactate values , time trial , basal blood parameter tests ( red and white blood profile ) , hormones [ growth hormone ( GH ) , insulin-like growth factor 1(IGF-1 ) , adreno-corticotropic hormone ( ACTH ) , cortisol ] , neuro-endocrine stress test [ short insulin tolerance test ( SITT ) , combined anterior pituitary test ( CAPT ) and exercise ] , a shortened Profile of Mood State ( POMS ) , the estimated rate of perceived exertion ( RPE ) and a cognitive reaction time test . The intensified training period result ed in a significant increase of the training load ( p training monotony ( p training strain ( p RPE during training increased significantly ( p Total mood score obtained from the POMS tended to increase ( p=0.06 ) , reflecting an increase in worse mood state . A novel finding was that reaction times increased significantly , indicating that overreaching might adversely affect speed of information processing by the brain , especially for the most difficult conditions . After the intensified training period , neither changes in exercise-induced plasma hormone values , nor SITT values were observed . During the CAPT only cortisol showed a significant decrease after the intensified training period . Hemoglobin showed a significant decrease after the intensified training period whereas hematocrit , red blood cell count ( RBC ) and MCV tended to decrease . The intensified training had no effect on physical performance ( Wmax or time trial ) , maximal blood lactate , maximal heart rate and white blood cell profile . The most sensitive parameters for detecting overreaching are reaction time performance ( indicative for cognitive brain functioning ) , RPE and to a lesser extend the shortened POMS . This strongly suggests , that central fatigue precedes peripheral fatigue . All other systems , including the neuro-endocrine , are more robust and react most likely at a later stage in exhaustive training periods", "Seventeen weight-trained males were divided into an overtraining group [ OT ; n = 11 ; age = 22.0 + /- 0.9 ( SE ) yr ] that weight trained their legs daily for 2 wk with 100 % 1 repetition maximum relative intensity on a squat machine and a control group ( n = 6 ; age = 23.7 + /- 2.4 yr ) that exercised 1 day/wk with low relative intensity ( 50 % 1 repetition maximum ) . Test batteries including strength assessment s and resting and exercise-induced concentrations of epinephrine and norepinephrine were conducted at the beginning , middle , and end ( tests 1 - 3 , respectively ) of the study . Strength capabilities decreased by test 3 for the OT group ( P Resting catecholamine concentrations did not change for either group during the study , whereas exercise-induced concentrations of both epinephrine ( test 1 = 3,407.9 + /- 666.6 pmol/l , test 2 = 7,563.7 + /- 1,210.6 pmol/l , test 3 = 6,931.6 + /- 919.3 pmol/l ) and norepinephrine ( test 1 = 42.9 + /- 7.4 nmol/l , test 2 = 70.0 + /- 8.8 nmol/l , test 3 = 85.2 + /- 14.5 nmol/l ) significantly increased by tests 2 and 3 for only the OT group . Correlation coefficients suggested decreased responsitivity of skeletal muscle to sympathetic nervous system activity . It appears that altered exercise-induced sympathetic nervous system activity accompanies high relative intensity resistance exercise overtraining and may be among the initial responses to the onset of the previously theoretical sympathetic overtraining syndrome", "In the literature the use of plasma levels of cortisol and the testosterone and testosterone : cortisol ratio for training management is encouraged . Decreased levels of testosterone and increased levels of cortisol are suggested to be indicative for a disturbance in the anabolic-catabolic balance , which may express itself in decreased performance . The purpose of the study was to examine if the acute hormonal response to a bout of exercise and the resting levels of testosterone , luteinizing hormone ( LH ) and cortisol are correlated to performance in cyclists . In addition , the effect of training on this correlation was studied . Ten professional cyclists participated and measurements took place before and after a defined period of training . Maximum workload ( Pmax ) , determined on a cycle-ergometer with a slowly increasing protocol , increased by 30 watt ( p Workload at a lactate level of 4 mmol/l ( P4 ) increased by 18 watt ( p resting testosterone levels decreased from 28.8 + /- 74 nmol/l to 24.6 + /- 90 nmol/l ( p Resting cortisol levels increased from 272 + /- 110 nmol/l pre training to 379 + /- 242 nmol/l post training ( p catabolic state . The acute hormonal response and the resting levels of LH were not changed post training . The resting levels of testosterone and cortisol and the acute response to exercise showed no correlation with performance pre and post training . In spite of an increased catabolic state post training there was an increase in performance . These results suggest that in endurance trained cyclists , decreased testosterone levels , increased cortisol levels and a decreased testosterone : cortisol ratio does not automatically lead to a decrease in performance or a state of overtraining", "The effectiveness of high performance training should be examined at short intervals in order to recognize overtraining promptly . Field or laboratory tests can usually not be performed with such frequency . Easy-to-measure biological , training-relevant parameters are being sought to use in their place . Since the importance of the sympathetic nervous system for adaptation of stress and the relationship between physical training and the activity of the sympathetic nervous system are well accepted , and since an impairment of the sympathetic nervous system is assumed in an overtraining syndrome , we examined the relevance of nocturnal \" basal \" urinary excretion of free catecholamines with respect to its practical application : 1 . during a pilot study ( training of road and track cyclists before the 1988 Olympic Games in Seoul ) , 2 . through a 4-week prospect i ve , experimental study in 1989 and 1990 ( middle- and long-distance runners ) , 3 . during the competitive season and winter break of a soccer team between August 1990 and April 1991 . The following hypothesis was made : An overtraining or exhaustion syndrome in athletes may usually be accompanied by at least a 50 % decrease in basal dopamine , noradrenaline and adrenaline excretion . When training is effective or the athletes are not exhausted , the decrease of the excretion rate -- with the exception of dopamine -- is more likely to be lower ( noradrenaline , adrenaline ) . Generalization of these results requires further expansion of the experimental basis", "In overtrained athletes , several signs and symptoms have been associated with the imbalance between training and recovery . However , reliable diagnostic markers for distinguishing between well-trained , overreached ( OR ) and overtrained ( OT ) athletes are lacking . A hallmark feature of overtraining syndrome ( OTS ) is the inability to sustain intense exercise and recover for the next training or competition session . We therefore devised a test protocol utilizing two bouts of maximal work . With this test protocol we tried to establish a difference in hormonal responses between the training status of T and OR athletes . Seven well-trained cyclists participated in this study and were tested before and after a training camp . We also present the data of one OT motocross athlete who was clinical ly diagnosed as overtrained . All athletes performed two maximal exercise tests separated by 4 h. Blood was analyzed for cortisol , adrenocorticotrophic hormone ( ACTH ) , growth hormone and prolactin ( PRL ) . Performance decreased by 6 % between the first and the second exercise test in the OR group and by 11 % in the OT subject . Moreover , during the second exercise test there were more marked differences between the T and OR athletes ; in particular , the OT subject did not show an increase in some of the hormonal responses . PRL increased only by 14 % in the OT subject ’s second test and there was a 7 % decrease in ACTH . The two exercise approach enables us to detect subtle performance decrements that will not be identified by one exercise trigger . The hormonal responses to the second exercise test were different between the T and OR athletes ( the increase in the T group was higher than in the OR that was higher than in the OT ) . The results of the case presentation of an overtrained athlete provide evidence of an altered and dysfunctional hypothalamic – pituitary axis response to two bouts of maximal exercise . These findings can be used to develop markers for diagnosis of OTS and to begin to address the pathologic mechanism operative in the syndrome , as well as providing an outcome measure to evaluate possible therapeutic regimes", "Slivka , DR , Hailes , WS , Cuddy , JS , and Ruby , BC . Effects of 21 days of intensified training on markers of overtraining . J Strength Cond Res 24(10 ) : 2604 - 2612 , 2010-The purpose of this study was to impose a period of quantifiable intensified training to determine if commonly used diagnostic markers of overtraining parallel changes in physical performance and thus overtraining status . Eight trained male cyclists ( 24 ± 1 years , 71 ± 3 kg , & OV0312;O2peak = 4.5 ± 0.1·L·min−1 ) performed 21 days ( 3,211 km ) of intensified training in the field where volume and intensity were increased over normal training . Salivary IgA , testosterone , and cortisol , 1-hour time trial performance , heart rate response , and profile of mood states ( POMS ) were collected and analyzed throughout the 21-day training period . The POMS category vigor declined from day 1 to day 4 and remained lower throughout ( p changes in overtraining parameters . However , individuals who demonstrated 2 or more symptoms of overtraining at any point throughout the 21 days were considered symptomatic and had a lower ( p ) average workload during the initial 1-hour time trial ( 253 ± 5 vs. 288 ± 14 W ) . Interestingly , the 1-hour time trial power in these individuals with symptoms of overtraining did not decline ( p > 0.05 ) . These data demonstrate that markers of overtraining do not parallel a decrease in performance and should be interpreted with caution" ]

[ "INTRODUCTION The purpose of this study was to test the hypothesis that physical training ( PT ) , especially high-intensity PT , would have a favorable effect on components of the insulin resistance syndrome ( IRS ) in obese adolescents . METHODS Obese 13- to 16-yr-olds ( N = 80 ) were r and omly assigned to one of the following 8-month interventions ; 1 ) lifestyle education (LSE)-alone every 2 wk , 2 ) LSE+moderate-intensity PT , and 3 ) LSE+high-intensity PT . PT was offered 5 d x wk(-1 ) . Plasma triacylglycerol ( TAG ) , total cholesterol ( TC ) , high-density lipoprotein cholesterol ( HDLC ) , very low-density lipoprotein cholesterol ( VLDLC ) , low-density lipoprotein cholesterol ( LDLC ) , low-density lipoprotein ( low density lipoprotein ( LDL ) ) particle size , apolipoproteins AI and B , glucose , insulin , and blood pressure were measured with st and ardized methods . RESULTS The intent-to-treat analyses for all subjects who completed pre- and post-tests regardless of their adherence to the interventions showed that the LSE+high-intensity PT group had more favorable changes than the LSE-alone group in TAG level ( P = 0.012 ) , TC/HDLC ( P = 0.013 ) , and diastolic blood pressure ( P = 0.031 ) . For efficacy analyses , all PT subjects who attended at least 2 d x wk(-1 ) ( 40 % ) were combined into one group ( LSE+PT ) and compared with the LSE-alone group . These two-group analyses showed significant interactions ( P deltaTAG , deltaVLDLC , and deltaTC/HDLC , such that subjects who had the least favorable baseline values showed the most beneficial impact of the PT . Of particular interest was a favorable effect of the PT on LDL particle size . CONCLUSION PT , especially high-intensity PT , had a favorable effect on several IRS markers in obese adolescents", "OBJECTIVES The aim of this study was to determine the effects of physical activity on systemic blood pressure ( BP ) and early markers of atherosclerosis in pre-pubertal obese children . BACKGROUND Hypertension and endothelial dysfunction are premature complications of obesity . METHODS We performed a 3-month r and omized controlled trial with a modified crossover design : 44 pre-pubertal obese children ( age 8.9 + or - 1.5 years ) were r and omly assigned ( 1:1 ) to an exercise ( n = 22 ) or a control group ( n = 22 ) . We recruited 22 lean children ( age 8.5 + or - 1.5 years ) for baseline comparison . The exercise group trained 60 min 3 times/week during 3 months , whereas control subjects remained relatively inactive . Then , both groups trained twice/week during 3 months . We assessed changes at 3 and 6 months in office and 24-h BP , arterial intima-media thickness ( IMT ) and stiffness , endothelial function ( flow-mediated dilation ) , body mass index ( BMI ) , body fat , cardiorespiratory fitness ( maximal oxygen consumption [ VO(2)max ] ) , physical activity , and biological markers . RESULTS Obese children had higher BP , arterial stiffness , body weight , BMI , abdominal fat , insulin resistance indexes , and C-reactive protein levels , and lower flow-mediated dilation , VO(2)max , physical activity , and high-density lipoprotein cholesterol levels than lean subjects . At 3 months , we observed significant changes in 24-h systolic BP ( exercise -6.9 + or - 13.5 mm Hg vs. control 3.8 + or - 7.9 mm Hg , -0.8 + or - 1.5 st and ard deviation score [ SDS ] vs. 0.4 + or - 0.8 SDS ) , diastolic BP ( -0.5 + or - 1.0 SDS vs. 0 + or - 1.4 SDS ) , hypertension rate ( -12 % vs. -1 % ) , office BP , BMI z-score , abdominal fat , and VO(2)max . At 6 months , change differences in arterial stiffness and IMT were significant . CONCLUSIONS A regular physical activity program reduces BP , arterial stiffness , and abdominal fat ; increases cardiorespiratory fitness ; and delays arterial wall remodeling in pre-pubertal obese children . ( Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children : A R and omized Controlled Trial ; NCT00801645 )", "Aims : To evaluate effects of a low energy diet , with or without strength training , on blood lipid profile in obese children . Methods : Eighty two obese children were enrolled into a six week dietary programme , and were r and omly allocated to a training group or a non-training group . The training group underwent regular exercise sessions with emphasis on strength training . Results : Height increased significantly , with a non-significant reduction in body mass index . Fat free mass increased significantly in the training group . Serum total cholesterol was significantly reduced in both groups . The LDL : HDL ratio significantly decreased in the training group . Conclusion : Results support the potentially beneficial effects of both diet and physical training . Further and longer term evaluation of such programmes is required", "INTRODUCTION Developing effective exercise programmes for the paediatric population is a strategy for decreasing obesity and is expected to help in eventually limiting obesity-associated long-term health and societal impact . In this study , the effects of a 12-week twice weekly additional exercise training , which comprised a combination of circuit-based resistance training and aerobic exercises , in additional to typical physical education sessions , on aerobic fitness , body composition and serum C-reactive protein ( CRP ) and lipids were analysed in 13- to 14-year-old obese boys contrasted with a control group . MATERIAL S AND METHODS Both the exercise group ( EG , n = 12 ) and control group ( CG , n = 12 ) participated in the typical 2 sessions of 40-minute physical education ( PE ) per week in schools , but only EG participated in additional 2 sessions per week of 45 to 60 minutes per session of exercise training , which comprised a combination of circuit-based resistance training and aerobic exercises maintained at 65 % to 85 % maximum heart rate ( HRmax = 220 - age ) . Body composition was measured using dual energy X-ray absorptiometry ( DEXA ) . Fasting serum CRP and blood lipids were analysed pre- and postexercise programme . Aerobic fitness was measured by an objective laboratory submaximal exercise test , PWC170 ( Predicted Work Capacity at HR 170 bpm ) . RESULTS Exercise training significantly improved lean muscle mass , body mass index , fitness , resting HR , systolic blood pressure and triglycerides in EG . Serum CRP concentrations were elevated at baseline in both groups , but training did not result in a change in CRP levels . In the CG , body weight increased significantly at the end of the 12-week period . CONCLUSION This study supports the value of an additional exercise training programme , beyond the typical twice weekly physical education classes , to produce physiological benefits in the management of obesity in adolescents , including prevention of weight gain", "This prospect i ve , r and omized study investigated the effect of exercise on leptin , insulin , cortisol and lipid profiles in obese children . A total of 40 obese boys aged 10 - 12 years with a body mass index ( BMI ) ≥ 30 kg/m2 were r and omly separated into an exercise group ( n = 20 ) that underwent a 12-week aerobic exercise programme and a non-exercise ( control ) group ( n = 20 ) . The BMI , low-density lipoprotein , cortisol , leptin and insulin levels were significantly lower in the exercise group after 12 weeks compared with baseline values , whereas high-density lipoprotein levels were significantly higher . In contrast , in the control group , low-density lipoprotein , cortisol and leptin levels were significantly higher after 12 weeks compared with baseline values while high-density lipoprotein levels were significantly lower . These findings indicate the importance of regular exercise in the regulation of body weight and protection against cardiovascular risk factors in obese children", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "OBJECTIVE : To determine the effect of exercise training ( ET ) on components of the insulin resistance syndrome ( IRS ) in obese children . DESIGN : R and omized , modified cross-over study , with subjects assigned to one of two conditions : ( 1 ) 4 months of ET followed by 4 months of no-ET ; or ( 2 ) 4 months of no-ET followed by 4 months of ET . Measurements were made at three time points : 0 , 4 and 8 months . SUBJECTS : 79 obese , but otherwise healthy children ( age : 7–11 y , percent fat ( % fat ) 27–61 % ) . MEASUREMENTS : Plasma lipid and lipoprotein concentrations , plasma insulin and glucose concentrations ; % fat ; submaximal heart rate ( HR ) as an index of fitness . EXERCISE TRAINING : ET was offered 5 d/week 40 min/d . For the 73 children who completed 4 months of ET , the mean attendance was 80 % ( that is , 4 d/week ) and the average HR during ET was 157 bpm . RESULTS : Significant ( P for plasma triglyceride ( TG ) and insulin concentrations and % fat . The average change for both groups , from just before ET to just after the 4 month ET was −0.24 mmolċl−1 for TG , −25.4 pmolċl−1 for insulin and −1.6 units for % fat . When Group 1 ceased ET , over the following 4 month period the average change for insulin was + 26.6 pmolċl−1 and for % fat + 1.3 units . CONCLUSION : Some components ( plasma TG , insulin , % fat ) of the IRS are improved as a result of 4 months of ET in obese children . However , the benefits of ET are lost when obese children become less active", "OBJECTIVES The present study aim ed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation ( FMD ) carotid intima-media thickness ( IMT ) and cardiovascular risk factors ( RF ) . BACKGROUND Childhood obesity contributes to adult obesity and subsequent cardiovascular disease . Physical inactivity is a major RF for obesity , endothelial dysfunction , and elevated carotid IMT , culminating in early atherosclerotic disease . METHODS Sixty-seven obese subjects ( age 14.7 + /- 2.2 years ) were r and omly assigned to 6 months ' exercise or non-exercise protocol . We examined the influence of exercises ( 1 h , 3 times/week ) on FMD , IMT , and cardiovascular risk profile . RESULTS Compared with lean control subjects , obese children demonstrated at baseline significantly impaired FMD ( 4.09 + /- 1.76 % vs. 10.65 + /- 1.95 % , p increased IMT ( 0.48 + /- 0.08 mm vs. 0.37 + /- 0.05 mm , p obesity-related cardiovascular RF . Significant improvements were observed in the exercise group for IMT ( 0.44 + /- 0.08 mm , p = 0.012 , -6.3 % ) and FMD ( 7.71 + /- 2.53 % , p body mass index st and ard deviation scores , body fat mass , waist/hip ratio , ambulatory systolic blood pressure , fasting insulin , triglycerides , low-density lipoprotein/high-density lipoprotein ratio , and low-degree inflammation ( C-reactive protein , fibrinogen ) . CONCLUSIONS The present study documented increased IMT , impaired endothelial function , and various elevated cardiovascular RF in young obese subjects . Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children", "OBJECTIVES Atherosclerosis is a disease that begins in childhood ; endothelial dysfunction is its earliest detectable manifestation , and primary prevention strategies are likely to be most effective if instituted early . The aim of this study was to characterize the impact of obesity on vascular function in young children and to determine whether an exercise program improves abnormalities in vascular function . STUDY DESIGN The influence of 8 weeks of exercise training was examined in 14 obese subjects , 8.9 + /- 0.4 years of age , with the use of a r and omized crossover protocol . Conduit vessel endothelial function was assessed by means of high-resolution ultrasound and flow-mediated dilation of the brachial artery ( FMD ) . RESULTS Exercise training did not change subcutaneous fat mass , body weight , or body mass index . FMD in the obese group was significantly impaired relative to matched control subjects at entry ( 6.00 % + /- 0.69 % to 12.32 % + /- 3.14 % , P FMD significantly improved with exercise training ( 7.35 % + /- 0.99 % , P Conduit vessel FMD , a vali date d surrogate measure of early atherosclerosis , was impaired in obese children but improved as a result of exercise training . This study supports the value of an exercise program in the treatment of obese children in a primary prevention setting", "BACKGROUND The Child and Adolescent Trial for Cardiovascular Health is a school-based study design ed to test the effectiveness of dietary , physical activity , and educational interventions for reducing cardiovascular disease risk and teaching healthful behaviors to children . METHODS As part of a pilot phase in 1989 , lipid , lipoprotein , and anthropometric measures were taken in black ( n = 90 ) , Hispanic ( n = 68 ) , and white ( n = 265 ) 8- to 10-year-old schoolchildren in California , Louisiana , Minnesota , and Texas . RESULTS There were no significant differences in mean lipoprotein cholesterol values between fasting and nonfasting children . Therefore data from fasting and nonfasting children were pooled . Males and females within the same ethnic groups had similar mean levels of total cholesterol , low-density lipoprotein cholesterol , and very low-density lipoprotein cholesterol . However , levels of high-density lipoprotein cholesterol were higher among white and black males than among females from the same ethnic groups . Black males had higher total cholesterol than white males and higher high-density lipoprotein cholesterol than white males and Hispanic males . Similarly , black females had higher high-density lipoprotein cholesterol than white and Hispanic females . In all children combined high-density lipoprotein cholesterol was inversely correlated and low-density lipoprotein cholesterol was positively correlated with subscapular and tricep skinfold thickness , weight , and body mass index . There were significant differences in mean lipoprotein cholesterol levels between geographic sites . Total cholesterol , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol were highest in children from California followed by children from Texas , Minnesota , and Louisiana . CONCLUSION Our results suggest that body fatness total cholesterol , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol differ in children by gender , ethnicity , and geographic location", "PURPOSE To study the effect of exercise volume on pre- and early-pubertal children 's lipid-lipoprotein profile . METHODS Thirty-four children ( 15 girls ) completed 12 wk of exercise training , preceded by a 12-wk control period . Sixteen ( 7 girls and 9 boys ) expended an additional 422 + /- 5 kJ.kg BM ( LOW , 100 kcal.kg ) , whereas 18 ( 8 girls and 10 boys ) expended an additional 586 + /- 7 kJ.g ( MOD , 140 kcal.kg ) as a result of the training program . They all exercised on three nonconsecutive days per week at 80 + /- 1 % HRpeak . Exercise duration was individualized to match energy expenditure targets . Plasma TG , TC , and HDL-C were measured precontrol , pretraining , and posttraining . LDL-C , TC/HDL-C , and LDL-C/HDL-C were also calculated . RESULTS Group mean lipid-lipoprotein concentrations did not change as a result of training energy expenditure in either of the groups ( P > 0.05 ) . Dietary composition , habitual physical activity , and body composition were also relatively stable over the intervention period ( P > 0.05 ) . In the LOW , but not the MOD group , peak VO2 ( mL.kg.min ) tended to increase over the intervention period ( P = 0.07 ) . Pearson 's product moment correlation analyses indicated that pretraining concentrations of TG , TC , LDL-C , TC/HDL-C , and LDL-C/HDL-C were all related to the small changes seen in the lipid-lipoprotein profile ( P aerobic exercise training over a 12-wk period , did not cause significant alterations in the lipid-lipoprotein profile in pre- and early-pubertal children . This may indicate that the exercise volume was insufficient , the lipoprotein profiles of the majority of children in this study were classified as \" desirable , \" or more likely a combination of these factors" ]

[ "Reduced maternal thyroid hormone concentrations during pregnancy can adversely affect fetal neurological development . In the context of national iodine supplementation programmes , concern has been expressed over the theoretical possibility that iodine supplementation during pregnancy might adversely affect fetal development as a result of maternal thyroid inhibition from the Wolff-Chaikoff effect . In a double blind controlled trial in five villages in Papua New Guinea , several measures of motor and cognitive function showed no significant differences at either age 11 or 15 years between those children whose mothers had received supplementary iodine during pregnancy and the control children whose mothers had received the placebo", "Abstract Endemic cretinism is characterised by multiple neurological defects including deaf-mutism , diplegia , squint , and mental deficiency . The condition is widely prevalent in the Highl and s of New Guinea in association with severe iodine deficiency . Previous studies have shown that iodised oil provides a very satisfactory correction of severe iodine deficiency in New Guinea . A controlled trial on the use of intramuscular iodised oil in the prevention of endemic cretinism was carried out in the Western Highl and s of New Guinea and involved a population of approximately 8000 . Subsequent follow-up over four years revealed 26 endemic cretins out of a total of 534 children born to mothers who had not received iodised oil ; the mothers of 5 of these cretins were pregnant at the start of the trial . In comparison , 7 cases of endemic cretinism occurred among 498 children born to mothers who had been treated with iodised oil ; in 6 of these 7 cases , the mother was pregnant when the trial commenced . It is concluded that intramuscular iodised oil is effective in the prevention of endemic cretinism and that , for it to be effective , it should be given prior to conception . This suggests that severe iodine deficiency in the mother produces neurological damage during fetal development", " One hundred and eighty euthyroid pregnant women were selected at the end of the first trimester of gestation on the basis of biochemical criteria of excessive thyroid stimulation , defined as supranormal serum thyroglobulin ( TG > 20 micrograms/L ) associated with a low normal free T4 index ( 25 x 10(-3 ) ) . Women were r and omized in a double blind protocol into three groups and treated until term with a placebo , 100 micrograms potassium iodide (KI)/day , or 100 micrograms iodide plus 100 micrograms L-T4/day . Parameters of thyroid function , urinary iodine excretion , and thyroid volume were monitored sequentially . Neonatal thyroid parameters , including thyroid volume by echography , were also assessed in the newborns from mothers of the three groups . In women receiving a placebo , the indices of excessive thyroid stimulation worsened as gestation progressed , with low free T4 levels , markedly increased serum TG and T3/T4 ratio . Serum TSH doubled , on the average , and was supranormal in 20 % of the cases at term . Urinary iodine excretion levels were low , around 30 micrograms/L at term . The thyroid volume increased , on the average , by 30 % , and 16 % of the women developed a goiter , confirming the goitrogenic stimulus associated with pregnancy . Moreover , the newborns of these mothers had significantly larger thyroid volumes at birth as well as elevated serum TG levels . In both groups of women receiving an active treatment , the alterations in thyroid function associated with pregnancy were markedly improved . The increase in serum TSH was almost suppressed , serum TG decreased significantly , and changes in thyroid volume were minimized ( group receiving KI ) or almost suppressed ( group receiving KI combined with L-T4 ) . Moreover , in the newborns of the mothers in the two groups receiving an active treatment , serum TG was significantly lower , and thyroid volume at birth was normal . The effects of therapy were clearly more rapid and more marked in the group receiving a combination of T4 and KI than in the women receiving KI alone . The differences could be partly attributed to the slightly higher amount of iodine received by women in the combined treatment . However , the main benefits of the combined treatment were almost certainly attributable to the hormonal effects of the addition of L-T4 . Furthermore , the study demonstrated that the administration of T4 did not hamper the beneficial effect of iodine supplementation . In conclusion , the present work emphasizes the potential risk of goitrogenic stimulation in both mother and newborn in the presence of mild iodine deficiency . ( ABSTRACT TRUNCATED AT 400 WORDS", "The prevalence of iodine deficiency disorders and the thyroid status of the population were studied in an endemic goitre area in Algeria . After oral administration of lipiodol ( 0.5 ml ) , three treated groups of mother-newborn couples were compared to an untreated group : group A , mothers treated 1 - 3 months before conception ; group B , mothers treated during the first month of pregnancy ; group C , mothers treated during the third month of pregnancy . Untreated mothers were used as a control ( group D ) . After lipiodol treatment , all newborn babies and mothers were clinical ly euthyroid . All tested newborn babies were full term and no goitre was observed in the four groups . In the mothers , goitre prevalence and thyrotrophin levels decreased significantly , whereas maternal milk and urinary iodine and serum-free thyroxine levels were significantly higher after treatment . The rate of prematurity , stillbirths and abortions in the treated groups was reduced when compared to the untreated group , whereas placental and birth weights were significantly higher . In group D two cases of neonatal hypothyroidism were detected . Their re-evaluation confirmed that hypothyroidism was transient . Groups A , B and C were statistically different from group D with regard to neonatal thyrotrophin and thyroxine . Positive correlations were found between neonatal thyroxine and birth weights and placental weights on the one h and , and maternal urinary iodine and free thyroxine on the other . Consequently , these data indicate that oral administration of lipiodol before or during the first trimester of pregnancy normalizes thyroid function in newborn babies and mothers , increases placental and birth weight and reduces the frequency of iodine deficiency disorders . ( ABSTRACT TRUNCATED AT 250 WORDS", "Thyroid gl and size was ultrasonographically determined in 35 pregnant women who live in an area with moderate iodine deficiency . Iodide salt was administered to group A ( n = 17 ) , whereas group B ( n = 18 ) was used as a control . Each group was tested for thyroid-stimulating hormone serum levels , iodine excretion , and thyroid volume . In both groups thyroid-stimulating hormone levels were similar and did not change throughout pregnancy . The iodine excretion at the third trimester in the treated group was significantly ( p less than 0.01 ) higher than that of group B ( 100.0 + /- 39.0 versus 50.0 + /- 37.0 micrograms iodine per 24 hours , respectively ) . Initially , thyroid volume did not differ between the two groups . At the end of pregnancy , no difference was found in thyroid size in group A , whereas in the untreated women it increased significantly ( p less than 0.0001 ) with a mean increase of 1.6 + /- 0.6 ml ( 16.2 % + /- 6.0 % ) . These results show that the increased thyroid size in the control group was mainly a result of relative iodine deficiency and that iodoprophylaxis should be warranted even in areas with moderate iodine deficiency to prevent the increase in thyroid size and , probably , to avoid the risk of maternal and fetal hypothyroidism" ]

[ "BACKGROUND Epidemiological studies have shown television watching to be a risk factor for the development of obesity in children . The effect of reducing television watching and other sedentary behaviors as a component of a comprehensive obesity treatment program has not been thoroughly tested . OBJECTIVE To compare the influence of targeting decreases in sedentary behavior vs. increases in physical activity in the comprehensive treatment of obesity in 8- to 12-year-old children . DESIGN R and omized , controlled outcome study . SETTING Childhood obesity research clinic . DESIGN Ninety families with obese 8- to 12-year-old children were r and omly assigned to groups that were provided a comprehensive family-based behavioral weight control program that included dietary , and behavior change information but differed in whether sedentary or physically active behaviors were targeted and the degree of behavior change required . RESULTS Results during 2 years showed that targeting either decreased sedentary behaviors or increased physical activity was associated with significant decreases in percent overweight and body fat and improved aerobic fitness . Self-reported activity minutes increased and targeted sedentary time decreased during treatment . Children substituted nontargeted sedentary behaviors for some of their targeted sedentary behaviors . CONCLUSION These results support reducing sedentary behaviors as an adjunct in the treatment of pediatric obesity", "Background Schools are the most frequent target for intervention programs aim ed at preventing child obesity ; however , the overall effectiveness of these programs has been limited . It has therefore been recommended that interventions target multiple ecological levels ( community , family , school and individual ) to have greater success in changing risk behaviors for obesity . This study examined the immediate and short-term , sustained effects of the Switch program , which targeted three behaviors ( decreasing children 's screen time , increasing fruit and vegetable consumption , and increasing physical activity ) at three ecological levels ( the family , school , and community ) . Methods Participants were 1,323 children and their parents from 10 schools in two states . Schools were matched and r and omly assigned to treatment and control . Measures of the key behaviors and body mass index were collected at baseline , immediately post-intervention , and 6 months post-intervention . Results The effect sizes of the differences between treatment and control groups ranged between small ( Cohen 's d = 0.15 for body mass index at 6 months post-intervention ) to large ( 1.38 ; parent report of screen time at 6 months post-intervention ) , controlling for baseline levels . There was a significant difference in parent-reported screen time at post-intervention in the experimental group , and this effect was maintained at 6 months post-intervention ( a difference of about 2 hours/week ) . The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant . At the 6-month follow-up , parent-reported screen time was significantly lower , and parent and child-reported fruit and vegetable consumption was significantly increased . There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group . The intervention effects were moderated by child sex ( for fruit and vegetable consumption , physical activity , and weight status ) , family involvement ( for fruit and vegetable consumption ) , and child body mass index ( for screen time ) . The perception of change among the experimental group was generally positive with 23 % to 62 % indicating positive changes in behaviors . Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children 's fruit and vegetable consumption and minimizing screen time . The Switch program offers promise for use in youth obesity prevention", "OBJECTIVE To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grade s 6 to 8 . DESIGN R and omized , controlled field trial with 5 intervention and 5 control schools . Outcomes were assessed using preintervention ( fall 1995 ) and follow-up measures ( spring 1997 ) , including prevalence , incidence , and remission of obesity . PARTICIPANTS A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities . INTERVENTION Students participated in a school-based interdisciplinary intervention over 2 school years . Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education . Sessions focused on decreasing television viewing , decreasing consumption of high-fat foods , increasing fruit and vegetable intake , and increasing moderate and vigorous physical activity . MAIN OUTCOME MEASURES Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles . Because schools were r and omized , rather than students , the generalized estimating equation method was used to adjust for individual-level covariates under cluster r and omization . RESULTS The prevalence of obesity among girls in intervention schools was reduced compared with controls , controlling for baseline obesity ( odds ratio , 0.47 ; 95 % confidence interval , 0.24 - 0.93 ; P = .03 ) , with no differences found among boys . There was greater remission of obesity among intervention girls vs. control girls ( odds ratio , 2.16 ; 95 % confidence interval , 1.07 - 4.35 ; P = .04 ) . The intervention reduced television hours among both girls and boys , and increased fruit and vegetable consumption and result ed in a smaller increment in total energy intake among girls . Reductions in television viewing predicted obesity change and mediated the intervention effect . Among girls , each hour of reduction in television viewing predicted reduced obesity prevalence ( odds ratio , 0.85 ; 95 % confidence interval , 0.75 - 0.97 ; P = .02 ) . CONCLUSION Planet Health decreased obesity among female students , indicating a promising school-based approach to reducing obesity among youth", "OBJECTIVE To test a 2-year community- and family-based obesity prevention program for low-income African American girls : Stanford GEMS ( Girls ' health Enrichment Multi-site Studies ) . DESIGN R and omized controlled trial with follow-up measures scheduled at 6 , 12 , 18 , and 24 months . SETTING Low-income areas of Oakl and , California . PARTICIPANTS African American girls aged 8 to 10 years ( N=261 ) and their parents or guardians . INTERVENTIONS Families were r and omized to one of two 2-year , culturally tailored interventions : ( 1 ) after-school hip-hop , African , and step dance classes and a home/family-based intervention to reduce screen media use or ( 2 ) information-based health education . MAIN OUTCOME MEASURE Changes in body mass index ( BMI ) . RESULTS Changes in BMI did not differ between groups ( adjusted mean difference [ 95 % confidence interval ] = 0.04 [ -0.18 to 0.27 ] per year ) . Among secondary outcomes , fasting total cholesterol level ( adjusted mean difference , -3.49 [ 95 % confidence interval , -5.28 to -1.70 ] mg/dL per year ) , low-density lipoprotein cholesterol level ( -3.02 [ -4.74 to -1.31 ] mg/dL per year ) , incidence of hyperinsulinemia ( relative risk , 0.35 [ 0.13 to 0.93 ] ) , and depressive symptoms ( -0.21 [ -0.42 to -0.001 ] per year ) decreased more among girls in the dance and screen time reduction intervention . In exploratory moderator analysis , the dance and screen time reduction intervention slowed BMI gain more than health education among girls who watched more television at baseline ( P = .02 ) and /or those whose parents or guardians were unmarried ( P = .01 ) . CONCLUSIONS A culturally tailored after-school dance and screen time reduction intervention for low-income , preadolescent African American girls did not significantly reduce BMI gain compared with health education but did produce potentially clinical ly important reductions in lipid levels , hyperinsulinemia , and depressive symptoms . There was also evidence for greater effectiveness in high-risk subgroups of girls", "Objective : To assess the efficacy of a school-based intervention programme to reduce the prevalence of overweight in 6 to 10-year-old children . Design : Cluster-r and omized , controlled study .Subjects : A total of 3135 boys and girls in grade s 1–4 were included in the study . Methods : Ten schools were selected in Stockholm county area and r and omized to intervention ( n=5 ) and control ( n=5 ) schools . Low-fat dairy products and whole-grain bread were promoted and all sweets and sweetened drinks were eliminated in intervention schools . Physical activity ( PA ) was aim ed to increase by 30 min day−1 during school time and sedentary behaviour restricted during after school care time . PA was measured by accelerometry . Eating habits at home were assessed by parental report . Eating disorders were evaluated by self-report . Results : The prevalence of overweight and obesity decreased by 3.2 % ( from 20.3 to 17.1 ) in intervention schools compared with an increase of 2.8 % ( from 16.1 to 18.9 ) in control schools ( P analysis of BMI sds changes . However , a larger proportion of the children who were initially overweight reached normal weight in the intervention group ( 14 % ) compared with the control group ( 7.5 % ) , P=0.017 . PA did not differ between intervention and control schools after cluster adjustment . Eating habits at home were found to be healthier among families with children in intervention schools at the end of the intervention . There was no difference between children in intervention and control schools in self-reported eating disorders . Conclusions : A school-based intervention can reduce the prevalence of overweight and obesity in 6 to 10-year-old children and may affect eating habits at home . The effect of the intervention was possibly due to its effect on healthy eating habits at school and at home rather than on increased levels of PA ", "CONTEXT Some observational studies have found an association between television viewing and child and adolescent adiposity . OBJECTIVE To assess the effects of reducing television , videotape , and video game use on changes in adiposity , physical activity , and dietary intake . DESIGN R and omized controlled school-based trial conducted from September 1996 to April 1997 . SETTING Two sociodemographically and scholastically matched public elementary schools in San Jose , Calif. PARTICIPANTS Of 198 third- and fourth- grade students , who were given parental consent to participate , 192 students ( mean age , 8.9 years ) completed the study . INTERVENTION Children in 1 elementary school received an 18-lesson , 6-month classroom curriculum to reduce television , videotape , and video game use . MAIN OUTCOME MEASURES Changes in measures of height , weight , triceps skinfold thickness , waist and hip circumferences , and cardiorespiratory fitness ; self-reported media use , physical activity , and dietary behaviors ; and parental report of child and family behaviors . The primary outcome measure was body mass index , calculated as weight in kilograms divided by the square of height in meters . RESULTS Compared with controls , children in the intervention group had statistically significant relative decreases in body mass index ( intervention vs control change : 18.38 to 18.67 kg/m2 vs 18.10 to 18.81 kg/m2 , respectively ; adjusted difference -0.45 kg/m2 [ 95 % confidence interval [ CI ] , -0.73 to -0.17 ] ; P = .002 ) , triceps skinfold thickness ( intervention vs control change : 14.55 to 15.47 mm vs 13.97 to 16.46 mm , respectively ; adjusted difference , -1.47 mm [ 95 % CI , -2.41 to -0.54 ] ; P=.002 ) , waist circumference ( intervention vs control change : 60.48 to 63.57 cm vs 59.51 to 64.73 cm , respectively ; adjusted difference , -2.30 cm [ 95 % CI , -3.27 to -1.33 ] ; P waist-to-hip ratio ( intervention vs control change : 0.83 to 0.83 vs 0.82 to 0.84 , respectively ; adjusted difference , -0.02 [ 95 % CI , -0.03 to -0.01 ] ; P children 's reported television viewing and meals eaten in front of the television . There were no statistically significant differences between groups for changes in high-fat food intake , moderate-to-vigorous physical activity , and cardiorespiratory fitness . CONCLUSIONS Reducing television , videotape , and video game use may be a promising , population -based approach to prevent childhood obesity", "Media consumption may contribute to childhood obesity . This study developed and evaluated a theory-based , parent-focused intervention to reduce television and other media consumption to prevent and reduce childhood obesity . Families ( n = 202 ) with children ages 6 - 9 were recruited from a large , urban multiethnic population into a r and omized controlled trial ( 101 families into the intervention group and 101 into the control group ) , and were followed for 6 months . The intervention consisted of a 2-hour workshop and six bimonthly newsletters . Behavioral objectives included : ( i ) reduce TV watching ; ( ii ) turn off TV when nobody is watching ; ( iii ) no TV with meals ; ( iv ) no TV in the child 's bedroom ; and ( v ) engage in fun non-media related activities . Parents were 89 % female , 44 % white , 28 % African American , 17 % Latino , and 11 % Asian , mean age 40 years ( s.d . = 7.5 ) ; 72 % were married . Children were 49 % female , mean age 8 years ( s.d . = 0.95 ) . Sixty-five percent of households had three or more TVs and video game players ; 37 % had at least one h and held video game , and 53 % had three or more computers . Average children 's weekday media exposure was 6.1 hours . At 6 months follow-up , the intervention group was less likely to report the TV being on when nobody was watching ( adjusted odds ratio ( AOR ) = 0.23 , P eating snacks while watching TV ( AOR = 0.47 , P have a TV in the child 's bedroom ( AOR = 0.23 , P actual media consumption but these outcomes did not reach statistical significance . Effective strategies to reduce children 's TV viewing were identified", "OBJECTIVES . Television viewing and physical inactivity increase the risk of obesity in youth . Thus , identifying new interventions that increase physical activity and reduce television viewing would be helpful in the prevention and treatment of pediatric obesity . This study evaluated the effects of open-loop feedback plus reinforcement versus open-loop feedback alone on physical activity , targeted sedentary behavior , body composition , and energy intake in youth . METHODS . Thirty overweight or obese 8- to 12-year-old children were r and omly assigned to an intervention ( n = 14 ) or control group ( n = 16 ) . Participants wore accelerometers every day for 8 weeks and attended biweekly meetings to download the activity monitors . For children in the open-loop feedback plus reinforcement ( intervention ) group , accumulating 400 counts of physical activity on pedometers earned 1 hour of television/VCR/DVD time , which was controlled by a Token TV electronic device . Open-loop feedback control subjects wore activity monitors but had free access to targeted sedentary behavior . RESULTS . Compared with controls , the open-loop feedback plus reinforcement group demonstrated significantly greater increases in daily physical activity counts ( + 65 % vs + 16 % ) and minutes per day of moderate-to-vigorous physical activity ( + 9.4 vs + 0.3 ) and greater reductions in minutes per day spent in television viewing ( −116.1 vs + 14.3 ) . The intervention group also showed more favorable changes in body composition , dietary fat intake , and energy intake from snacks compared with controls . Reductions in sedentary behavior were directly related to reductions in BMI , fat intake , snack intake , and snack intake while watching television . CONCLUSIONS . Providing feedback of physical activity in combination with reinforcing physical activity with sedentary behavior is a simple method of modifying the home environment that may play an important role in treating and preventing child obesity", "Objectives To assess the behavioural and weight status outcomes in English children in a feasibility study of a novel primary school-based obesity prevention programme . Design Exploratory cluster r and omised controlled trial of the Healthy Lifestyles Programme . Setting Four city primary schools ( two control and two intervention ) in the South West of Engl and . Participants 202 children aged 9–10 years , of whom 193 and 188 were followed up at 18 and 24 months , respectively . No child was excluded from the study ; however , to be eligible , schools were required to have at least one single Year 5 class . Intervention Four-phase multicomponent programme using a range of school-based activities including lessons , assemblies , parents ' evenings , interactive drama workshops and goal setting to engage and support schools , children and their families in healthy lifestyle behaviours . It runs over the spring and summer term of Year 5 and the autumn term of Year 6 . Primary and secondary outcomes Weight status outcomes were body mass index , waist circumference and body fat st and ard deviation scores ( SDS ) at 18 and 24 months , and behavioural outcomes were physical activity , television ( TV ) viewing/screen time and food intake at 18 months . Results At 18 months of follow-up , intervention children consumed less energy-dense snacks and more healthy snacks ; had less ‘ negative food markers ’ , more ‘ positive food markers ’ , lower mean TV/screen time and spent more time doing moderate-vigorous physical activity each day than those in the control schools . Intervention children had lower anthropometric measures at 18 and 24 months than control children , with larger differences at 24 months than at 18 months for nearly all measures . Conclusions Results from this exploratory trial show consistent positive changes in favour of the intervention across all targeted behaviours , which , in turn , appear to affect weight status and body shape . A definitive trial is now justified", "Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544", "BACKGROUND Many patients exhibit multiple chronic disease risk behaviors . Research provides little information about advice that can maximize simultaneous health behavior changes . METHODS To test which combination of diet and activity advice maximizes healthy change , we r and omized 204 adults with elevated saturated fat and low fruit and vegetable intake , high sedentary leisure time , and low physical activity to 1 of 4 treatments : increase fruit/vegetable intake and physical activity , decrease fat and sedentary leisure , decrease fat and increase physical activity , and increase fruit/vegetable intake and decrease sedentary leisure . Treatments provided 3 weeks of remote coaching supported by mobile decision support technology and financial incentives . During treatment , incentives were contingent on using the mobile device to self-monitor and attain behavioral targets ; during follow-up , incentives were contingent only on recording . The outcome was st and ardized , composite improvement on the 4 diet and activity behaviors at the end of treatment and at 5-month follow-up . RESULTS Of the 204 individuals r and omized , 200 ( 98.0 % ) completed follow-up . The increase fruits/vegetables and decrease sedentary leisure treatments improved more than the other 3 treatments ( P daily fruit/vegetable intake increased from 1.2 servings to 5.5 servings , sedentary leisure decreased from 219.2 minutes to 89.3 minutes , and saturated fat decreased from 12.0 % to 9.5 % of calories consumed . Differences between treatment groups were maintained through follow-up . Traditional dieting ( decrease fat and increase physical activity ) improved less than the other 3 treatments ( P Remote coaching supported by mobile technology and financial incentives holds promise to improve diet and activity . Targeting fruits/vegetables and sedentary leisure together maximizes overall adoption and maintenance of multiple healthy behavior changes", "OBJECTIVE : To determine if an intervention for preschool-aged children in primary care is effective in reducing screen time , meals in front of the television , and BMI . METHODS : A r and omized controlled trial was conducted at a primary care pediatric group practice in Toronto , Canada . Three-year-old children and their parents were r and omly assigned to receive a short behavioral counseling intervention on strategies to decrease screen time . The primary outcome 1 year later was parent reported screen time . Secondary outcomes included television in the child ’s bedroom , number of meals in front of the television , and BMI . RESULTS : In the intention-to-treat analysis at 1 year , there were no significant differences in mean total weekday minutes of screen time ( 60 , interquartile range [ IQR ] : 35–120 vs 65 , IQR : 35–120 ; P = .68 ) or mean total weekend day minutes of screen time ( 80 , IQR : 45–130 vs 90 , IQR : 60–120 ; P = .33 ) between the intervention and control group . Adjusting for baseline BMI , there was a reduction in the number of weekday meals in front of the television ( 1.6 ± 1.0 vs 1.9 ± 1.2 ; P = .03 ) but no differences in BMI or number of televisions in the bedroom . CONCLUSIONS : This pragmatic trial was not effective in reducing screen time or BMI but was effective in reducing meals in front of the screen . Short interventions focused solely on reducing screen time implemented in the primary care practice setting may not be effective in this age group", "Background Many children spend too much time screen-viewing ( watching TV , surfing the internet and playing video games ) and do not meet physical activity ( PA ) guidelines . Parents are important influences on children ’s PA and screen-viewing ( SV ) . There is a shortage of parent-focused interventions to change children ’s PA and SV . Methods Teamplay was a two arm individualized r and omized controlled feasibility trial . Participants were parents of 6–8 year old children . Intervention participants were invited to attend an eight week parenting program with each session lasting 2 hours . Children and parents wore an accelerometer for seven days and minutes of moderate-to-vigorous intensity PA ( MVPA ) were derived . Parents were also asked to report the average number of hours per day that both they and the target child spent watching TV . Measures were assessed at baseline ( time 0 ) at the end of the intervention ( week 8) and 2 months after the intervention had ended ( week 16 ) . Results There were 75 participants who provided consent and were r and omized but 27 participants withdrew post-r and omization . Children in the intervention group engaged in 2.6 fewer minutes of weekday MVPA at Time 1 but engaged in 11 more minutes of weekend MVPA . At Time 1 the intervention parents engaged in 9 more minutes of weekday MVPA and 13 more minutes of weekend MVPA . The proportion of children in the intervention group watching ≥ 2 hours per day of TV on weekend days decreased after the intervention ( time 0 = 76 % , time 1 = 39 % , time 2 = 50 % ) , while the control group proportion increased slightly ( 79 % , 86 % and 87 % ) . Parental weekday TV watching decreased in both groups . In post- study interviews many mothers reported problems associated with wearing the accelerometers . In terms of a future full-scale trial , a sample of between 80 and 340 families would be needed to detect a mean difference of 10-minutes of weekend MVPA . Conclusions Teamplay is a promising parenting program in an under- research ed area . The intervention was acceptable to parents , and all elements of the study protocol were successfully completed . Simple changes to the trial protocol could result in more complete data collection and study engagement", "This study evaluated the effectiveness of an open-loop system that reinforces physical activity with TV watching to increase children 's physical activity . Nonoverweight , sedentary boys and girls ( 8 - 12 y ) were r and omized to a group that received feedback of activity counts + reinforcement for physical activity by providing access to television ( F+R , n = 20 ) ; or to feedback , no reinforcement ( Feedback , n = 20 ) or no feedback , no reinforcement control ( Control , n = 21 ) groups . Children wore an accelerometer with a count display for 4-months with a 1-year follow-up . F+R reduced TV by 68 min/day and TV time was lower than the Feedback ( p TV time of F+R remained 31 min lower ( p increase in physical activity , which was greater than the feedback ( p TV viewing and increases physical activity of children for 4-months . TV of the F+R group remained lower at 12 months , suggesting a reduction in screen-time habits", "OBJECTIVE : To assess the effectiveness of a parent-focused intervention on infants ’ obesity-risk behaviors and BMI . METHODS : This cluster r and omized controlled trial recruited 542 parents and their infants ( mean age 3.8 months at baseline ) from 62 first-time parent groups . Parents were offered six 2-hour dietitian-delivered sessions over 15 months focusing on parental knowledge , skills , and social support around infant feeding , diet , physical activity , and television viewing . Control group parents received 6 newsletters on nonobesity-focused themes ; all parents received usual care from child health nurses . The primary outcomes of interest were child diet ( 3 × 24-hour diet recalls ) , child physical activity ( accelerometry ) , and child TV viewing ( parent report ) . Secondary outcomes included BMI z-scores ( measured ) . Data were collected when children were 4 , 9 , and 20 months of age . RESULTS : Unadjusted analyses showed that , compared with controls , intervention group children consumed fewer grams of noncore drinks ( mean difference = –4.45 ; 95 % confidence interval [ CI ] : –7.92 to –0.99 ; P = .01 ) and were less likely to consume any noncore drinks ( odds ratio = 0.48 ; 95 % CI : 0.24 to 0.95 ; P = .034 ) midintervention ( mean age 9 months ) . At intervention conclusion ( mean age 19.8 months ) , intervention group children consumed fewer grams of sweet snacks ( mean difference = –3.69 ; 95 % CI : –6.41 to –0.96 ; P = .008 ) and viewed fewer daily minutes of television ( mean difference = –15.97 : 95 % CI : –25.97 to –5.96 ; P = .002 ) . There was little statistical evidence of differences in fruit , vegetable , savory snack , or water consumption or in BMI z-scores or physical activity . CONCLUSIONS : This intervention result ed in reductions in sweet snack consumption and television viewing in 20-month-old children", "OBJECTIVE To evaluate the impact of a school-based interdisciplinary health behavior intervention on diet and physical activity among children in grade s 4 and 5 . DESIGN A quasiexperimental field trial with 6 intervention and 8 matched control schools . Outcomes were assessed longitudinally using preintervention ( fall 1995 ) and follow-up ( spring 1997 ) student survey food frequency and activity measures and follow-up 24-hour recall measures of diet and activity . Change was also assessed using yearly repeated cross-sectional surveys of all grade 5 students from 1995 through 1997 . PARTICIPANTS Longitudinal data were collected from 479 students initially in grade 4 in Baltimore , Md , public schools ; 91 % were African American . Repeated 24-hour recall measures in 1997 were collected for a r and om sub sample of 336 students . Cross-sectional survey data were collected from all grade 5 students in 1995,1996 , and 1997 ( n = 2103 ) . INTERVENTION The Eat Well and Keep Moving Program was taught by classroom teachers over 2 years in math , science , language arts , and social studies classes . Material s provided links to school food services and families and provided training and wellness programs for teachers and other staff members . Intervention material s focused on decreasing consumption of foods high in total and saturated fat and increasing fruit and vegetable intake , as well as reducing television viewing and increasing physical activity . MAIN OUTCOME MEASURES Dietary intake and physical activity measured via repeated 24-hour recall were primary end points , with additional food frequency and activity measures . RESULTS The 24-hour recall measures indicated that , after controlling for baseline covariates , the percentages of total energy from fat and saturated fat were reduced among students in intervention compared with control schools ( -1.4 % ; 95 % confidence interval [ CI ] , -2.8 to -0.04 ; P = .04 and -0.60 % ; 95 % CI , -1.2 to -0.01 ; P = .05 ) . There was an increase in fruit and vegetable intake ( 0.36 servings/4184 kJ ; 95 % CI , 0.10 - 0.62 ; P=.01 ) , in vitamin C intake ( 8.8 mg/4184 kJ ; 95 % CI , 2.0 - 16 ; P=.01 ) , and in fiber consumption ( 0.7 g/4184 kJ ; 95 % CI , 0.0 - 1.4 ; P=.05 ) . Television viewing was marginally reduced ( -0.55 h/d ; 95 % CI , -1.04 to 0.04 ; P=.06 ) . Analysis of longitudinal and repeated cross-sectional food frequency data indicated similar significant decreases in the percentages of total energy from fat and saturated fat . CONCLUSION Evaluation of the Eat Well and Keep Moving Program indicates effectiveness in improving dietary intake of students and reducing television viewing", "The purpose of the present study was to evaluate an intervention to prevent weight gain among households ( HHs ) in the community . Ninety HHs were r and omized to intervention or control group for 1 year . Intervention consisted of six face-to-face group sessions , placement of a television ( TV ) locking device on all home TVs , and home-based intervention activities . Measures were collected in person at baseline and 1 year . Weight , height , eating behaviors , physical activity ( PA ) , and TV viewing were measured among HH members ages ≥ 12 years . Follow-up rate at 1 year was 96 % . No significant intervention effects were observed for change in HH BMI -z score . Intervention HHs significantly reduced TV viewing , snacks/sweets intake , and dollars per person spent eating out , and increased ( adults only ) PA and self-weighing frequency compared with control HHs . A 1 year obesity prevention intervention targeting entire HHs was effective in reducing TV viewing , snack/sweets intake and eating out purchases . Innovative methods are needed to strengthen the home food environment intervention component . Longer intervention duration s also need to be evaluated", "BACKGROUND The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours , and improve weight status among children . OBJECTIVE Test the feasibility of Helping H AND ( Healthy Activity and Nutrition Directions ) , an obesity intervention for 5- to 8-year-old children in primary care clinics . METHODS A r and omized controlled pilot study of Helping H AND , a 6-month intervention , targeted children with body mass index 85 - 99%tile and their parents . Intervention group attended monthly sessions and self-selected child behaviours and parenting practice s to change . Control group received regular paediatric care and was wait-listed for Helping H AND . Session completion , participant satisfaction , child anthropometrics , dietary intake , physical activity , TV viewing and behaviour-specific parenting practice s were measured pre and post intervention . RESULTS Forty parent-child dyads enrolled : 82.5 % were Hispanic , 80 % had a girl and 65 % reported income ≤ $ 30 , 000/year . There was 20 % attrition from Helping H AND ( attended in the child 's body mass index z-score , dietary intake or physical activity post intervention . Intervention group viewed 14.9 ( SE 2.3 ) h/week of TV post intervention versus control group 23.3 ( SE 2.4 ) h/week ( P CONCLUSION Helping H AND is feasible , due to low attrition , good programme attendance , and clinical ly relevant improvements in some child and parenting behaviours", "Low levels of physical activity coupled with high levels of television viewing have been linked with obesity in children . The objective of this study was to assess the efficacy of ' Switch Off-Get Active ' , a 16-week controlled health education intervention , in increasing physical activity and reducing screen time and BMI in primary school children . A secondary objective was to compare children with high and low screen time . Participants were 312 children aged 10.2+/-0.7 years , attending nine schools in areas of social disadvantage . The 10-lesson , teacher-led intervention , conducted in spring 2003 , emphasised self-monitoring , budgeting of time and selective viewing . Differences , adjusted for baseline values by ANCOVA , existed between intervention and control children at follow-up for self-reported physical activity ( intervention + 0.84 30 min blocks/day , 95%CI 0.11 - 1.57 , p self-efficacy for physical activity ( p self-reported screen time ( intervention--0.41 blocks/day , 95%CI--0.93 - 0.12 , p=0.13 ) or BMI ( p=0.63 ) . Cross-sectional comparisons at baseline indicated lower physical activity , self-efficacy for physical activity and aerobic fitness and a higher BMI in children with high screen time . In conclusion , health education interventions can increase physical activity in primary school children but follow-ups of longer duration may be needed to demonstrate intervention effects on BMI", "OBJECTIVE To assess the effects of reducing television viewing and computer use on children 's body mass index ( BMI ) as a risk factor for the development of overweight in young children . DESIGN R and omized controlled clinical trial . SETTING University children 's hospital . PARTICIPANTS Seventy children aged 4 to 7 years whose BMI was at or above the 75th BMI percentile for age and sex . INTERVENTIONS Children were r and omized to an intervention to reduce their television viewing and computer use by 50 % vs a monitoring control group that did not reduce television viewing or computer use . MAIN OUTCOME MEASURES Age- and sex-st and ardized BMI ( z BMI ) , television viewing , energy intake , and physical activity were monitored every 6 months during 2 years . RESULTS Children r and omized to the intervention group showed greater reductions in targeted sedentary behavior ( P z BMI ( P energy intake ( P z BMI change ( P = .01 ) , with the experimental intervention working better among families of low socioeconomic status . Changes in targeted sedentary behavior mediated changes in z BMI ( P television viewing was related to the change in energy intake ( P physical activity ( P = .37 ) . CONCLUSIONS Reducing television viewing and computer use may have an important role in preventing obesity and in lowering BMI in young children , and these changes may be related more to changes in energy intake than to changes in physical activity", "OBJECTIVE To evaluate the short- and long-term results of FATaintPHAT , a Web-based computer-tailored intervention aim ing to increase physical activity , decrease sedentary behavior , and promote healthy eating to contribute to the prevention of excessive weight gain among adolescents . DESIGN Cluster r and omized trial with an intervention group and a no-intervention control group . SETTING Twenty schools in the Netherl and s. PARTICIPANTS A total of 883 students ( aged 12 - 13 years ) . INTERVENTION The FATaintPHAT ( VETisnietVET in Dutch ) Web-based computer-tailored intervention . OUTCOME MEASURES Self-reported behaviors ( diet , physical activity , sedentary behavior ) and pedometer counts were measured at baseline and at 4-month and 2-year follow-up ; body mass index ( BMI ) , waist circumference , and fitness were measured at baseline and at 2-year follow-up . Descriptive and multilevel regression analyses were conducted among the total study population and among students not meeting behavioral recommendations at baseline ( students at risk ) . RESULTS The complete case analyses showed that FATaintPHAT had no effect on BMI and waist circumference . However , the intervention was associated with lower odds ( 0.54 ) of drinking more than 400 mL of sugar-sweetened beverages per day and with lower snack intake ( β = -0.81 snacks/d ) and higher vegetable intake ( β = 19.3 g/d ) but also with a lower step count ( β = -10 856 steps/wk ) at 4-month follow-up . In addition , among students at risk , FATaintPHAT had a positive effect on fruit consumption ( β = 0.39 g/d ) at 4-month follow-up and on step count ( β = 14 228 steps/wk ) at 2-year follow-up but an inverse effect on the odds of sports participation ( odds ratio , 0.45 ) at 4-month follow-up . No effects were found for sedentary behavior . CONCLUSION The FATaintPHAT intervention was associated with positive short-term effects on diet but with no effects or unfavorable effects on physical activity and sedentary behavior", "Translational or implementation research that assesses the effectiveness of strategies to promote health behaviours among children that have been previously tested under ' ideal ' conditions is rarely reported . Switch-2-Activity aim ed to examine the effectiveness of an abbreviated programme delivered by teachers targeting children 's television viewing , computer use , physical activity and potential mediators of behaviour change . Fifteen schools from disadvantaged areas in Melbourne , Australia agreed to participate in the study ( 43 % school-level response rate ) . Out of the 1566 Grade s 5 and 6 ( 9 - 12 year old ) children invited to take part in the study , 1048 ( 67 % response rate ) provided informed consent . Schools were r and omized to either an intervention or wait-list control condition . Teachers delivered six lessons , which included strategies such as self-monitoring , behavioural contracting and budgeting of screen time . Children completed a self-report survey at baseline and post-intervention examining screen-based behaviours , physical activity , self-efficacy and behavioural capability . Teachers reported implementation of and attitudes to the programme . Seventy-one per cent of teachers delivered at least four of the six lessons . Most teachers reported that the material s were easy to follow and deliver ; however , many teachers reported modifying the material s in some way . Among boys , there were favourable small intervention effects on weekend screen time [ ( coefficient = -0.62 , 95 % 95 % confidence interval : -1.15 , -0.10 , p = 0.020 ) ] . The intervention also had significant positive effects on children 's self-efficacy for reducing television viewing and on behavioural capability ( television viewing styles ) . Future studies that assess the translation of efficacious programmes and that test whether such programmes are equally effective in different setting s ( e.g. in the family setting ) are urgently required", "BACKGROUND Data are lacking on primary care interventions to reduce children 's television viewing . Low-income African-American children watch greater amounts of television than their peers . DESIGN / METHODS A r and omized controlled pilot and feasibility trial was conducted . Twenty-eight families with 7- to 12-year-old African-American children receiving primary care at an urban community clinic serving a low-income population were r and omized to receive counseling alone or counseling plus a behavioral intervention that included an electronic television time manager . The main outcome was hours of children 's television , videotape , and video game use . Parents/guardians and children completed baseline and 4-week follow-up self-report surveys . Additional outcomes included overall household television use , time spent in organized physical activity and playing outside , and meals eaten by the child while watching television . RESULTS Both intervention groups reported similar decreases in children 's television , videotape , and video game use ( mean changes of -13.7 , SD=26.1 and -14.1 , SD=16.8 hours per week ) . The behavioral intervention group reported significantly greater increases in organized physical activity ( changes of + 2.5 , SD=5.9 and -3.6 , SD=4.7 hours per week ; p = 0.004 ) and nearly significant greater increases in playing outside ( changes of 1.0 , SD=5.9 and -4.7 , SD=9.4 hours per week ; p overall household television use and meals eaten while watching television also appeared to favor the behavioral intervention , with small to medium effect sizes , but differences were not statistically significant . CONCLUSIONS This small pilot and feasibility study evaluated two promising primary care-based interventions to reduce television , videotape , and video game use among low-income African-American children . The effects on physical activity suggest that the behavioral intervention may be more effective", "This paper describes the development , implementation and evaluation of a school- and family-based intervention to prevent obesity in children aged 5 - 7 years . In addition , the efficacy of three different intervention programmes was compared . Children aged 5 - 7 years ( n=213 ) were recruited from three primary schools in Oxford and r and omly allocated to a control group or one of three intervention groups : nutrition group , physical activity group , and combined nutrition and physical activity group . The setting for the interventions was lunchtime clubs , where an interactive and age-appropriate nutrition and /or physical activity curriculum was delivered . The intervention lasted for 20 weeks over four school terms ( approximately 14 months ) . Children 's growth , nutrition knowledge , diet and physical activity were assessed at baseline and at the end of the intervention . Significant improvements in nutrition knowledge were seen in all children ( p fruit and vegetable intake increased significantly ( p rates of overweight and obesity were seen as a result of the intervention . Gender differences were not detected in the majority of assessment s and there was no clear effect of programme type per se . This pilot study has demonstrated that school may be a suitable setting for the promotion of healthy lifestyles in children , but requires replication in other social setting s. Future initiatives should be long-lasting , multi-faceted and sustainable , involving all children in a school , and should target the whole environment and be behaviourally focused . The ultimate goal of any such programme is to lead to positive behaviour change which will have a beneficial effect on long-term health . Successful targeting of the family remains a challenge to such interventions", "PURPOSE The number of youth that meet activity guidelines is decreasing and easy access to reinforcing sedentary behaviors competes with increasing physical activity . In the laboratory , open-loop feedback that used pedometer activity counts to gain access to sedentary alternatives doubled physical activity . This study evaluated the influence of open-loop feedback and reinforcement on physical activity and television ( TV ) time in a small clinical trial . METHODS Children ( 8 - 12 yr old ) were r and omized to an open-loop feedback plus reinforcement intervention ( N = 11 ) or no feedback , no reinforcement control ( N = 7 ) . Subjects wore an accelerometer for 6 wk and attended meetings to download the accelerometer . Accumulating physical activity counts gave subjects in the open-loop group access to TV time , controlled by a TV Allowance device , with 400 counts = 1 h of TV . The control group had no feedback for activity and free access to TV . RESULTS The open-loop group had a 24 % increase in physical activity , which was greater ( P = 0.02 ) than the control group . TV time of the open-loop group was reduced by 18 % or 20 min x d(-1 ) whereas the control group increased by 13 min x d(-1 ) , but these were not significant changes . The change in time spent watching television was directly related to the change in BMI z-score ( r = 0.69 , P = 0.002 ) . CONCLUSION Open-loop feedback increases physical activity in children , thus helping children to achieve physical activity recommendations . Reductions in TV watching may reduce or minimize gains in body weight", "OBJECTIVE To evaluate the impact of a Special Supplemental Nutrition Program for Women , Infants , and Children (WIC)-based intervention on the food and beverage intake , physical activity , and television watching of children ages 1 - 5 . DESIGN Longitudinal surveys of intervention and control participants at baseline , 6 months , and 12 months . RESULTS Analysis of variance tests showed that the intervention had a small but significant impact on TV watching and fruit intake . The intervention was most protective for children younger than 2 years of age . CONCLUSIONS AND IMPLICATION S Although the impact of the intervention was relatively small and limited to the youngest children served by WIC , findings suggest that the WIC setting is appropriate for improving healthful behaviors that are linked to reducing the rates of early childhood overweight ", " Obese children 8 - 12 years old from 61 families were r and omized to treatment groups that targeted increased exercise , decreased sedentary behaviors , or both ( combined group ) to test the influence of reinforcing children to be more active or less sedentary on child weight change . Significant decreases in percentage overweight were observed after 4 months between the sedentary and the exercise groups ( -19.9 vs. -13.2 ) . At 1 year , the sedentary group had a greater decrease in percentage overweight than did the combined and the exercise groups ( -18.7 vs. -10.3 and -8.7 ) and greater decrease in percentage of body fat ( -4.7 vs. -1.3 ) . All groups improved fitness during treatment and follow-up . Children in the sedentary group increased their liking for high-intensity activity and reported lower caloric intake than did children in the exercise group . These results support the goal of reducing time spent in sedentary activities to improve weight loss", "BACKGROUND Television viewing has been associated with increased violence in play and higher rates of obesity . Although there are interventions to reduce television viewing by school-aged children , there are none for younger children . OBJECTIVE To develop and evaluate an intervention to reduce television viewing by preschool children . DESIGN R and omized controlled trial conducted in 16 preschool and /or day care centers in rural upstate New York . PATIENTS Children aged 2.6 through 5.5 years . INTERVENTION Children attending intervention centers received a 7-session program design ed to reduce television viewing as part of a health promotion curriculum , whereas children attending the control centers received a safety and injury prevention program . OUTCOME MEASUREMENTS Change in parent-reported child television/video viewing and measured growth variables . RESULTS Before the intervention , the intervention and control groups viewed 11.9 and 14.0 h/wk of television/videos , respectively . Afterward , children in the intervention group decreased their television/video viewing 3.1 h/wk , whereas children in the control group increased their viewing by 1.6 h/wk , for an adjusted difference between the groups of -4.7 h/wk ( 95 % confidence interval , -8.4 to -1.0 h/wk ; P = .02 ) . The percentage of children watching television/videos more than 2 h/d also decreased significantly from 33 % to 18 % among the intervention group , compared with an increase of 41 % to 47 % among the control group , for a difference of -21.5 % ( 95 % confidence interval , -42.5 % to -0.5 % ; P = .046 ) . There were no statistically significant differences in children 's growth between groups . CONCLUSIONS This study is the first to show that a preschool-based intervention can lead to reductions in young children 's television/video viewing . Further research is needed to determine the long-term effects associated with reductions in young children 's television viewing", "OBJECTIVES This pilot study evaluated the feasibility ( recruitment , retention , and acceptability ) and preliminary efficacy of a six-week home-based electronic time monitor intervention on New Zeal and children 's television watching in 2008 . METHODS Twenty-nine children aged 9 to 12 years who watched more than 20 h of television per week ( 62 % male , mean age 10.4 years ) were r and omised to either the intervention or the control group . The intervention group received an electronic TV time monitor for 6 weeks and advice to restrict TV watching to 1 h per day or less . The control group was given verbal advice to restrict TV watching . RESULTS Participant retention at 6 weeks was 93 % . Semi-structured interviews with intervention families confirmed moderate acceptability of TV time monitors and several perceived benefits including better awareness of household TV viewing and improved time planning . Drawbacks reported included disruption to parents ' TV watching and increased sibling conflict . Time spent watching television decreased by 4.2 h ( mean change [ SD ] : -254 [ 536 ] min ) per week in the intervention group compared with no change in the control group ( -3 [ 241 ] min ) , but the difference between groups was not statistically significant , p=0.77 . Both groups reported decreases in energy intake from snacks and total screen time and increases in physical activity measured by pedometer and between-group differences were not statistically significant . CONCLUSIONS Electronic TV time monitors are feasible to use for home-based TV watching interventions although acceptability varies between families . Preliminary findings from this pilot suggest that such devices have potential to decrease children 's TV watching but a larger trial is needed to confirm effectiveness . Future research should be family-orientated ; take account of other screen time activities ; and employ TV time monitors as just one of a range of strategies to decrease sedentary behaviour", "OBJECTIVE Many adolescents do not meet national guidelines for participation in regular moderate or vigorous physical activity ( PA ) ; limitations on sedentary behaviors ; or dietary intake of fruits and vegetables , fiber , or total dietary fat . This study evaluated a health care-based intervention to improve these behaviors . DESIGN R and omized controlled trial . SETTING Primary care with follow-up at home . PARTICIPANTS Eight hundred seventy-eight adolescent girls and boys aged 11 to 15 years . INTERVENTIONS Two experimental conditions : ( 1 ) Primary care , office-based , computer-assisted diet and PA assessment and stage-based goal setting followed by brief health care provider counseling and 12 months of monthly mail and telephone counseling and ( 2 ) a comparison condition addressing sun exposure protection . MAIN OUTCOME MEASURES Minutes per week of moderate plus vigorous PA measured by self-report and accelerometer ; self-report of days per week of PA and sedentary behaviors ; and percentage of energy from fat and servings per day of fruits and vegetables measured by three 24-hour diet recalls . Body mass index ( calculated as weight in kilograms divided by the square of height in meters ) was a secondary outcome . RESULTS Compared with adolescents in the sun protection condition , girls and boys in the diet and PA intervention significantly reduced sedentary behaviors ( intervention vs control change , 4.3 to 3.4 h/d vs 4.2 to 4.4 h/d for girls , respectively [ P = .001 ] ; 4.2 to 3.2 h/d vs 4.2 to 4.3 h/d for boys , respectively [ P = .001 ] ) . Boys reported more active days per week ( intervention vs control change : 4.1 to 4.4 d/wk vs 3.8 to 3.8 d/w , respectively [ P = .01 ] ) , and the number of servings of fruits and vegetables for girls approached significance ( intervention vs control change , 3.5 to 4.2 servings/d vs 3.5 to 3.9 servings/d , respectively [ P = .07 ] ) . No intervention effects were seen with percentage of calories from fat or minutes of PA per week . Percentage of adolescents meeting recommended health guidelines was significantly improved for girls for consumption of saturated fat ( intervention vs control change , 23.4 % to 41.0 % vs 18.5 % to 31 % , respectively [ relative risk , 1.33 ; 95 % confidence interval , 1.01 - 1.68 ] ) and for boys ' participation in d/wk of PA ( intervention vs control change , 45.3 % to 55.4 % vs 41.9 % to 38.0 % , respectively [ relative risk , 1.47 ; 95 % confidence interval , 1.19 - 1.75 ] ) . No between-group differences were seen in body mass index . CONCLUSIONS Improvements in some diet , PA , and sedentary behaviors in adolescents can be enabled through the use of a 1-year , integrated intervention using the computer , health provider counseling , mail , and telephone . The amount of intervention received may contribute to its efficacy", "BACKGROUND The average adult watches almost 5 hours of television ( TV ) per day , an amount associated with increased risks for obesity . This trial examines the effects of TV reduction on energy intake ( EI ) , energy expenditure ( EE ) , energy balance , body mass index ( BMI ) , ( calculated as weight in kilograms divided by height in meters squared ) , and sleep in overweight and obese adults . METHODS R and omized controlled trial of 36 adults with a BMI of 25 to 50 who self-reported a minimum of 3 h/d of TV viewing . Participants were enrolled in home-based protocol s from January through July 2008 . After a 3-week observation phase , participants were stratified by BMI and r and omized to an observation-only control group ( n = 16 ) or an intervention group ( n = 20 ) for 3 additional weeks . The intervention consisted of reducing TV viewing by 50 % of each participant 's objective ly measured baseline enforced by an electronic lock-out system . RESULTS Although not statistically significant , both groups reduced their EI ( -125 kcal/d [ 95 % CI , -303 to 52 ] vs -38 [ 95 % CI , -265 to 190 ] ) ( P = .52 ) for intervention and control group participants , respectively , where CI indicates confidence interval . The intervention group significantly increased EE ( 119 kcal/d [ 95 % CI , 23 to 215 ] ) compared with controls ( -95 kcal/d [ 95 % CI , -254 to 65 ] ) ( P = .02 ) . Energy balance was negative in the intervention group between phases ( -244 kcal/d [ 95 % CI , -459 to -30 ] ) but positive in controls ( 57 kcal/d [ 95 % CI , -216 to 330 ] ) ( P = .07 ) . The intervention group showed a greater reduction in BMI ( -0.25 [ 95 % CI , -0.45 to -0.05 ] vs -0.06 [ 95 % CI , -0.43 to 0.31 ] in controls ) ( P = .33 ) . There was no change in sleep . CONCLUSION Reducing TV viewing in our sample produced a statistically significant increase in EE but no apparent change in EI after 3 weeks of intervention . Trial Registration clinical trials.gov Identifier : NCT00622050", "Objectives : To evaluate the effectiveness of an intervention to prevent excess weight gain , reduce time spent in screen behaviours , promote participation in and enjoyment of physical activity ( PA ) , and improve fundamental movement skills among children . Participants : In 2002 , 311 children ( 78 % response ; 49 % boys ) , average age 10 years 8 months , were recruited from three government schools in low socioeconomic areas of Melbourne , Australia . Design : Group-r and omized controlled trial . Children were r and omized by class to one of the four conditions : a behavioural modification group ( BM ; n=66 ) ; a fundamental movement skills group ( FMS ; n=74 ) ; a combined BM/FMS group ( BM/FMS ; n=93 ) ; and a control ( usual curriculum ) group ( n=62 ) . Data were collected at baseline , post intervention , 6- and 12-month follow-up periods . Results : BMI data were available for 295 children at baseline and 268 at 12-month follow-up . After adjusting for food intake and PA , there was a significant intervention effect from baseline to post intervention on age- and sex-adjusted BMI in the BM/FMS group compared with controls ( −1.88 kg m−2 , P overweight/obese between baseline and post intervention ( adjusted odds ratio (AOR)=0.36 , P recorded higher levels and greater enjoyment of PA ; and BM children recorded higher levels of PA and TV viewing across all four time points . Gender moderated the intervention effects for participation in and enjoyment of PA , and fundamental movement skills . Conclusion : This programme represents a promising approach to preventing excess weight gain and promoting participation in and enjoyment of PA . Examination of the mediators of this intervention and further tailoring of the programme to suit both genders is required", "OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year ( 6 intervention contacts ) of a planned 2-year study . DESIGN Cluster r and omized controlled trial . SETTING Ten pediatric practice s , 5 intervention and 5 usual care . PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index ( BMI ) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight ; 445 ( 93 % ) had 1-year outcomes . INTERVENTION Intervention practice s received primary care restructuring , and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake . OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year . RESULTS Compared with usual care , intervention participants had a smaller , nonsignificant change in BMI ( -0.21 ; 95 % confidence interval [ CI ] , -0.50 to 0.07 ; P = .15 ) , greater decreases in television viewing ( -0.36 h/d ; 95 % CI , -0.64 to -0.09 ; P = .01 ) , and slightly greater decreases in fast food ( -0.16 serving/wk ; 95 % CI , -0.33 to 0.01 ; P = .07 ) and sugar-sweetened beverage ( -0.22 serving/d ; 95 % CI , -0.52 to 0.08 ; P = .15 ) intake . In post hoc analyses , we observed significant effects on BMI among girls ( -0.38 ; 95 % CI , -0.73 to -0.03 ; P = .03 ) but not boys ( 0.04 ; 95 % CI , -0.55 to 0.63 ; P = .89 ) and among participants in households with annual incomes of $ 50 000 or less ( -0.93 ; 95 % CI , -1.60 to -0.25 ; P = .01 ) but not in higher-income households ( 0.02 ; 95 % CI , -0.30 to 0.33 ; P = .92 ) . CONCLUSION After 1 year , the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI", "Objective : Given the increasing prevalence of pediatric obesity , we evaluated two kindergarten-based strategies for reducing overweight in preschool children in the Haute-Garonne Department in France . Methods : Kindergartens ( n=79 ) were r and omly assigned to one of the two strategies and followed for 2 years . In the first group ( Epidémiologie et prévention de l’obésité infantile , EPIPOI-1 ) , parents and teachers received basic information on overweight and health , and children underwent screening to identify those with overweight ( body mass index ( BMI ) ⩾90th percentile ) or at risk for overweight ( BMI between 75 and 90th percentile ) , who were then followed up by their physicians . EPIPOI-2 children , in addition , received kindergarten-based education to promote healthy practice s related to nutrition , physical activity and sedentary behaviors . Data on control children from non-intervention kindergartens ( n=40 ) were retrieved from medical records at the Division of School Health . Results : At baseline , groups differed significantly on age and school area ( underprivileged/ not ) . Owing to a significant interaction between school area and group , analyses were stratified by school area . At baseline , groups did not differ on overweight prevalence and BMI z-scores for any school area . After intervention , prevalence of overweight , BMI z-score and change in BMI z-score were significantly lower in intervention groups compared with controls in underprivileged areas . Using multilevel analysis adjusted for potential confounders , a significant effect on overweight prevalence at the end of the study was noted for EPIPOI-1 in underprivileged areas only ( odds ratio and 95 % confidence interval : 0.18 ( 0.07–0.51 ) . In non-underprivileged areas , the gain in BMI z-score was lower in EPIPOI-2 group compared with control and EPIPOI-1 . Conclusion : Our results suggest that simple measures involving increasing awareness on overweight and health , and periodic monitoring of weight and height with follow-up care when indicated , could be useful to reduce overweight in young children from underprivileged areas . A reinforced strategy with an education component , in addition , may be indicated in children in non-underprivileged areas", "OBJECTIVE To examine acceptability , attrition , adherence , and preliminary efficacy of mobile phone short message service ( SMS ; text messaging ) for monitoring healthful behaviors in children . DESIGN All r and omized children received a brief psychoeducational intervention . They then either monitored target behaviors via SMS with feedback or via paper diaries ( PD ) or participated in a no-monitoring control ( C ) for 8 weeks . SETTING University of North Carolina at Chapel Hill . PARTICIPANTS Fifty-eight children ( age 5 - 13 ) and parents participated ; 31 completed ( SMS : 13/18 , PD : 7/18 , C : 11/22 ) . INTERVENTION Children and parents participated in a total of 3 group education sessions ( 1 session weekly for 3 weeks ) to encourage increasing physical activity and decreasing screen time and sugar-sweetened beverage consumption . MAIN OUTCOME MEASURES Treatment acceptability , attrition , and adherence to self-monitoring . ANALYSIS Descriptive statistics and nonparametric tests were used to analyze differences across time and group . RESULTS Children in SMS had somewhat lower attrition ( 28 % ) than both PD ( 61 % ) and C ( 50 % ) , and significantly greater adherence to self-monitoring than PD ( 43 % vs 19 % , P self-monitoring healthful behaviors in children , although the efficacy of this approach needs further study . Implication s suggest that novel technologies may play a role in improving health" ]

[ "In this initial pilot study , a controlled clinical comparison was made of attention perforance in children with attention deficit-hyperactivity disorder ( ADHD ) in a virtual reality ( VR ) classroom . Ten boys diagnosed with ADHD and ten normal control boys participated in the study . Groups did not significantly differ in mean age , grade level , ethnicity , or h and edness . No participants reported simulator sickness following VR exposure . Children with ADHD exhibited more omission errors , commission errors , and overall body movement than normal control children in the VR classroom . Children with ADHD were more impacted by distraction in the VR classroom . VR classroom measures were correlated with traditional ADHD assessment tools and the flatscreen CPT . Of note , the small sample size incorporated in each group and higher WISC-III scores of normal controls might have some bearing on the overall interpretation of results . These data suggested that the Virtual Classroom had good potential for controlled performance assessment within an ecologically valid environment and appeared to parse out significant effects due to the presence of distraction stimuli", "Primary objective : There is controversy surrounding the cognitive effects of sports concussion . This study aim ed to verify whether the technique of virtual reality could aid in the identification of attention and inhibition deficits in adolescents . Study design : A prospect i ve design was used to assess 25 sports-concussed and 25 non-sports-concussed adolescents enrolled in a sport and education programme . Methods and procedures : Participants were evaluated in immersive virtual reality via ClinicaVR : Classroom-CPT and in real life via the traditional VIGIL-CPT . Main outcomes and results : The neuropsychological assessment using virtual reality showed greater sensitivity to the subtle effects of sports concussion compared to the traditional test , which showed no difference between groups . The results also demonstrated that the sports concussion group reported more symptoms of cybersickness and more intense cybersickness than the control group . Conclusions : Sports concussion was associated with subtle deficits in attention and inhibition . However , further studies are needed to support these results", "The objectives of this study were to describe the nature of the attention deficits in children with Neurofibromatosis type 1 ( NF1 ) in comparison with typically developing ( TD ) children , using the Virtual Classroom ( VC ) , and to assess the utility of this instrument for detecting attention deficits . Twenty-nine NF1 children and 25 age- and gender-matched controls , aged 8 - 16 , were assessed in a VC . Parents ' ratings on the Conners ' Parent Rating Scales-Revised : Long ( CPRS-R : L ) question naire were used to screen for Attention Deficit-Hyperactivity Disorder ( ADHD ) . Significant differences were found between the NF1 and the control groups on the number of targets correctly identified ( omission errors ) and the number of commissions ( commission errors ) in the VC , with poorer performance by the NF1 children ( p number of targets correctly identified , the number of commission errors , and the reaction time . Significant correlations were also found between the total correct hits and the cognitive problems/inattention scale , as well as two other indexes of the CPRS-R : L : the DSM-IV Symptoms Subscale and the ADHD Index . The VC results support the hypothesis that NF1 is marked by inattention and impulsivity and that participants with NF1 are more inattentive ( omission errors ) and impulsive ( commission errors ) than normal controls . The VC appears to be a sensitive and ecologically valid assessment tool for use in the diagnosis of attention deficits among children with NF1", "Objective : The present study describes the obtention of normative data for the AULA test , a virtual reality tool design ed to evaluate attention problems , especially in children and adolescents . Method : The normative sample comprised 1,272 participants ( 48.2 % female ) with an age range from 6 to 16 years ( M = 10.25 , SD = 2.83 ) . The AULA test administered to them shows both visual and auditory stimuli , while r and omized distractors of ecological nature appear progressively . Results : Variables provided by AULA were clustered in different categories for their posterior analysis . Differences by age and gender were analyzed , result ing in 14 groups , 7 per sex group . Differences between visual and auditory attention were also obtained . Conclusion : Obtained normative data are relevant for the use of AULA for evaluating attention in Spanish children and adolescents in a more ecological way . Further studies will be needed to determine sensitivity and specificity of AULA to measure attention in different clinical population s. ( J. of Att . Dis . 2016 ; 20(6 ) 542 - 568" ]

[ " Eighty-seven morbidly obese patients were prospect ively r and omized to two operations : gastric bypass was performed on 42 and gastric partition on 45 . Gastric bypass proved to be more effective ; gastric bypass patients lost 15 % more of their original weight at 12 months and 21 % more at 18 months . There were no failures in the gastric bypass group ; 28 of the 45 operations failed in the gastric partition group . An additional 60 patients underwent gastric bypass since the completion of the study . In the total series of 147 patients who underwent gastric bypass or gastric partition , there was no mortality , and the surgical complication rate was 12 % . Because the gastric pouches and the anastomoses were similar in the two operations , the superiority of the gastric bypass may well be due to a heretofore unexplained effect of distal gastric and duodenal exclusion", " The present status of 38 patients comprising a clinical trial of jejunoileal and gastric bypass for the treatment of morbid obesity , begun four years ago at North Carolina Memorial Hospital , is reported . Weight loss was greater in patients treated by jejunoileal bypass than those treated by gastric bypass . The poorer weight loss noted in the gastric bypass patients is associated with an excessively large proximal gastric pouch , which had characterized the 19 gastric bypass operations done prior to May 1977 . The weight loss achieved with the current version of the gastric bypass , a smaller proximal gastric pouch , is comparable to that achieved with jejunoileal bypass . The objective and subjective sequelae and complications of jejunoileal bypass are more common and more serious than those of gastric bypass . Gastric bypass is the better operation for the treatment of morbid obesity", "Background : Laparoscopic adjustable gastric b and ing ( LAGB ) and open vertical b and ed gastroplasty ( VBG ) are treatment modalities for morbid obesity . However , few prospect i ve r and omized clinical trials ( RCT ) have been performed to compare both operations . Methods : 100 patients ( 50 per group ) were included in the study . Postoperative outcomes included hospital length of stay ( LOS ) , complications , percent excess weight loss ( % EWL ) , BMI and reduction in total comorbidities . Follow-up in all patients was 2 years . Results : LOS was significantly shorter in the LAGB group . 3 LAGB were converted to open ( 1 to gastric bypass ) . Directly after VBG , 3 patients needed relaparotomies due to leakage , of which one ( 2 % ) died . After 2 years , 100 % follow-up was achieved . BMI and % EWL were significantly decreased in both groups but significantly more in the VBG group compared to the LAGB group ( 31.0 kg/m2 and 70.1 % vs 34.6 and 54.9 % respectively ) . Co-morbidities significantly decreased in both groups in time . 2 years after LAGB , 20 patients needed reoperation for pouch dilation/slippage ( n=12 ) , b and leakage ( n=2 ) , b and erosion ( n=2 ) and access-port problems ( n=4 ) . In the VBG group , 18 patients needed revisional surgery due to staple-line disruption ( n=15 ) , narrow outlet ( n=2 ) or insufficient weight loss ( n=1 ) . Furthermore , 8 VBG patients developed an incisional hernia . Conclusion : This RCT demonstrates that , despite the initial better weight loss in the VBG group , based on complication rates and clinical outcome , LAGB is preferred . It had a shorter LOS and less postoperative morbidity", "A prospect i ve r and omized clinical trial was undertaken to compare the effects of gastric bypass with Roux-en-Y gastro-jejunostomy and a gastric partitioning procedure . Operative groups were comparable , with regard to preoperative weight , age , sex , historic findings and operative complications . Postoperative weight loss was followed for one year . Patients receiving the gastric partitioning procedure showed significantly poorer weight loss as early as three months postoperatively than did those receiving gastric bypass . This poorer performance persisted throughout the study period", "Background : Bariatric surgery is currently the most effective treatment in morbidly obese patients , leading to durable weight loss . Objective : In this prospect i ve double blind study , we aim to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) with laparoscopic sleeve gastrectomy ( LSG ) on body weight , appetite , fasting , and postpr and ial ghrelin and peptide-YY ( PYY ) levels . Methods : After r and omization , 16 patients were assigned to LRYGBP and 16 patients to LSG . Patients were reevaluated on the 1st , 3rd , 6th , and 12th postoperative month . Blood sample s were collected after an overnight fast and in 6 patients in each group after a st and ard 420 kcal mixed meal . Results : Body weight and body mass index ( BMI ) decreased markedly ( P Excess weight loss was greater after LSG at 6 months ( 55.5 % ± 7.6 % vs. 50.2 % ± 6.5 % , P = 0.04 ) and 12 months ( 69.7 % ± 14.6 % vs. 60.5 % ± 10.7 % , [ P = 0.05 ] ) . After LRYGBP fasting ghrelin levels did not change significantly compared with baseline ( P = 0.19 ) and did not decrease significantly after the test meal . On the other h and , LSG was followed by a marked reduction in fasting ghrelin levels ( P . Fasting PYY levels increased after either surgical procedure ( P ≤ 0.001 ) . Appetite decreased in both groups but to a greater extend after LSG . Conclusion : PYY levels increased similarly after either procedure . The markedly reduced ghrelin levels in addition to increased PYY levels after LSG , are associated with greater appetite suppression and excess weight loss compared with LRYGBP", "Context Observational studies have shown sustained weight loss after surgery for extreme obesity . No r and omized trial of contemporary surgical methods has been performed . Contribution The authors r and omly assigned 80 mildly to moderately obese ( body mass index , 30 to 35 kg/m2 ) adults to laparoscopic placement of an adjustable gastric b and or to an intensive nonsurgical weight loss program . After 2 years , the surgical group had lost 21.6 % of initial weight , and the nonsurgical group had lost 5.5 % of initial weight . Four patients required laparoscopic revision of the gastric b and . Caution s The study was not design ed to detect uncommon adverse events . Implication s Laparoscopic gastric b and ing is effective treatment for mild to moderate obesity . The Editors The development of a safe and effective treatment for obesity is a leading challenge in health care today . Obesity is an increasing health problem across the world with a prevalence of more than 20 % among the adult population in Western countries and more than 30 % in the United States ( 1 , 2 ) . The increasing prevalence is associated with a parallel increase of several obesity-related diseases , in particular , the diseases of the metabolic syndrome ( 3 , 4 ) , which include type 2 diabetes , hypertension , and dyslipidemia , and are linked to nonalcoholic steatohepatitis , obstructive sleep apnea , and the polycystic ovary syndrome . For obese individuals , the options are limited . Behavioral therapies of reduced energy intake , improved eating practice s , and increased exercise and activity , supplemented by pharmacotherapy , generally achieve only modest and often transient effects ( 5 , 6 ) . Observational studies have shown that bariatric surgical therapies involving gastric restriction by various forms of stapling with or without diversion of the gut to generate malabsorption of food are effective in achieving major weight loss and clinical ly significant improvements in health and quality of life ( 7 - 11 ) . Strong direct evidence from r and omized , controlled trials of the relative benefits of nonsurgical and surgical therapies is lacking . We are aware of only a single study , performed in the 1980s , in which 60 morbidly obese patients were r and omly assigned , without informed consent , to diet plus an early form of gastric stapling or to diet alone ( 12 ) . The maximum weight losses did not differ between the groups . However , the weight regain was greater in the diet-only group . The advent of the laparoscopic adjustable gastric b and has provided a new bariatric surgical option , which has proved to be safe , minimally invasive in its application , gentle in its use through its adjustability and easy reversibility , and similarly effective to the other bariatric procedures ( 10 , 13 , 14 ) . Figure 1 shows the LAP-B AND System ( INAMED Health , Santa Barbara , California ) and demonstrates the key feature of adjustability of the area within the b and through which it induces satiety ( 15 ) . Patients require no more than an overnight hospital stay , and the procedure has been shown to be markedly safer than gastric bypass surgery ( 13 ) . Figure 1 . The laparoscopic adjustable gastric b and ( LAP-B AND System , INAMED Health , Santa Barbara , California ) with no added fluid ( top ) and with 2 mL of fluid added ( bottom ) . We hypothesized that surgical therapy would induce more weight loss , health benefit , and improvement in quality of life than nonsurgical therapy and have conducted a r and omized , controlled trial comparing the effectiveness of current nonsurgical therapy with laparoscopic adjustable gastric b and ing in a group of mildly to moderately obese adults ( body mass index , 30 kg/m2 to 35 kg/m2 ) . We did not study patients with a body mass index greater than 35 kg/m2 because current observational data suggest that outcomes after nonsurgical treatment were unlikely to be equal to those after surgical care for these patients . The principal outcome measures were weight change , health , quality of life , and complications of therapy . Methods Patient Recruitment We recruited patients for the study through a newspaper advertisement . All patient assessment s and outpatient treatments were conducted at a community clinic dedicated to obesity management or in the clinics of a university department of surgery . Surgical procedures were conducted at a private community hospital experienced in the care of bariatric surgical patients . Patients in both groups did not pay any medical costs generated by the study . The human ethics committees of The Alfred Hospital and The Avenue Hospital approved the study in accordance with the guidelines of the National Health and Medical Research Council ( www.nhmrc.gov.au/publications/synopses/e35syn.htm ) and with the Helsinki Declaration of 1975 , as revised in 2000 ( www.wma.net/e/ethicsunit/pdf/draft_historical_contemporary_perspectives.pdf ) . Inclusion Criteria We considered patients to be eligible if they were between 20 and 50 years of age ; had a body mass index of 30 kg/m2 to 35 kg/m2 ; had identifiable problems , including an obesity-related comorbid condition ( such as hypertension , dyslipidemia , diabetes , obstructive sleep apnea , or gastroesophageal reflux disease ) , severe physical limitations , or clinical ly significant psychosocial problems associated with their obesity ; had attempted to reduce weight over at least the previous 5 years ; could underst and the options offered and the r and omization process ; and were willing to comply with the requirements of each program . Exclusion Criteria We excluded c and i date s with a history of bariatric surgery or medical problems that contraindicated treatment in either study group , such as impaired mental status , drug or alcohol addiction , or portal hypertension . In addition , we excluded participants if they had undergone an intensive , physician-supervised program that used very-low-calorie diets or pharmacotherapy or if they did not attend the 2 initial patient information visits . Assessment We provided detailed information about the problems of obesity and about the 2 study groups through at least 2 discussion periods and a patient information booklet . Initial assessment included anthropometric measures ; identification of medical , physical , or psychosocial problems ( both weight-related and other ) ; and a discussion of previous weight loss efforts . The assessment included a detailed dietary history by the trial dietitian and a review by a specialist physician to determine the presence and severity of associated medical conditions . Initial investigations included measurements of fasting blood glucose level ; serum insulin level ; and a lipid profile , including HDL cholesterol and LDL cholesterol levels . After initial assessment , we instituted a program of advice on appropriate eating patterns and exercise and followed each patient on a monthly basis for 3 months . During this time , we assessed the patients ' fulfillment of tasks , such as completion of a food diary , and overall adherence to appointments . R and omization Process We r and omly allocated eligible patients to receive a conventional , intensive , nonsurgical program or laparoscopic adjustable gastric b and ing . A computer-derived r and om allocation sequence , without blocking or stratification , performed the r and omization . This was prepared at the trial office . The trial coordinator enrolled participants and informed them of the trial allocation . After assessment had confirmed a participant 's suitability for r and omization , the coordinator contacted the trial office by telephone for allocation . The study was not blinded . Description of Nonsurgical and Surgical Interventions Common Program We instructed and encouraged all patients to follow appropriate lifestyle behavior of good eating practice s and increased exercise and activity . We also encouraged them to exercise for at least 200 minutes per week . Nonsurgical Program This program centered on the use of behavioral modification , very-low-calorie diet , and pharmacotherapy with education and professional support on appropriate eating and exercise behavior . During the 2-year period , 3 trained physicians developed a program using all the available modalities for each individual on the basis of guidelines prepared and continually review ed by a panel of experienced bariatric physicians . The program began with an intensive 6-month period of very-low-calorie diet ( 500 to 550 kcal/d ) using 1 to 3 packets of Optifast ( Novartis , Fremont , Michigan ) daily for 12 weeks , followed by a transition phase over 4 weeks combining some very-low-calorie meals with 120 mg of orlistat before nonvery-low-calorie diet meals , and then 120 mg of orlistat before all meals until the completion of the intensive phase . This intensive 6-month program was followed by further courses of very-low-calorie diets or orlistat as tolerated , as well as continual behavioral , dietary , and exercise advice to assist the participant in maintaining weight loss over a prolonged period . Sibutramine was not approved for use in Australia during the first 12 months of the study and , therefore , was not incorporated into the medical program . The management program for each individual was design ed to reflect good clinical practice . A physician saw each patient every 2 weeks during the very-low-calorie diet program and every 4 to 6 weeks during the rest of the study . All patients were seen at least every 6 weeks . Surgical Program Two experienced surgeons performed the laparoscopic adjustable gastric b and ( LAP-B AND System ) procedure , by a st and ardized method ( 14 ) , within 1 month of r and omization . The b and was placed along the perigastric pathway in all cases ( 16 ) . The treating surgeon review ed patient progress every 4 to 6 weeks during the study period and made adjustments to the volume of saline within the b and in the office by using st and ard clinical criteria ( 17 ) . Adverse Events All patients in the study were question ed about the occurrence of adverse events at each consultation , and physicians recorded the", "Vertical b and ed gastroplasty ( VBGP ) was compared with Roux-en-Y gastric bypass ( RYGBP ) in a r and omized prospect i ve trial that included preoperative dietary separation of \" sweets eaters \" versus \" non-sweets eaters . \" R and omization was stopped at 9 months after 20 patients had undergone each procedure because a greater weight loss ( p less than 0.05 ) was noted after RYGBP than VBGP . This difference became more significant ( p less than 0.001 ) at each 3-month interval through 3 years , when patients who had VBGPs had lost 37 + /- 20 % of excess weight compared with 64 + /- 19 % for patients who had RYGBPs . The members of the groups were comparable with regard to age , sex , eating habits , morbidity rates before surgery , ideal body weight , and weight before surgery . Although there was no significant difference between the loss of excess weight in \" sweets eaters \" ( 69 + /- 17 % ) or \" non-sweets eaters \" ( 67 + /- 17 % ) after RYGBP at 1 year , \" sweets eaters \" who had VBGPs lost significantly less excess weight ( 36 + /- 13 % ) than did \" non-sweets eaters \" who had VBGPs ( 57 + /- 18 % ) , p less than 0.02 , or \" sweets eaters \" who had RYGBPs , p less than 0.0001 . No significant differences were noted for electrolytes , renal or liver function tests , and most vitamins between patients who had VBGPs and RYGBPs ; however , patients who had RYGBPs had lower ( p less than 0.05 ) serum vitamin B12 levels ( 286 + /- 149 pg/dl ) than did patients who had VBGPs ( 461 + /- 226 pg/dl ) at 2 years . By 3 years , the vitamin B12 levels were equal in members of the two groups . Five patients who had RYGBPs required endoscopic stomal dilatation for stomal stenosis and one had a marginal ulcer develop , which responded to cimetidine . RYGBP was clearly superior to VBGP for \" sweets eaters , \" probably because of the development of dumping syndrome symptoms . However , RYGBP was associated with a larger number of correctable problems . Thus , it is important to evaluate a patient 's eating habits before surgery for morbid obesity ; \" non-sweets eaters \" probably should be treated with VBGP and \" sweets eaters \" with RYGBP", "Horizontal and vertical b and ed gastroplasty ( GP ) were compared as to their effectiveness and side-effects in patients pre-treated for morbid obesity with a very-low-calorie formula diet ( VLCD ) . The pre-treatment served to select the compliant patients , to minimize the surgical hazard , and to optimize the total weight reduction . Seventy-four consecutive patients ( median age 34 years , median body weight 125.1 kg , and median overweight 93 per cent ) were included according to the criteria for entry . The median weight loss on VLCD was 25.7 kg ( range , 5.8 - 92.6 kg ) and the median overweight reduction reached 46 per cent of the initial overweight ( range , 9 - 83 per cent ) . Only few and mild side-effects were observed . Sixty-nine per cent of the patients fulfilled our criterion for surgery by reducing their initial overweight by at least 40 per cent . Of these , 23 and 22 patients were assigned respectively to either vertical b and ed or to horizontal GP . Patients and dietitians were not informed of the assignment . A significant weight loss occurred in both groups . Three months after surgery weight loss after vertical b and ed GP proved to be the larger ( P less than 0.001 ) . The difference became even more pronounced due to an earlier regain among patients treated with the horizontal GP . Thus , at 12 months , the net weight loss after surgery was 9.7 kg ( range , -28.2 - 28.7 kg ) in the vertical b and ed GP group and -1.0 kg ( range , -15.0 - 36.5 kg ) in patients treated with horizontal GP ( P less than 0.0005 ) . At this time , the total weight loss in the groups was 48.5 kg ( range , 6.4 - 104.0 kg ) and 32.6 ( range , 3.7 - 125.1 kg ) respectively ( P less than 0.02 ) , and the total reduction of overweight was greater in the group treated with vertical b and ed GP ( 80 per cent ( range , 10 - 96 ) versus 56 per cent ( range , 8 - 92 ) , P less than 0.005 ) . There were no deaths , and side-effects to VLCD as well as to GP were generally mild . It is concluded that vertical b and ed GP is more effective than horizontal GP and that the former operation adds a significant weight loss to that obtained by VLCD . The combined treatments offer a weight reduction comparable to that observed after jejunoileal bypass . However , some regain within 1 year makes it question able if the vertical b and ed GP is sufficient to prevent weight regain", "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", "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 jejunum and 25 cm of terminal ileum , the bypassed segment of small bowel being decompressed by an end-to-side ileocolostomy . There were 32 patients in the gastric group and 27 in the jejunoileal group . The two groups were comparable in age , preoperative weight and height . There were no postoperative deaths , but the gastric bypass operation was associated with a slightly higher early complication rate indicating it is a more technically dem and ing procedure . Late sequellae were more prominent in the jejunoileal bypass group and included significant diarrhea in 56 % and need for medication in 74 % . Kidney stones and cholelithiasis also complicated the jejunoileal group and were not seen after gastric bypass . All patients showed fatty metamorphosis on the original liver biopsy . This had worsened in 75 % of the jejunoileal group at one year whereas it had improved or was stable in all of the patients in the gastric group", "OBJECTIVE To compare the clinical results of adjustable gastric b and ing and vertical b and ed gastroplasty for morbid obesity . DESIGN Prospect i ve r and omised trial . SETTING University hospital , Sweden . PATIENTS 59 morbidly obese patients , listed for obesity surgery . INTERVENTIONS Adjustable gastric b and ing ( n = 29 ) or vertical b and ed gastroplasty ( n = 30 ) . MAIN OUTCOME MEASURES Weight loss , complications , need for revisional surgery , reflux symptoms and the patient 's own evaluation . RESULTS Five years after surgery the mean ( SEM ) weight reduction for adjustable gastric b and ing was 43 ( 3.0 ) kg and for vertical b and ed gastroplasty 35 ( 4.8 ) kg . One patient in each group died of unrelated causes during follow-up and 3 and 2 patients , respectively , were lost to follow-up . One patient in the vertical b and ed group required reoperation for an anastomotic leak on the third postoperative day . A total of 3 patients in the adjustable group required reoperation and 11 in the vertical b and ed group . CONCLUSIONS Adjustable gastric b and ing carries a smaller risk of reoperation than vertical b and ed gastroplasty and the weight reduction is in the same order of magnitude", "The efficacy of three gastric restriction operations were compared in a prospect i ve r and omized study of 310 morbidly obese subjects . The median patient age was 34 years ( range , 18 to 62 years ) . They were predominantly female ( 13:1 ) and had a median pre-operative weight that was 198 % of their ideal weight ( range , 160 % to 318 % ) . There was an equitable dispersion of perceived risk factors between the groups under study and there were no deaths during the perioperative period . Compliance with follow-up at 3 years was 91 % . When success was defined as a loss of more than 50 % of excess weight or a current pregnancy , the success rates at 3 years were 17 % for gastrogastrostomy , 48 % for vertical gastroplasty , and 67 % for Roux-en-Y gastric bypass ( p less than 0.001 ) . Although the gastric bypass operation took longer to perform , there were similar outcome patterns for the three groups during the postoperative period . We conclude that the Roux-en-Y gastric bypass is the preferred procedure for the surgical treatment of morbid obesity", "CONTEXT Obesity is a major health problem in the United States , but the number of obesity-attributable deaths has not been rigorously estimated . OBJECTIVE To estimate the number of deaths , annually , attributable to obesity among US adults . DESIGN Data from 5 prospect i ve cohort studies ( the Alameda Community Health Study , the Framingham Heart Study , the Tecumseh Community Health Study , the American Cancer Society Cancer Prevention Study I , and the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study ) and 1 published study ( the Nurses ' Health Study ) in conjunction with 1991 national statistics on body mass index distributions , population size , and overall deaths . SUBJECTS Adults , 18 years or older in 1991 , classified by body mass index ( kg/m2 ) as overweight ( 25 - 30 ) , obese ( 30 - 35 ) , and severely obese ( > 35 ) . MAIN OUTCOME MEASURE Relative hazard ratio ( HR ) of death for obese or overweight persons . RESULTS The estimated number of annual deaths attributable to obesity varied with the cohort used to calculate the HRs , but findings were consistent overall . More than 80 % of the estimated obesity-attributable deaths occurred among individuals with a body mass index of more than 30 kg/m2 . When HRs were estimated for all eligible subjects from all 6 studies , the mean estimate of deaths attributable to obesity in the United States was 280184 ( range , 236111 - 341153 ) . Hazard ratios also were calculated from data for nonsmokers or never-smokers only . When these HRs were applied to the entire population ( assuming the HR applied to all individuals ) , the mean estimate for obesity-attributable death was 324 940 ( range , 262541 - 383410 ) . CONCLUSIONS The estimated number of annual deaths attributable to obesity among US adults is approximately 280000 based on HRs from all subjects and 325000 based on HRs from only nonsmokers and never-smokers", "For physicians , pharmacists , pharmacologists , and others , the medical literature is a key source of information about prescription drugs [ 1 , 2 ] . The medical literature on drugs includes articles from peer- review ed journals , non-peer- review ed ( controlled circulation or throwaway ) journals , and the published proceedings of symposia [ 3 , 4 ] . Symposia are a rapidly growing and potentially major means of disseminating information about drugs . In the clinical journals with the highest circulation rates , the number of symposia published increased from 83 during 1972 - 1977 to 307 during 1984 - 1989 . Approximately half of these symposia were on pharmaceutical topics [ 4 ] . Symposia can be valuable sources of information about drugs , but evidence suggests that they can also be used to market drugs and other interventions , especially if they are industry sponsored . Approximately 70 % of symposia on pharmaceutical topics are sponsored by drug companies [ 3 , 4 ] . Among symposia , sponsorship by a single drug company is associated with promotional characteristics that include a focus on a single drug , misleading titles , use of br and names , and lack of peer review [ 4 ] . Other studies indicate that clinical trials , including those published in symposia , are more likely to favor a new drug therapy if they are funded by the pharmaceutical industry than if they are not [ 5 , 6 ] . Although physicians often report that the peer- review ed literature is one of their main sources of drug information , industry sources of information can sometimes have a stronger influence on prescribing behavior [ 2 ] . Thus , if symposia sponsored by drug companies are a growing source of information about drugs for pharmacists and physicians , assessing the quality of the articles in these symposia is important . We compared the method ologic quality and relevance of drug studies published in symposia sponsored by single drug companies with those of studies that were published in symposia that had other sponsors or in the peer- review ed parent journals . We also assessed whether a methods section was present , because such a section is necessary for evaluating quality . Finally , we tested whether drug industry support of research was associated with study outcome . Methods A symposium is a collection of papers published as a separate issue or as a special section in a regular issue of a medical journal [ 4 ] . We defined original clinical drug articles as articles that 1 ) appeared to present original data from studies done in humans [ that is , articles that had at least one table or figure that was not acknowledged to have been reprinted from another source ] and 2 ) did not specifically state that they were review s [ 4 ] . Selection of Articles We identified original clinical drug articles that had a section describing the study methods , because such a section is needed to assess the quality of an article . Using a computer-generated list of r and om numbers from 1 to 625 , we r and omly selected symposia from 625 symposia that had been identified for a previous study [ 4 ] . We had data on the type of sponsorship of publication for each symposium . From each selected symposium , we r and omly selected one original clinical drug article that had a methods section . We continued selecting symposia until we had enough articles ( n = 127 ) according to the sample size estimates described below . We also calculated the proportion of articles in the selected symposia , overall and by type of sponsorship , that had methods sections . Quality Assessment We compared the quality of original clinical drug articles published in symposia sponsored by single drug companies with that of similar articles published in symposia that had other sponsors and in the peer- review ed parent journals . Sample Size Estimates We estimated the sample size needed to test the association between the independent variable type of sponsorship of publication and the main outcome measure , method ologic quality score . For a three-group comparison , a minimum sample of 108 symposium articles was needed to detect a minimum effect size of 0.10 ( on a scale of 0 to 1 ) , with an value of 0.05 and a value of 0.80 , and st and ard deviation of quality scores of 0.18 based on previous results [ 7 ] . To compare articles from symposia sponsored by single pharmaceutical companies with articles from the peer- review ed parent journals , we estimated that we would need 45 symposia articles and 45 journal articles ; this estimate was the result of sample size calculations done using the variables described above . Because date of publication , journal , and therapeutic class of drug could have confounded the association between source of publication and quality [ 8 - 10 ] , we matched each symposium article to an article from the parent journal by using these characteristics , as described previously [ 7 ] . Our sample of symposium articles contained 50 articles sponsored by single drug companies , but 5 articles published in Transplantation Proceedings were excluded from this analysis because no parent journal is associated with that publication . Instruments We used previously developed instruments to measure the method ologic quality of articles ( defined as the minimization of systematic bias and the consistency of conclusions with results ) and non method ologic indices of quality , such as clinical relevance and generalizability . Both instruments were valid and reliable and have been published elsewhere [ 7 ] . Four review ers independently assessed each article : Two used the method ologic quality instrument , and two used the clinical relevance instrument . We derived method ologic quality and clinical relevance scores for each article by using a previously described scoring system [ 7 ] . Each score was between 0 ( lowest quality ) and 1 ( highest quality ) and was the average of the scores of the two review ers . Two clinical pharmacologists with extensive research experience in the health sciences did the method ologic quality assessment . For the clinical relevance instrument , three pairs of review ers with clinical experience in general internal medicine and research experience in the health sciences each assessed one third of the articles . Each pair of review ers review ed the articles in the same r and omized order . For both instruments , review ers were trained as described previously [ 7 ] . For the quality assessment s , each review er worked independently , was blinded as to whether an article had been published in a symposium , and was given photocopies of articles from which author names , institution names , journal names , date s , and all other reference information had been obliterated . Review ers were unaware of our hypotheses and the purpose of their review ing , and they were paid for their work . None of the review ers were known to us or knew of our previous work before the study . We assessed the inter-rater reliability of quality scores by using the Kendall coefficient of concordance ( W ) with adjustment for tied ranks [ 11 ] and the intraclass correlation ( R ; treating both review ers and articles as r and om effects [ 12 ] ) . Inter-rater reliability of quality scores was high ( for method ologic quality scores : W equals 0.85 , R equals 0.74 [ 95 % CI , 0.67 to 0.80 ] ; for clinical relevance scores : W equals 0.77 , R equals 0.56 [ CI , 0.44 to 0.65 ] ) . Drug Company Support and Study Outcome For each article , one of us determined whether a drug company had supported the research and whether the article 1 ) reported an outcome favorable to the drug of interest , 2 ) did not report an outcome favorable to the drug of interest , or 3 ) did not test a hypothesis . The drug of interest ( as defined from the perspective of the authors , according to Gotzsche [ 13 ] ) was the newest drug if two or more drugs were studied . We defined research as having had drug company support if the article that reported the research acknowledged either that a drug company had provided funding or drugs or that any of the authors were employed by a drug company . We determined drug company support solely on the basis of information in the paper . If an article did not test a hypothesis , it was excluded from this analysis . We classified the remaining articles as favorable or unfavorable using Gotzsche 's definitions [ 13 ] . An article was favorable if the drug that seemed to be of primary interest to the authors had the same effect as the comparison drug or drugs but with less pronounced side effects , had a better effect without more pronounced side effects , or was preferred more often by patients when the effect and side-effect evaluations were combined . All other articles were considered not favorable . The conclusions of the authors were taken at face value , even if they conflicted with the study results . To test inter-rater reliability , the other author independently assessed a subset of the articles ( n = 90 ) . Agreement in classifying articles as favorable or not favorable was 85 % . Statistical Analyses Because method ologic quality and relevance scores were distributed normally ( Shapiro-Wilk test ) , we analyzed differences between groups ( type of sponsorship of publication ) by using parametric one-way analysis of variance followed by the Tukey test for multiple comparisons or two-way analysis of variance ( total error rate , 0.05 ) . We compared matched groups ( symposium articles and peer- review ed parent journal articles ) by using the paired t-test ( two-tailed equals 0.05 ) . To analyze categorical data on the outcome of studies , we tested for differences in proportions between groups by using the chi-square statistic . For tests of significance , we used an value of 0.05 . All hypothesis tests were two-sided . Results Presence of a Method Section To obtain 127 original clinical drug articles for quality assessment , we had to select 213 symposia containing a total of 5041 articles . The proportions of articles that reported original data but contained no methods sections were 4 % overall ( 195 of 5041 ) , 10 % ( 108 of 1064 ) in the symposia sponsored by single drug companies", "Laparoscopic techniques have been developed for performing Roux‐en‐$\\font\\ss = cmss10 scaled 1000 \\hbox{Y}$ gastric bypass ( LRYGBP ) and vertical b and ed gastroplasty ( LVBG ) in patients with morbid obesity . It is not certain , however , which is the better technique in non‐superobese patients ( body mass index less than 50 kg/m2 ) ", "Objective : To compare , in a prospect i ve , r and omized , single-institution trial laparoscopic adjustable silicone gastric b and ing ( LASGB ) with laparoscopic vertical b and ed gastroplasty ( LVBG ) in morbidly obese patients . Summary Background Data : LASGB is a simple and safe procedure , but some reports have suggested disappointing long-term results . Despite the recent widespread use of LASGB , there are no prospect i ve nor r and omized trials comparing LASGB with other laparoscopic procedures . Methods : A total of 100 morbidly obese patients , with body mass index ( BMI ) 40 to 50 kg/m2 , without compulsive eating , were r and omized to either LASGB ( n = 49 ) or LVBG ( n = 51 ) . Minimum follow-up was 2 years ( mean 33.1 months ) . Results : There were no deaths or conversions in either group . Mean operative time was 94.2 minutes in LVBGs and 65.4 in LASGBs ( P Early morbidity rate was lower in LASGBs ( 6.1 % ) versus LVBGs ( 9.8 % ) ( P = 0.754 ) . Mean hospital stay was shorter in LASGBs versus LVBGs : 3.7 days versus 6.6 ( P Late complications rate in LVBGs was 14 % ( 7 of 50 ) and in LASGBs 32.7 % ( 16 of 49 ) ( P slippage of the b and ( 18 % ) . Late reoperations rate in LVBGs was 0 % ( 0 of 50 ) versus 24.5 % ( 12 of 49 ) in LASGBs ( P Excess weight loss in LVBGs was , at 2 years , 63.5 % and , at 3 years , 58.9 % ; in LASGBs , excess weight loss , respectively , was 41.4 % and 39 % . BMI in LVBGs was , at 2 years , 29.7 kg/m2 and , at 3 years , 30.7 kg/m2 ; in LASGBs , BMI was 34.8 kg/m2 at 2 years and 35.7 kg/m2 at 3 years . According to Reinhold 's classification , a residual excess weight LASGB ( P patients with BMI 40 to 50 kg/m2 , LASGB requires shorter operative time and hospital stay but LVBG is more effective in terms of late complications , reoperations , and weight loss", "Objectives : This prospect i ve , r and omized trial compared the safety and effectiveness of laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) and laparoscopic mini-gastric bypass ( LMGBP ) in the treatment of morbid obesity . Summary Background Data : LRYGBP has been the gold st and ard for the treatment of morbid obesity . While LMGBP has been reported to be a simple and effective treatment , data from a r and omized trial are lacking . Methods : Eighty patients who met the NIH criteria were recruited and r and omized to receive either LRYGBP ( n = 40 ) or LMGBP ( n = 40 ) . The minimum postoperative follow-up was 2 years ( mean , 31.3 months ) . Perioperative data were assessed . Late complication , excess weight loss , BMI , quality of life , and comorbidities were determined . Changes in quality of life were assessed using the Gastro-Intestinal Quality of Life Index ( GIQLI ) . Results : There was one conversion ( 2.5 % ) in the LRYGBP group . Operation time was shorter in LMGBP group ( 205 versus 148 , P no mortality in each group . The operative morbidity rate was higher in the LRYGBP group ( 20 % versus 7.5 % , P late complications rate was the same in the 2 groups ( 7.5 % ) with no reoperation . The percentage of excess weight loss was 58.7 % and 60.0 % at 1 and 2 years , respectively , in the LPYGBP group , and 64.9 % and 64.4 % in the LMGBP group . The residual excess weight LMGBP group ( P obesity-related clinical parameters and complete resolution of metabolic syndrome in both groups were noted . Both gastrointestinal quality of life increased significantly without any significant difference between the groups . Conclusion : Both LRYGBP and LMGBP are effective for morbid obesity with similar results for resolution of metabolic syndrome and improvement of quality of life . LMGBP is a simpler and safer procedure that has no disadvantage compared with LRYGBP at 2 years of follow-up", "A r and omized prospect i ve comparison of 50 modified Gomez gastric partitioning to 50 subtotal gastric exclusion ( bypass ) operations is presented . Smaller pouch sizes than are generally recommended were used , along with accurate calibration of the outlet size by suturing around a 30F bougie in both operations . It is believed that these techniques improved weight loss with minimal increase in side effects , but some increase in the length of hospital stay to ensure adequate fluid intake . Significantly better weight loss and less need for reoperation was found with gastric exclusion , and the complication rates were similar . Either operation requires meticulous attention to detail and follow-up to achieve low mortality and morbidity rates and good weight loss ; but , if these are accomplished , the best end results statistically strongly favor subtotal gastric exclusion", "Background : Gastric bypass and adjustable gastric b and ing are the 2 most commonly performed bariatric procedures for the treatment of morbid obesity . The aim of this study was to compare the outcomes , quality of life , and costs of laparoscopic gastric bypass versus laparoscopic gastric b and ing . Study Design : Between 2002 and 2007 , 250 patients with a body mass index of 35 to 60 kg/m2 were r and omly assigned to gastric bypass or gastric b and ing . After exclusion , 111 patients underwent gastric bypass and 86 patients underwent gastric b and ing . Outcome measures included demographic data , operative time , blood loss , length of hospital stay , morbidity , mortality , early and late reoperation rate , weight loss , changes in quality of life , and cost . Treatment failure was defined as losing less than 20 % of excess weight or conversion to another bariatric operation for failure of weight loss . Results : There were no deaths at 90 days in either group . The mean body mass index was higher in the gastric bypass group ( 47.5 vs. 45.5 kg/m2 , respectively , P gastric b and ing , operative blood loss was higher and the mean operative time and length of stay were longer in the gastric bypass group . The 30-day complication rate was higher after gastric bypass ( 21.6 % vs. 7.0 % for gastric b and ) ; however , there were no life-threatening complications such as leaks or sepsis . The most frequent late complication in the gastric bypass group was stricture ( 14.3 % ) . The 1-year mortality was 0.9 % for the gastric bypass group and 0 % for the gastric b and group . The percent of excess weight loss at 4 years was higher in the gastric bypass group ( 68 ± 19 % vs. 45 ± 28 % , respectively , P Treatment failure occurred in 16.7 % of the patients who underwent gastric b and ing and in 0 % of those who underwent gastric bypass , with male gender being a predictive factor for poor weight loss after gastric b and ing . At 1-year postsurgery , quality of life improved in both groups to that of US norms . The total cost was higher for gastric bypass as compared with gastric b and ing procedure ( $ 12,310 vs. $ 10,766 , respectively , P and gastric b and ing are both safe and effective approaches for the treatment of morbid obesity . Gastric bypass result ed in better weight loss at medium- and long-term follow-up but was associated with more perioperative and late complications and a higher 30-day readmission rate . There was a wide variation in weight loss after gastric b and ing with a small proportion of patients considered as treatment failure , and male gender was a predictive factor for poor weight loss", "BACKGROUND It is well known that citizens of developed countries are more likely to be overweight than they were 20 years ago . The most serious health problems are not associated with overweight or moderate obesity , however , but with clinical ly severe or morbid obesity ( e.g. more than 100 pounds ( 45 kg ) overweight ) . There is no reason to expect that morbid obesity trends parallel overweight or moderate obesity . If morbid obesity is a rare pathological condition that has biological causes , the more than 10-fold increase in bariatric surgery procedures over the past eight years in the USA could have even lowered the prevalence of morbid obesity- and may very well stem the problem in other countries . OBJECTIVE To estimate trends for extreme weight categories ( BMI > 40 and > 50 ) for the period between 1986 and 2005 in the USA , and to investigate whether trends have changed since 2000 . METHODS Data from The Behavioral Risk Factor Surveillance System ( a r and om-digit telephone survey of the household population of the USA ) , for the period from 1986 to 2005 , were analysed . The main outcome measure was body mass index ( BMI ) , calculated from self-reported weight and height . RESULTS From 2000 to 2005 , the prevalence of obesity ( self-reported BMI over 30 ) increased by 24 % . However , the prevalence of a ( self-reported ) BMI over 40 ( about 100 pounds ( 45 kg ) overweight ) increased by 50 % and the prevalence of a BMI over 50 increased by 75 % , two and three times faster , respectively . The heaviest BMI groups have been increasing at the fastest rates for 20 years . CONCLUSIONS The prevalence of clinical ly severe obesity is increasing at a much faster rate among adults in the USA than is the prevalence of moderate obesity . This is consistent with the public health idea that the population weight distribution is shifting , which disproportionately increases extreme weight categories . Because comorbidities and result ing service use are much higher among severely obese individuals , the widely published trends for overweight/obesity underestimate the consequences for population health . The aggressive and costly expansion of bariatric surgery in recent years has had no visible effect on containing morbid obesity rates in the USA", "One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease ( CHD ) risk . A cross-sectional study was design ed to r and omly assign 79 morbidly obese subjects ( 27 men and 52 women ; age : 30 - 45 years ) either to a diet protocol ( 20 kcal per kg fat-free mass ( FFM ) ; 55 % carbohydrates , 30 % fat , and 15 % proteins ) or to malabsorptive surgery ( biliopancreatic diversion ) . Fatness parameters , measured by dual-energy X-ray absorptiometry , lipid profile , insulin , leptin , sex steroid hormones and sex hormone-binding globulin ( SHBG ) levels were compared at baseline and 1 year after the beginning of the study . The data showed that plasma SHBG levels , but not testosterone levels , correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women . Total leptin levels were significantly lower ( P plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG , but not insulin levels , were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients . The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness . Finally , in obese patients , SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis", "Background : Vertical b and ed gastroplasty ( VBG ) and gastric bypass ( GBP ) are the two bariatric procedures recommended by NIH consensus conference . Recent advancement in laparoscopic ( L ) techniques has made LVBG and LGBP alternatives for the conventional open approach . Methods : From December 2000 to February 2002 , 80 patients ( 24 men and 56 women ; mean age 32 years , range 18 - 57 ) with morbid obesity ( mean BMI 43.2 kg/m2 , range 36 - 59.8 ) were enrolled in a prospect i ve trial and r and omly assigned to LVBG or LGBP . Changes in quality of life were assessed using the Gastro-intestinal quality of life index ( GIQLI ) . Results : The conversion rate was zero for LVBG and 2.5 % ( 1/40 ) for LGBP . There has been no mortality . Surgical time was significantly longer for LGBP ( 209 minvs 126 min for LVBG , P hospital stay was 3.5 days for the LVBG vs 5.7 days for LGBP ( P Postoperative analgesic usage was also less for LVBG patients ( mean dose 1.4 vs 2.4 , P Early complication rate was higher in the LGBP group ( 17.8 % vs 2.5 % , P anastomotic leakage ( 5 % ) . Late complications consisted of upper GI bleeding , stenosis and others observed in 4 LGBP patients ( 10 % ) and 2 LVBG patients ( 5 % ) . Mean follow-up was 20 months ( range 18 to 30 ) . BMI fell significantly in both groups , with significant improvement of obesity-related co-morbidities . LGBP had significantly better excess weight loss than LVBG ( 62.9 % vs 55.4 % at 1 year and 71.4 % vs 53.1 % at 2 years ) , as well as lower BMI than LVBG ( 29.6 vs 31.1 at 1 year and 28.5 vs 31.9 at 2 years ) . There was no difference in the reduction of obesity-related laboratory abnormalities at 1 year except a lower hemoglobin in LGBP ( 11.8 vs 13.8 , P Preoperative GIQLI scores were similar between the groups ; however , at 1 year , LGBP patients had better GIOLI scores than LVBG patients ( 121 vs 106 , P LVBG had improvement in physical condition , social function and emotional conditioning but deterioration in GI symptoms which result ed in no increase in total GIQLI score . Conclusion : LGBP was a time-consuming dem and ing technique with a higher early complication rate compared with LVBG . Although both operations result ed in significant weight reduction and decrease in obesity-related co-morbidities , LGBP had a trend of greater weight loss and significantly better GIQLI than LVBG at the cost of a significant long-term trace element deficiency state . Each patient should be individualized for the operations according to the patient 's decision", "Background : Different changes of plasma ghrelin levels have been reported following gastric b and ing , Roux-en-Y gastric bypass , and biliopancreatic diversion . Methods : This prospect i ve study compares plasma ghrelin levels and weight loss following laparoscopic sleeve gastrectomy ( LSG ) and laparoscopic adjustable gastric b and ing ( LAGB ) in 20 patients . Results : Patients who underwent LSG ( n=10 ) showed a significant decrease of plasma ghrelin at day 1 compared to preoperative values ( 35.8 ± 12.3 fmol/ml vs 109.6 ± 32.6 fmol/ml , P=0.005 ) . Plasma ghrelin remained low and stable at 1 and 6 months postoperatively . In contrast , no change of plasma ghrelin at day 1 ( 71.8 ± 35.3 fmol/ml vs 73.7 ± 24.8 fmol/ml , P=0.441 ) was found in patients after LAGB ( n=10 ) . Increased plasma ghrelin levels compared with the preoperative levels at 1 ( 101.9 ± 30.3 fmol/ml vs 73.7 ± 24.8 fmol/ml , P=0.028 ) and 6 months ( 104.9 ± 51.1 fmol/ml vs 73.7 ± 24.8 fmol/ml , P=0.012 ) after surgery were observed . Mean excess weight loss was higher in the LSG group at 1 ( 30 ± 13 % vs 17 ± 7 % , P=0.005 ) and 6 months ( 61 ± 16 % vs 29 ± 11 % , P=0.001 ) compared with the LAGB group . Conclusions : As a consequence of resection of the gastric fundus , the predominant area of human ghrelin production , ghrelin is significantly reduced after LSG but not after LAGB . This reduction remains stable at follow-up 6 months postoperatively , which may contribute to the superior weight loss when compared with LAGB ", "AIM : To determine whether visceral fat reduction in connection with bariatric surgery could improve weight loss and metabolic profile of obese subjects . PATIENTS AND METHODS : In a one-center , r and omized and controlled pilot trial we assigned 50 subjects with severe obesity ( body mass index > 35 kg/m2 ) to either adjustable gastric b and ing ( AGB ) alone ( 11 men and 14 women ) , or AGB plus surgical removal of the total greater omentum ( 11 men and 14 women ) . The patients were followed at regular intervals for 2 y and examined at 0 and 24 months with respect to body composition and metabolic profile . RESULTS : No significant differences between control and omentectomized patients were observed at baseline . The removed greater omentum constituted 0.8±0.4 % ( mean±s.d . ) of total body fat . At 2 y follow-up there was an expected decrease in body weight and an improvement in metabolic profile in both groups . Although omentectomized subjects tended to lose more weight than control subjects the difference was not statistically significant and changes in waist-to-hip ratio and saggital diameter did not differ between groups . However , the improvements in oral glucose tolerance , insulin sensitivity and fasting plasma glucose and insulin were 2–3 times greater in omentectomized as compared to control subjects ( P from 0.009 to 0.04 ) , which was statistically independent of the loss in body mass index . No differences in blood lipids between the groups were recorded . No adverse effects related to omentectomy were observed . CONCLUSIONS : Omentectomy , when performed together with AGB , has significant positive and long-term effects on the glucose and insulin metabolic profiles in obese subjects", "OBJECTIVE To assess the effect of vertical b and ed gastroplasty and gastric b and ing on the development of gastro-oesophageal reflux using both subjective and objective methods . DESIGN Prospect i ve , r and omised study . SETTING Teaching hospital , Sweden . SUBJECTS 50 consecutive , morbidly obese patients ( mean ( SD ) body mass index ( BMI ) 42.5 ( 5 ) , 27 women and 23 men ; mean age 48 years , range 38 - 57 years ) . INTERVENTIONS Vertical b and ed gastroplasty ( n = 24 ) or gastric b and ing ( n = 26 ) . MAIN OUTCOME MEASURES Results of evaluation by st and ardised question naire , 24-hour ambulatory pH-metry , and endoscopy . RESULTS After six months the mean ( SD ) BMI had decreased to 34.4 ( 5.7 ) , with no differences between the groups . Mild dysphagia was somewhat more common ( 13 compared with 1 ) but the incidence of heartburn ( 8 compared with 17 ) , and acid regurgitation ( 12 compared with 14 ) were less after the operation ; 3 patients developed erosive oesophagitis , two in the vertical b and ed group and one in the b and ing group . Ambulatory pH-metry readings did not change significantly from preoperatively and there were no differences between the two operations . One patient developed pathological reflux , and in three the values returned to the normal range . CONCLUSION Gastric restriction operations including those with a narrow stoma that causes outflow obstruction do not seem to increase the incidence of reflux in patients with functioning antireflux barriers", "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", "A prospect i ve , r and omized trial comparing vertical b and ed gastroplasty ( VBG ) and vertical gastric bypass ( GB ) for obesity was completed in 106 patients who did not differ in baseline body mass index ( BMI = kg/m2 ) or length of follow-up . The goal of this surgery was to return patients to within 50 % of their ideal weight , i.e. , a body mass index less than 35 kg/m2 , and to accomplish this while maintaining a low risk for malnutrition as well as other morbidity and mortality . Success was defined as a BMI less than 35 kg/m2 because the mortality risk increases rapidly above this degree of obesity . Surgical failures were encountered in 43 % of the 54 patients in the VBG group , all of whom had division between the vertical staple lines . The main causes of failure were stenosis and enlargement of the gastroplasty orifice . Surgery failed in 23 % of the GB-treated patients , due to perforation of the vertical staple line . An isolated gastric bypass ( IGB ) not dependent on staples was performed as the remedial operation for the failures of both VBG and GB . IGB was significantly better than VBG or GB , with a success rate of 83 % compared with 39 % for VBG and 58 % for GB . Subsequent experience since completion of this r and omized trial in 54 consecutive patients supports IGB for primary , as well as remedial , operations for the morbidly obese ( BMI = 40 to 50 kg/m2 ) , as well as for patients who are super obese ( BMI greater than 50 kg/m2 ) ", "OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful", "BACKGROUND R and omized controlled trials ( RCTs ) in surgery can provide valuable evidence of the efficacy of interventions if they are well- design ed , appropriately executed , and adequately reported . Adequate reporting of methodology in surgical RCTs is known to be poor , and adverse-event reporting in surgical research is inconsistent . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a framework to help authors report their findings in a transparent manner . Extensions to the CONSORT statement have been published recently to address deficiencies in adverse-event reporting and in reporting of specific criteria related to nonpharmacologic treatments . The aim of this study was to assess the quality of reporting of trial methodology and adverse events in a sample of general surgical RCTs published in high- quality surgical journals using the criteria specified in the CONSORT statements . STUDY DESIGN We used impact factor to identify the top three ranked surgical journals in 2004 . We then obtained information on all RCTs published in these journals in the 2005 calendar year . We assessed quality of reporting using Jadad score , compared the quality of RCTs from CONSORT-endorsing journals with nonendorsers , and assessed the number of RCTs adequately reporting key generic method ologic , adverse-event-related , and specific nonpharmacologic criteria . RESULTS Of 42 RCTs analyzed , only 40 % ( 17 of 42 ) had a Jadad score > or = 3 . There was no significant difference in the number of high- quality RCTs published in CONSORT-endorsing journals compared with nonendorsers ( p = 0.3 ) . The median percentage of RCTs adequately reporting generic method ologic , adverse-event-related , and specific nonpharmacologic criteria was 32.5 % , 17 % , and 36.5 % , respectively . CONCLUSIONS Quality of reporting of generic method ologic , adverse-event-related , and specific nonpharmacologic criteria in surgical RCTs is poor . Increased attention to quality of reporting of surgical RCTs is required if studies are to meet published criteria", "We compared the weight-reducing effect of diet and gastroplasty with that of diet alone in a r and omized trial in 60 morbidly obese patients followed for two years . Initial median body weight was 120 kg in patients r and omly assigned to gastroplasty plus diet and 115 kg in those assigned to diet alone . Maximum weight losses did not differ significantly between the groups ( 26.1 kg in the gastroplasty group and 22.0 kg in the group treated with diet alone , P greater than 0.05 ) . The risk of a Type II error with a true difference larger than 9.5 kg was less than 5 per cent . However , the group treated with diet alone regained significantly more weight after maximum weight loss had been achieved , so that the gastroplasty group had a more favorable net outcome at two years ( P less than 0.05 )", "We present our prospect i ve comparative study on 60 patients subjected to two types of gastric restrictive procedures , i.e. Vertical B and ed Gastroplasty ( VBG ) and Laparoscopic Adjustable Gastric B and ing ( LAGB ) at King Abdul Aziz University Hospital , Jeddah , Saudi Arabia . The aim of our study was to compare weight reduction after both procedures . Thirty patients had VBG and thirty had LAGB based upon informed consents . The age , sex and preoperative weight and BMI were comparable in both groups . Excess weight loss of 87 % was achieved in the VBG group while only 50 % was noticed in the LAGB group at 6 months postoperatively", "Fifty-seven morbidly obese patients were r and omized to gastric bypass ( 29 ) or gastroplasty ( 28 ) and observed for 24 months postoperatively . Operating time and hospital stay were longer and peroperative and postoperative complications somewhat more common in the bypass than in the gastroplasty group . But weight loss at 1 year was significantly greater and failures significantly fewer after gastric bypass . Four gastroplasties were converted to bypass after 18 - 24 months because of failure to lose weight . Gastric bypass was judged to be much the preferable of the two operations . Dumping occurred in some patients with bypass but not after gastroplasty . Dumping was not associated with greater weight loss . Peroperatively measured pouch volume showed significant correlation with weight loss after gastroplasty , but not after bypass . Peroperative pouch volume and postoperatively measured stoma diameter were co-acting factors , which in multiple regression analysis could explain observed variance in weight loss to about 40 % after gastroplasty , but to a negligible degree after gastric bypass", "Background : a prospect i ve r and omized study was undertaken to compare the outcome of vertical b and ed gastroplasty ( VBG ) and gastric bypass ( GBP ) in patients with clinical ly severe obesity . Methods : eligibility criteria included Class IV obesity , Patients were managed conservatively for 3 months prior to surgery . Patients were followed post-operatively and monitored for early and late complications and their weight loss outcome for up to 5 years . Results : 44 patients were recruited . Two patients withdrew within 4 weeks and were excluded . Twenty subjects had a GBP and 22 a VBG . There were no significant differences with respect to age , gender , maximum or pre-operative weight between the groups ( p > 0.05 ) . Patients who underwent GBP demonstrated significantly greater post-operative weight loss ( p no deaths , pulmonary emboli , post-operative leaks or wound dehiscence . There were no instances of staple-line disruption . Symptomatic ulcer disease , confirmed endoscopically , developed in 25 % of GBP patients . Nine patients developed gallstones post-operatively of whom five were in the VBG and four in the GBP group . Conclusions : weight loss following GBP was maintained , while VBG patients slowly regained", "BACKGROUND Obesity is a risk factor for cancer . Intentional weight loss in the obese might protect against malignancy , but evidence is limited . To our knowledge , the Swedish Obese Subjects ( SOS ) study is the first intervention trial in the obese population to provide prospect i ve , controlled cancer-incidence data . METHODS The SOS study started in 1987 and involved 2010 obese patients ( body-mass index [ BMI ] > or=34 kg/m(2 ) in men , and > or=38 kg/m(2 ) in women ) who underwent bariatric surgery and 2037 contemporaneously matched obese controls , who received conventional treatment . While the main endpoint of SOS was overall mortality , the main outcome of this exploratory report was cancer incidence until Dec 31 , 2005 . Cancer follow-up rate was 99.9 % and the median follow-up time was 10.9 years ( range 0 - 18.1 years ) . FINDINGS Bariatric surgery result ed in a sustained mean weight reduction of 19.9 kg ( SD 15.6 kg ) over 10 years , whereas the mean weight change in controls was a gain of 1.3 kg ( SD 13.7 kg ) . The number of first-time cancers after inclusion was lower in the surgery group ( n=117 ) than in the control group ( n=169 ; HR 0.67 , 95 % CI 0.53 - 0.85 , p=0.0009 ) . The sex-treatment interaction p value was 0.054 . In women , the number of first-time cancers after inclusion was lower in the surgery group ( n=79 ) than in the control group ( n=130 ; HR 0.58 , 0.44 - 0.77 ; p=0.0001 ) , whereas there was no effect of surgery in men ( 38 in the surgery group vs 39 in the control group ; HR 0.97 , 0.62 - 1.52 ; p=0.90 ) . Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention . INTERPRETATION Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men . FUNDING Swedish Research Council , Swedish Foundation for Strategic Research , Swedish Federal Government under the LUA/ALF agreement , Hoffmann La Roche , Cederoths , AstraZeneca , Sanofi-Aventis , Ethicon Endosurgery" ]

[ "Abstract Objectives : Approximately one third to one half of the penis is embedded in the pelvis and can be felt through the scrotum and in the perineum . The main arteries and nerves enter the penis through this perineal part of the penis , which seems to represent a highly sensitive area . We investigated the hypothesis that percutaneous perineal stimulation evokes erection in patients with neurogenic erectile dysfunction . Methods : Percutaneous electrostimulation of the perineum ( PESP ) with synchronous intracorporeal pressure ( ICP ) recording was performed in 28 healthy volunteers ( age 36.3 ± 7.4 y ) and 18 patients ( age 36.6 ± 6.8 y ) with complete neurogenic erectile dysfunction ( NED ) . Current was delivered in a sine wave summation fashion . Average maximal voltages and number of stimulations delivered per session were 15 to 18 volts and 15 to 25 stimulations , respectively . Results : PESP of healthy volunteers effected an ICP increase ( P The latent period recorded was 2.5 ± 0.2 seconds . Results were reproducible on repeated PESP in the same subject but with an increase of the latent period . Patients with NED recorded an ICP increase that was lower ( P latent period that was longer ( P : PESP effected ICP increase in the healthy volunteers and patients with NED . The ICP was significantly higher and latent period shorter in the healthy volunteers than in the NED patients . PESP may be of value in the treatment of patients with NED , provided that further studies are performed to reproduce these results", "Our experience with intracavernous injection of prostagl and in E1 in spinal cord injured patients with neurogenic erectile dysfunction included 15 men . They received testing dosage starting from 5 µg with increasing dosage ( maximum 20 µg ) to achieve a rigid erection of Schramek 's grade 5 and lasting for at least 20 min . All of them had achieved functional erection adequate for coitus after treatment except one patient who had been proved to have venogenic impotence . We found that intracavernous injection of prostagl and in E1 had significantly improved the erectile condition . No systemic side effect or any other complication was noted except that pain at the injection site was complained of in two patients with incomplete lesion", "Abstract Background / objective : To show the efficacy , safety , and tolerability of sildenafil in men with erectile dysfunction ( ED ) associated with complete or incomplete spinal cord injury ( SCI ) and to assess its effects on quality of life ( Qol ) using the Life-Satisfaction Check List . Methods : This was a placebo-controlled , multicenter , r and omized , double-blind , flexible-dose , 2-way crossover study with a 2-week washout period between each phase . Patients with ED attributable to SCI(Sexual Health Inventory-Male score ≤21 ) received 50 to 100 mg sildenafil ( n = 24 ) or placebo ( n = 26 ) . Results : Compared with placebo , sildenafil produced higher levels of successful sexual stimulation , intercourse success , satisfaction with sexual life and sexual relationship , erectile function , overall sexual satisfaction , and an improved Erectile Dysfunction Inventory of Treatment Satisfaction score , with no clinical ly relevant effects onvital signs . Sildenafil seemed more effective in patients with incomplete SCI than in those with complete SCI , producing significant improvements , compared with placebo , in a number of measures only in patients with incomplete SCI . All patients who expressed a preference selected sildenafil over placebo , although the drug had no effect on patient Qol . Sildenafil was well tolerated , with a profile comparable to that of placebo . Conclusions : Compared with placebo , treatment with oral sildenafil safely and effectively improved erectile function in patients with ED attributable to SCI , especially in those with incomplete injury , and was theagent of choice in those who expressed a preference", "AIM Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction ( ED ) . Efficacy of vardenafil has been demonstrated in various ED population s , but that in Japanese patients with spinal cord injury ( SCI ) has not been assessed . METHODS This was an open-label , multicenter , flexible dose , 12-week study in patients with ED due to SCI . Following a 4-week observation period , patients received vardenafil 10 mg for 4 weeks , and based on efficacy , tolerability and patient preference , doses for the remaining 8 weeks were decided by investigators . The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function . RESULTS Ten patients took 10 mg all through the study , while 22 patients took 20 mg after completing 4 weeks ' treatment with 10 mg . The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward ( LOCF ) in the former group and from 10.3 to 22.5 in the latter group , respectively . Importantly , there was a 5.0 point increase in erectile function domain score after up-titration in the latter group . Drug-related adverse events were observed in 22 % of patients including hot flushes ( 9 % ) and headache ( 6 % ) , but these were transient and mild in intensity . Serious adverse events and adverse events leading to discontinuation of the study drug were not reported . CONCLUSIONS Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI . Of interest , erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg", "Sildenafil ( Viagra , UK-92,480 ) is a novel oral agent under development for the treatment of penile erectile dysfunction . Erection is dependent on nitric oxide and its second messenger , cyclic guanosine monophosphate ( cGMP ) . However , the relative importance of phosphodiesterase ( PDE ) isozymes is not clear . We have identified both cGMP- and cyclic adenosine monophosphate-specific phosphodiesterases ( PDEs ) in human corpora cavernosa in vitro . The main PDE activity in this tissue was due to PDE5 , with PDE2 and 3 also identified . Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In human volunteers , we have shown sildenafil to have suitable pharmacokinetic and pharmacodynamic properties ( rapid absorption , relatively short half-life , no significant effect on heart rate and blood pressure ) for an oral agent to be taken , as required , prior to sexual activity . Moreover , in a clinical study of 12 patients with erectile dysfunction without an established organic cause , we have shown sildenafil to enhance the erectile response ( duration and rigidity of erection ) to visual sexual stimulation , thus highlighting the important role of PDE5 in human penile erection . Sildenafil holds promise as a new effective oral treatment for penile erectile dysfunction", "OBJECTIVES To assess the efficacy of intraurethral prostagl and in E1 ( alprostadil , MUSE ) in treating erectile dysfunction in patients with spinal cord injury ( SCI ) . METHODS Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction . All patients were at least 1 year after injury , and all had previously used intracavernosal injections successfully ( Schramek 's grade 5 erection ) . The intraurethral drug was administered in the office , in the presence of a physician , with monitoring of blood pressure . If effective , the patient was then able to use MUSE at home . The first 3 patients underwent gradual dose escalation starting with 125 microg , without the use of a constriction ring . Because of hypotension , the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg . The quality of the erection was compared with that achieved with intracavernosal injections using Schramek 's grading . RESULTS The dose escalation ( titration ) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response . Transient hypotension was noted in these first 3 patients in whom the constricting b and was not used . The highest dose of MUSE ( 1000 microg ) was , therefore , used in the remaining 12 patients , with the constriction b and . The quality of the erection varied and appeared to be less rigid in all patients ( 12 patients with grade 1 to 3 ; 3 patients with grade 4 ) than that noted with intracavernosal injection therapy ( 1 5 patients with grade 5 ) . There was no incidence of priapism . The 3 patients with grade 4 erections tried the MUSE at home . All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy . CONCLUSIONS MUSE appears to be somewhat effective in creating erections ; however , these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction . It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension . Its ultimate use depends on the patient 's level of satisfaction with the quality of the erection compared with intracavernosal injections", "A total of 66 spinal cord injury patients with erectile dysfunction entered a protocol of penile intracavernous pharmacotherapy with papaverine hydrochloride ( 30 mg . per ml . ) or a combination of papaverine ( 25 mg . per ml . ) and phentolamine mesylate ( 0.83 mg . per ml . ) in an attempt to restore erectile function . Of the patients 52 completed the protocol and all achieved transient functional penile erections after administration of the drug . Of the 52 responders 71 per cent currently practice self-injection as a method to restore erectile function . Sustained erections that required irrigation of the cavernous bodies with alpha-adrenergic agents developed in 4 patients and 1 suffered localized intracorporeal in duration . If the long-term followup shows that complications remain relatively minor , undoubtedly vasoactive intracavernous pharmacotherapy will have a major role in the restoration of erectile function in the motivated man with spinal cord injury . However , in view of the unknown long-term effects and potential dangers of this approach it is important that patients adhere to a strict drug injection protocol under the supervision of qualified urologists who are familiar with the potential risks and complications", "BACKGROUND Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [ corrected ] in the corpus cavernosum and therefore increases the penile response to sexual stimulation . We evaluated the efficacy and safety of sildenafil , administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic , psychogenic , and mixed causes . METHODS In a 24-week dose-response study , 532 men were treated with oral sildenafil ( 25 , 50 , or 100 mg ) or placebo . In a 12-week , flexible dose-escalation study , 329 different men were treated with sildenafil or placebo , with dose escalation to 100 mg based on efficacy and tolerance . After this dose-escalation study , 225 of the 329 men entered a 32-week , open-label extension study . We assessed efficacy according to the International Index of Erectile Function , a patient log , and a global-efficacy question . RESULTS In the dose-response study , increasing doses of sildenafil were associated with improved erectile function ( P values for increases in scores for questions about achieving and maintaining erections were sildenafil , the mean score for the question about achieving erections was 100 percent higher after treatment than at base line ( 4.0 vs. 2.0 of a possible score of 5 ) . In the last four weeks of treatment in the dose-escalation study , 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil , as compared with 22 percent for those receiving placebo ( P mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo ( P Headache , flushing , and dyspepsia were the most common adverse effects in the dose-escalation study , occurring in 6 percent to 18 percent of the men . Ninety-two percent of the men completed the 32-week extension study . CONCLUSIONS Oral sildenafil is an effective , well-tolerated treatment for men with erectile dysfunction", "To evaluate the efficacy of sildenafil in the treatment of neurogenic erectile dysfunction ( ED ) secondary to upper motor neuron ( UMN ) and lower motor neuron ( LMN ) spinal cord injury ( SCI ) . After taking consents 105 patients suffering from ED were enrolled in this prospect i ve study . Seventy-two patients had signs and symptoms of UMN and 33 patients had signs and symptoms of LMN or mixed ( UMN and LMN ) spinal cord injuries . The patients took 50 - 100 mg sildenafil or placebo tablet at least 45 min before sexual intercourse . Based on a IIEF question naire , success in achieving erection adequate for sexual intercourse was compared between sildenafil and placebo groups in UMN and non-UMN spinal cord injuries . In patients with UMN disease , sildenafil was effective in 82 % of patients and its efficacy was statistically higher than placebo ( 82 vs. 25 % , p favourable response to sildenafil that was not statistically different from placebo . Sildenafil seems more effective in the treatment of neurogenic ED secondary to UMN spinal cord injury compared with that secondary to LMN injury . Actually , its efficacy on LMN injuries does not seem different from placebo and administration of this treatment may not be effective in spinal cord injury which has caused LMN symptoms" ]

[ "Background In uncemented total hip arthroplasty with hydroxyapatite coating , early weight bearing is frequently practice d but there is still not much evidence to support this recommendation . Method In a prospect i ve r and omized study we evaluated the effect of partial and full weight bearing after cementless total hip arthroplasty ( ABG ; Stryker-Howmedica ) using radiostereometric analysis ( RSA ) . Between February 1996 and February 2000 , 43 consecutive patients ( mean age 53 ( 41–63 ) years , 23 women ) with hip osteoarthrosis received an uncemented and hydroxyapatite-coated prosthesis with an anteverted stem . All patients were operated in a st and ardized way by three experienced surgeons and they were r and omized to partial ( P ) or full ( F ) weight bearing during the first 6 weeks after surgery . The patients in the partial weight bearing group were equipped with a pressuresensitive insole signaling when their load exceeded the prescribed weight limit . Results At 3-month follow-up , the mean proximal (+)/ distal ( - ) migration of the stem was -0.14 mm ( -1.93– 0.11 ) in group P and -0.31 mm ( -4.30–0.16 ) in group F ( p = 0.6 ) . At 1-year follow-up , the mean migration was –0.17 mm ( -2.18–0.21 ) and -0.28 mm ( -4.31–0.11 ) , respectively ( p = 0.9 ) . There was no significant difference in stem rotations either ( p ) . The cup translations , rotations , and femoral head penetration were similar in the two groups ( p adverse effect of full weight bearing immediately after operation , which justifies use of this regimen after uncemented total hip arthroplasty of the ABG type", "We performed this investigation to determine the possible migration starting immediately after surgery and the effect of different weightbearing regimens on the migration pattern of an uncemented hip stem ( CLS ) . Stem migration was determined with radiostereometry analysis with baseline when the patients still were anesthetized . Subsequent examinations were done up to 1 year . Twenty-nine patients ( mean age , 55 years ; range , 26 - 63 years ) were r and omized to either unrestricted weightbearing combined with intensive physiotherapy from the first day after surgery or to partial weightbearing and a conservative training regimen for the first 3 months after surgery . At 1 week , subsidence was −0.03 mm in the unrestricted weightbearing group and 0.01 mm in the partial weightbearing group . At 1 year , subsidence was 1.01 mm in the unrestricted weightbearing group and 0.51 mm in the partial weightbearing group . One patient in the unrestricted weightbearing group had revision surgery because of aseptic loosening at 1.5 years after surgery . The CLS stem did not have any migration from the end the surgery until 1 week , but there was small migration from 1 week to 3 months after which the stem remained stable . The degree of early weightbearing did not affect the migration pattern . Level of Evidence : Level I , therapeutic study ( r and omized study ) . See the Guidelines for Authors for a complete description of levels of evidence", "Abstract . In a prospect i ve study of cementless total hip arthroplasty , 19 hips in 17 patients ( Group A ) were allowed full weight-bearing immediately after the operation while 18 hips in 16 patients ( Group B ) were first allowed weight-bearing after 6 weeks . Patients were matched for sex , age at surgery , height , weight , and follow-up period and there were no significant differences in hip scores between the two groups . Rehabilitation to gain walking ability with a cane lasted 5.8 days for Group A and 44.8 days for Group B ( P=0.0001 ) . The hospital stay after surgery was 30.1 days for Group A and 46.7 days for Group B ( P=0.006 ) . All patients showed bone ingrowth radiographically . There were no complications in either group . Résumé . Dans une étude prospect i ve d'arthroplastie totale de la hanche non-cimentée , z 17 malades ( 19 hanches ) ( Groupe A ) ont eu l'autorisation de pratiquer un appui complet immédiatement après l'intervention t and is que 16 malades ( 18 hanches ) ( Groupe B ) l'ont fait après 6 semaines . Les malades ont été appariés en regard du sexe , de l'âge à la chirurgie , de la taille , du poids , et de la durée du suivi . Il n'y avait pas de différence significative en ce qui concerne les scores du fonctionnement de la hanche entre les deux groupes . La durée de rééducation nécessaire pour obtenir la capacité de marche à l'aide d'une canne était de 5,8 jours pour le Groupe A et de 44,8 jours pour Groupe B ( P=0.0001 ) . La durée de séjour à l'hôpital après l'intervention était de 30,1 jours pour le Groupe A et de 46,7 jours pour le Groupe B ( P=0.006 ) . Nous avons constaté chez tous les patients une fixation osseuse à la radiographie . Il n'y avait aucune complication dans les deux groupes", " The vertical migration of four configurations of a proximal femoral prosthesis , followed for up to nine years , was measured on st and ard radiographs . The same implant was used without cement ( group 1 ) and with cement ( group 2 ) . The migration of both groups was linear from six months onwards . The mean migration rate and the incidence of late aseptic loosening were both greater in group 1 . Survival analysis of the two groups , however , showed no statistically significant difference . In both groups , hips later destined for revision migrated more rapidly from the initial postoperative period onwards , than did the remainder . A threshold migration of 1.2 mm/year during the first two years after implantation detected hips likely to fail with a specificity of 86 % and a sensitivity of 78 % . This ' migration test ' was applied to the results in two further groups of patients in which a modified femoral prosthesis had been implanted without hydroxyapatite coating ( group 3 ) and with hydroxyapatite coating ( group 4 ) . The test distinguished between the four groups and suggested that at least two fixation procedures should be ab and oned . We conclude that vertical migration measured on st and ard radiographs in the first two years after implantation can be used to predict late aseptic loosening . New prosthetic configurations should be evaluated by migration measurements before their general release . Our observations support the view that one cause of late aseptic loosening is imperfect initial fixation", "Background and Aims : The effectiveness of partial weightbearing after hip surgery has been question ed as well as the need of intensive physiotherapy . Material and Methods : 36 patients ( average age 54.4 , 19 women ) operated with uncemented hip arthroplasty were r and omized either to unrestricted weightbearing ( UWB ) combined with intensive physiotherapy or to partial weightbearing ( PWB ) for 3 months combined with a short self-training program . The load during walking and the muscle strength ( MS ) in abduction was measured preoperative and subsequent up to 12 months . Results : The average peak load on the operated leg at one week was 39.0 kg for the UWB and 25.8 for the PWB group ( P = 0.009 ) while at three months 70.0 and 31.7 ( P = 0.001 ) respectively . At 6 and 12 months there were no differences between the groups . The muscle strength increased in both groups up to six months but there were no differences between the groups . Conclusions : Even though patients applied more load than the recommended 15 kg most patients were able to comply with partial weightbearing fairly well . The effect of intensive physiotherapy on the muscle strength after hip arthroplasty is question able", "& NA ; There is considerable variation between centres in the use of forearm crutches in the rehabilitation of patients with total hip arthroplasty who are capable of full weight bearing . This study aim ed to compare the gait of patients with total hip arthroplasty walking with and without crutches . The gait analysis in 19 patients included the assessment of kinematics , kinetics and the kinesiological electromyographic activity of lower limb and trunk muscles . With the forearm crutches patients walked with a reduced cadence , a longer stride length and more symmetrically ( P activity of the gluteus medius , vastus medialis and lateralis , and erector spinae muscles of the affected and of the vastus medialis muscle of the unaffected side decreased significantly ( P subjects displayed an abnormal activation pattern of the affected hip abductor when walking with forearm crutches , characterized by a second burst during swing ( n = 5 ) or a tonic pattern ( n = 2 ) . It is concluded that the use of forearm crutches result ed in a symmetrical gait pattern . The reduced activity of relevant pelvi‐trochanteric muscles and the disturbed activation pattern of the affected hip abductor when walking with crutches might indicate that patients should walk unaided as soon as possible to provide a more efficient muscular training under dynamic conditions . Gang mit und ohne Unterarmkrücken bei Patienten mit Hüft‐TEP Es gibt erhebliche Unterschiede zwischen den Zentren bei der Verwendung von Unterarmkrücken bei der Rehabilitation von Patienten mit Hüft‐TEP , die voll belastbar sind . Diese Studie hat das Ziel , den Gang von Patienten mit Hüft‐TEP , die mit und ohne Krücken gehen , zu vergleichen . Die Gangauswertung bei 19 Patienten umfa&bgr;t die Beurteilung der Kinematik , Kinetik und der kinesiologischen elektromyeolographischen Aktivität der Muskeln von Rumpf und unteren Extremitäten . Mit den Unterarmkrücken gingen die Patienten mit einem verlangsamten Rhythmus , einer grö&bgr;eren Schrittlänge und symmetrischer ( P Aktivität der Mm gluteus , vastus medialis und laterialis sowie erector spinae der betroffenen und des M. vastus medialis der nichtbetroffenen Seite nahmen erheblich ab ( P Patienten beim Gehen mit Unterarmkrücken ein abnormes Aktivierungsmuster des betroffenen Hüftabduktors , das sich in einem zweiten Impuls beim Schwung ( n = 5 ) oder einem tonischen Muster ( n = 2 ) äu&bgr;erte . Schlu&bgr;folgerung : Die Verwendung von Unterarmstützen führte zu einem symmetrischen Gangmuster . Die verringerte Aktivität von relevanten Muskeln von Becken und Trochanter und das gestörte Aktivierungsmuster des betroffenen Hüftabduktors beim Gehen mit Krücken lassen ein alsbaldiges Gehen ohne Hilfsmittel als sinnvoll erscheinen , um ein effizienteres Muskeltraining unter dynamischen Bedingungen zu ermöglichen . Déambulation avec et sans Béquilles après une Arthroplastie Totale de Hanche Il existe une variation considérable selon les centres concernant l'utilisation de béquilles pour la rééducation des patients ayant bénéficié d'une arthroplastie totale de hanche capables de supporter totalement leur poids . Cette étude était destinée à comparer la déambulation des patients après une arthroplastie totale de hanche marchant avec ou sans béquilles . L'analyse de la déambulation effectuée chez 19 patients incluait une évaluation cinématique , cinétique et une étude de l'activité électromyographique kinésiologique des muscles des membres inférieures et des muscles du tronc . Avec des béquilles , les patients ont marché plus lentement , à plus petits pas et plus symétriquement ( P des muscles moyen fessier , vastes intérne et externe du membre inférieur et celle des muscles spinaux du côté atteint ont diminué significativement ( P activation anormale des abducteurs de hanche du côté atteint lors de la déambulation avec béquilles , se caractérisant par une deuxième salve d'activité électrique lors du balancement ( n = 5 ) ou un tracé tonique ( n = 2 ) . Conclusion : L'utilisation de béquilles a permis une déambulation symétrique . Toutefois , pour une rééducation musculaire plus efficace , en conditions dynamiques , il est recomm and é de recourir le plus rapidement possible après l'intervention à une déambulation sans aide en raison de la diminution de l'activité des muscles pelvi‐trochantériens concernés et de l'activation paradoxale des abducteurs de hanche du côté atteint lors de la déambulation avec béquilles . Deambulación con o sin Muletas de Apoyo en El Antebrazo en Pacientes Sometidos a Artroplastia de Cadera Completa Existe una gran variabilidad entre los centros en cuanto al uso de muletas de apoyo en el antebrazo en la rehabilitación de los pacientes sometidos a artoplastia de cadera completa que pueden soportar todo el peso . El objetivo de este estudio fue comparar la marcha de los pacientes con artoplastia de cadera completa que caminaban con y sin muletas . El análisis de la marcha en 19 pacientes incluyó la valoración de la cinemática , de la cinética y de la actividad cinesiológica en el electromiograma de los músculos de las extremidades inferiores y del tronco . Con las muletas de apoyo en el antebrazo , los pacientes caminaron con una cadencia menor , con una mayor zancada y de forma más simétrica ( P la actividad de los músculos glúteo medio , vasto medial y lateral y erector de la espina dorsal del lado afectado , y del músculo vasto medial contralateral disminuyó de forma significativa ( P de apoyo en el antebrazo , que se caracterizó por una segunda descarga durante el balanceo ( n = 5 ) o un patrón tónico ( n = 2 ) . Conclusión : el uso de muletas de apoyo en el antebrazo produjo un patrón de la marcha simétrico . La disminución de la actividad de los principales músculos de la pelvis y del trocánter y la alteración del patrón de activación del abductor de la cadera afectada producida al caminar con muletas hacen recomendable la deambulación sin ayuda tan pronto como sea posible para conseguir un entrenamiento muscular más eficaz en condiciones dinámicas . International Journal of Rehabilitation Research", "Forty-two patients ( younger than 65 years ) with osteoarthritis were operated on with an uncemented CLS stem and r and omized to early unrestricted weight bearing combined with intensive physiotherapy or to partial weight bearing combined with self-training . Radiostereometric analysis showed 1.2 ( + 0.11 to -6.76 ) mm subsidence of the stem at 24 months in both groups . There was no significant difference in the migration pattern between the unrestricted and partial weight bearing groups . Actual loading on the operated leg , measured with the F-scan system , did not influence the migration of the stem . There was a strong correlation between the average subsidence at 3 and 24 months ( r = 0.96 ) . Early full weight bearing and active rehabilitation can be used for the uncemented CLS stem without increased risk of early loosening", "OBJECTIVE To investigate the effects of a late-phase exercise program for patients who underwent total hip arthroplasty ( THA ) 4 to 12 months earlier . DESIGN A single-blind , r and omized controlled trial . SETTING Exercises were performed in subjects ' homes . Exercise instruction and measurements taken before and after the trial were performed in an outpatient research and treatment center . PARTICIPANTS Convenience sample of 34 adults 4 to 12 months post-THA r and omly allocated to experimental or control groups . Twenty-eight subjects completed the study . INTERVENTION An 8-week , hip-exercise intervention , during which the control group received basic isometric and active range of motion exercises ; the experimental group received strength and postural stability exercises . MAIN OUTCOME MEASURES Score on the 12-Item Hip Question naire ; fear of falling ; hip flexor , extensor , abductor , and knee extensor muscle torque ; and postural stability in single stance . RESULTS There was a statistically significant improvement in all measures of self-perceived function , muscle strength ( hip flexors , 24.4 % ; hip extensors , 47.8 % ; hip abductors , 41.2 % ; knee extensors , 23.4 % ) , and postural stability ( 36.8 % ) in the experimental group and no significant change in the control group . Neither group had statistically significant changes in fear of falling measures . CONCLUSIONS An exercise program emphasizing weight bearing and postural stability significantly improved muscle strength , postural stability , and self-perceived function in patients 4 to 12 months after THA", "CONTEXT Inpatient rehabilitation after elective hip and knee arthroplasty is often necessary for patients who can not function at home soon after surgery , but how soon after surgery inpatient rehabilitation can be initiated has not been studied . OBJECTIVE To test the hypothesis that high-risk patients undergoing elective hip and knee arthroplasty would incur less total cost and experience more rapid functional improvement if inpatient rehabilitation began on postoperative day 3 rather than day 7 , without adverse consequences to the patients . DESIGN R and omized controlled trial conducted from 1994 to 1996 . SETTING Tertiary care center . PARTICIPANTS A total of 86 patients undergoing elective hip or knee arthroplasty and who met the following criteria for being high risk : 70 years of age or older and living alone , 70 years of age or older with 2 or more comorbid conditions , or any age with 3 or more comorbid conditions . Of the 86 patients , 71 completed the study . INTERVENTIONS R and om assignment to begin inpatient rehabilitation on postoperative day 3 vs postoperative day 7 . MAIN OUTCOME MEASURES Total length of stay and cost from orthopedic and rehabilitation hospital admissions , functional performance in hospitals using a subset of the functional independence measure , and 4-month follow-up assessment using the R AND 36-item health survey I and the functional status index . RESULTS Patients who completed the study and began inpatient rehabilitation on postoperative day 3 exhibited shorter mean ( + /-SD ) total length of stay ( 11.7+/-2.3 days vs 14.5+/-1.9 , P mean ( + /-SD ) total cost ( $ 25891+/-$3648 vs $ 27762+/-$3626 , P attainment of short-term functional milestones between days 6 and 10 ( 36.2+/-14.4 m ambulated vs 21.4+/-13.3 m , P transfer functional independence measure score vs 4.3+/-0.7 , P outcome at 4-month follow-up . CONCLUSION These data showed that high-risk individuals were able to tolerate early intensive rehabilitation , and this intervention yielded faster attainment of short-term functional milestones in fewer days using less total cost", "A prospect i ve study was conducted to quantitatively measure the relative muscle torque strengths in 20 consecutive women with unilateral osteoarthritic hips and 20 consecutive men with unilateral osteonecrotic hips before and after primary cementless total hip arthroplasty . Maximal isometric torque strengths in the muscles of flexion , extension , and abduction around the hip joint were measured preoperatively and postoperatively at six months and one year , using a Cybex 340 dynamometer . The results showed improved muscle function after total hip arthroplasty in both diseased and healthy hips . In the diseased hips , all muscle groups improved significantly , from 150 to 250 % of the preoperative levels , at six months and one year postoperatively , except in the osteoarthritic women , in whom the improvement at six months was minimal . Preoperatively , all muscle groups in the diseased hips were weaker than those in the uninvolved hips , especially in the osteonecrotic men ( 51 - 79 % of healthy side ) . In both groups , however , the torques strengths of the diseased hips had not caught up to the healthy hips in the one-year follow-up period ( 84 - 89 % in the osteonecrotic male group , and 79 - 81 % in the osteoarthritic female group ) . The authors recommended that muscle strengthening exercises for the hip should be continued for at least one year , and perhaps longer , after total hip arthroplasty", "BACKGROUND Few guidelines are available whether early weight-bearing after an uncemented total hip arthroplasty ( THA ) can be recommended or not . Stability and ingrowth may be jeopardized by immediate loading of the implant while functional recovery may be promoted and periprosthetic demineralization reduced . PATIENTS AND METHODS We did a prospect i ve study of 20 patients who were operated on with a hydroxyapatite-coated ( HA ) , uncemented total hip arthroplasty with a tapered stem because of unilateral arthrosis , and r and omized the patients to the immediate ( I ) or late ( L ) weight-bearing ( after 3 months ) group . The shoe on the operated side was equipped with an auditory device signaling when the patient placed a load on the extremity . The clinical assessment was done with the Harris hip score at the time of the operation and after 12 and 24 months . Radiographs and dual-energy x-ray absorptiometry ( DEXA ) were evaluated for migration , femoral remodeling and bone mineral density ( BMD ) after 3 , 6 , 12 and 24 months . Tc-scintigraphy was done after 6 , 12 and 24 months . RESULTS Postoperatively , the Harris hip score showed no group difference . After 3 months , we noted a large reduction in BMD around the stem prosthesis . This was most marked in the proximal regions and the bone loss was significantly larger in zone 1 , 4 and 5 in the L group . Distally , the BMD normalized with time , but the loss of bone persisted in the proximal zones after 24 months . An initial increase in the scintigraphic uptake ratio in all zones in both groups declined with time , but it was still increased on the operated side after 24 months . Several radiographic signs of bone remodeling were seen , but the patterns were similar in both groups . INTERPRETATION We found no adverse effect of immediate weight bearing with this prosthesis" ]

[ "BACKGROUND AND PURPOSE Although the efficacy of anticoagulant therapy for primary prevention of stroke in patients with nonvalvular atrial fibrillation ( NVAF ) has been established , efficacy of antiplatelet therapy for low-risk patients is disputable in Japanese patients because of the frequent hemorrhagic complications . We examined the efficacy and safety of aspirin therapy in Japanese patients with NVAF in a prospect i ve r and omized multicenter trial . METHODS Patients with NVAF were r and omized to an aspirin group ( aspirin at 150 to 200 mg per day ) or a control group without antiplatelet or anticoagulant therapy . Primary end points included cardiovascular death , symptomatic brain infa rct ion , or transient ischemic attack . RESULTS A total of 426 patients were r and omized to aspirin group and 445 to no treatment . The trial was stopped earlier because there were 27 primary end point events ( 3.1 % per year ; 95 % CI , 2.1 % to 4.6 % per year ) in the aspirin group versus 23 ( 2.4 % per year ; 95 % CI , 1.5 % to 3.5 % per year ) in the control group , suggesting a low possibility of superiority of the aspirin treatment for prevention of the primary end point . In addition , treatment with aspirin caused a marginally increased risk of major bleeding ( 7 patients ; 1.6 % ) compared with the control group ( 2 patients ; 0.4 % ; Fisher exact test P=0.101 ) . CONCLUSIONS For prevention of stroke in patients with NVAF , aspirin at 150 to 200 mg per day does not seem to be either effective or safe . Further prospect i ve studies are needed to determine the best preventive therapy for cerebrovascular events in Japanese patients with NVAF", "BACKGROUND To test the use of three lead monitoring as a screening tool for atrial fibrillation ( AF ) in general practice . AF is responsible for up to a quarter of all strokes and is often asymptomatic until a stroke occurs . METHODS 26 r and omly selected general practice s identified 80 r and omly selected patients aged 70 or older from their data base and excluded those known to have AF , those with clinical issues or who had not attended for three years . Up to 40 eligible patients / practice were invited to attend for screening . A 2min three-lead ECG was recorded and collected central ly for expert cardiology assessment . Risk factor data was gathered . OUTCOMES ( i ) point prevalence of AF , ( ii ) proportion of ECG tracings which were adequate for interpretation , ( iii ) uptake rate by patients and ( iv ) acceptability of the screening process to patients and staff ( reported separately ) . RESULTS Of 1447 current patients , 1003 were eligible for inclusion , 639 ( 64 % ) agreed to take part in screening and 566 ( 56 % ) completed screening . The point prevalence rate for AF was 10.3%-2.1 % new cases ( 12 of 566 who were screened ) and 9.5 % existing cases ( 137 of 1447 eligible patients ) . Only four of 570 ( 0.7 % ) screening visits did not record a usable ECG and 11 ( 2.6 % ) three lead ECGs required a clarifying 12 lead ECG . CONCLUSIONS Three lead screening for AF is feasible , effective and offers an alternative to pulse taking or 12 lead ECGs . The availability of this technology may facilitate more effective screening , leading to reduced stroke incidence", "Objectives To assess whether screening improves the detection of atrial fibrillation ( cluster r and omisation ) and to compare systematic and opportunistic screening . Design Multicentred cluster r and omised controlled trial , with subsidiary trial embedded within the intervention arm . Setting 50 primary care centres in Engl and , with further individual r and omisation of patients in the intervention practice s. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practice s. Interventions Patients in intervention practice s were r and omly allocated to systematic screening ( invitation for electrocardiography ) or opportunistic screening ( pulse taking and invitation for electrocardiography if the pulse was irregular ) . Screening took place over 12 months in each practice from October 2001 to February 2003 . No active screening took place in control practice s. Main outcome measure Newly identified atrial fibrillation . Results The detection rate of new cases of atrial fibrillation was 1.63 % a year in the intervention practice s and 1.04 % in control practice s ( difference 0.59 % , 95 % confidence interval 0.20 % to 0.98 % ) . Systematic and opportunistic screening detected similar numbers of new cases ( 1.62 % v 1.64 % , difference 0.02 % , −0.5 % to 0.5 % ) . Conclusion Active screening for atrial fibrillation detects additional cases over current practice . The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography . Trial registration Current Controlled Trials IS RCT N19633732", "INTRODUCTION AND OBJECTIVES Atrial fibrillation constitutes a serious public health problem because it can lead to complications . Thus , the management of this arrhythmia must include not only its treatment , but antithrombotic therapy as well . The main goal is to determine the proportion of cases of undiagnosed atrial fibrillation and the proportion of patients not being treated with oral anticoagulants . METHODS A multicenter , population -based , retrospective , cross-sectional , observational study . In all , 1043 participants over 60 years of age were r and omly selected to undergo an electrocardiogram in a prearranged appointment . Demographic data , CHA2DS2-VASc and HAS-BLED scores , international normalized ratio results , and reasons for not receiving oral anticoagulant therapy were recorded . RESULTS The overall prevalence of atrial fibrillation was 10.9 % ( 95 % confidence interval , 9.1%-12.8 % ) , 20.1 % of which had not been diagnosed previously . In the group with known atrial fibrillation , 23.5 % of those with CHA2DS2-VASc≥2 were not receiving oral anticoagulant therapy , and 47.9 % had a HAS-BLED score≥3 . The odds ratio for not being treated with oral anticoagulation was 2.04 ( 95 % confidence interval , 1.11 - 3.77 ) for women , 1.10 ( 95 % confidence interval , 1.05 - 1.15 ) for more advanced age at diagnosis , and 8.61 ( 95 % confidence interval 2.38 - 31.0 ) for a CHA2DS2-VASc score ( 15.2 % ) was the main reason for not receiving oral anticoagulant therapy . CONCLUSIONS The prevalence of previously undiagnosed atrial fibrillation in individuals over 60 years of age is 20.1 % , and 23.5 % of those who have been diagnosed receive no treatment with oral anticoagulants", "AIM Atrial fibrillation ( AF ) is associated with high morbidity and mortality . Early diagnosis is likely to improve therapy and prognosis . The study objective was to evaluate the usefulness of a programme for early diagnosis of AF in patients from an urban primary care centre . METHODS AND RESULTS Participants were recruited from a r and omized sample of patients not diagnosed with AF but having relevant risk factors : age ≥ 65 years , ischaemic and /or valvular heart disease , congestive heart failure , hypertension , and /or diabetes . Patients were r and omly assigned to the intervention group ( IG ) or control group ( CG ) . The intervention included ( i ) initial visit with clinical history , electrocardiogram , and instruction about pulse palpation and warning signs and ( ii ) electrocardiogram every 6 months during a 2-year follow-up . The main endpoint of the study was the proportion of new cases diagnosed at 6 months . Secondary endpoints were number of new AF diagnoses and complications associated with the arrhythmia in both groups . A total of 928 patients were included ( 463 IG and 465 CG ) . At 6 months , AF was diagnosed in 8 IG patients and 1 CG patient ( 1.7 vs. 0.2 % , respectively , P = 0.018 ) . After 2 years of follow-up , 11 IG patients and 6 CG patients had newly diagnosed AF ( 2.5 vs. 1.3 % , respectively , P = 0.132 ) . Time to first diagnosis of AF was shorter in IG patients [ median ( inter-quartile range ) : 7 ( 192 ) days vs. 227 ( 188.5 ) days in CG , P = 0.029 ] . CONCLUSION The simple screening proposed could be useful for the early detection of AF in primary care", "BACKGROUND R and omized trials have shown a beneficial effect of anticoagulation with warfarin to prevent stroke in atrial fibrillation . It is not known whether the same effect will be obtained in actual practice . The authors conducted a prospect i ve observational study to evaluate the effect of preventive anticoagulation in patients with atrial fibrillation in 2 practice setting s in Montreal . METHODS Of the 1725 out patients screened between October 1990 and September 1993 at a community hospital and a university-affiliated hospital , 221 with documented atrial fibrillation were enrolled and followed up for a mean of 27 months . Most ( 75 % ) of the patients excluded did not meet the inclusion criteria ( because of , for example , an artificial heart valve , mitral stenosis , cardiac transplantation or transient atrial fibrillation ) ; the remainder had not completed enrollment before the end of the study . Following the baseline visit , patients were interviewed by telephone every 6 months , and reported events were confirmed through review of the patients ' charts . Hazards for stroke and for stroke and transient ischemic attack ( TIA ) combined were calculated for each of 4 treatment groups : ASA , warfarin , blended treatment and no treatment , based on the type of anticoagulation therapy patients received during the entire observation period . The blended-treatment group consisted of patients who started on one active therapy and switched to the other or who switched treatments more than once . Corresponding rate ratios ( RRs ) and 95 % confidence intervals ( CIs ) were calculated with reference to the no-treatment group . Cox proportional hazards analysis was used to adjust for differences in patient characteristics . The rates of bleeding episodes were also analysed . RESULTS On average , the study patients were older ( 71.6 [ st and ard deviation 9.3 ] years ) and had a higher prevalence of underlying heart disease ( 52.0 % ) than those in the r and omized trials . Nineteen patients had a first stroke : 4 in the ASA group , 4 in the warfarin group , 4 in the blended-treatment group and 7 in the no-treatment group , for rates of 5.2 , 1.8 , 5.3 and 5.9 per 100 person-years , respectively . Only warfarin was associated with a significantly lower risk of stroke compared with no anticoagulant therapy ( RR 0.31 , 95 % CI 0.09 - 1.00 ) . A similar protective effect of warfarin was found for stroke and TIA combined ( 2.3 v. 6.7 per 100 person-years ; RR 0.34 , 95 % CI 0.12 - 0.99 ) ; the effect of ASA and blended treatment was not significantly different from no treatment . The rate per 100 person-years of any bleeding was not significantly higher for any treatment group ( ASA 2.5 , warfarin 3.4 and blended treatment 3.5 ) compared with the no-treatment group ( 1.9 ) . Patients receiving warfarin had a significantly greater risk of any bleeding event than patients not receiving anticoagulant therapy ( RR 1.79 , 95 % CI 1.07 - 3.00 ) . INTERPRETATION The relative effect of anticoagulant therapy with warfarin in preventing stroke in these practice setting s was equivalent to that in the r and omized trials , although these patients were older and sicker . This preventive treatment is likely to confer additional benefit as it is more widely prescribed", "Background and Purpose — Stroke risk increases with age in patients who have nonvalvular atrial fibrillation . It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age . The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants ( OAC ) and antiplatelet ( AP ) therapy ( including acetylsalicylic acid and triflusal ) on ischemic stroke , serious bleeding , and vascular events in patients with atrial fibrillation . Methods — This is an analysis of the Atrial Fibrillation Investigators data base , which contains patient level- data from r and omized trials of stroke prevention in atrial fibrillation . We used Cox regression models with age as a continuous variable that controlled for sex , year of r and omization , and history of cerebrovascular disease , diabetes , hypertension , and congestive heart failure . Outcomes included ischemic stroke , serious bleeding ( intracranial hemorrhage or systemic bleeding requiring hospitalization , transfusion , or surgery ) , and cardiovascular events ( ischemic stroke , myocardial infa rct ion , systemic embolism , or vascular death ) . Results — The analysis included 8932 patients and 17 685 years of observation from 12 trials . Patient age increased risk of ischemic stroke ( adjusted hazard ratio per decade increase 1.45 ; 95 % CI , 1.26 to 1.66 ) , serious bleeding ( 1.61 ; 1.47 to 1.77 ) , and cardiovascular events ( 1.43 ; 1.33 to 1.53 ) . Compared with placebo , OAC and AP significantly reduced the risk of ischemic stroke ( OAC , 0.36 ; 0.29 to 0.45 ; AP , 0.81 ; 0.72 to 0.90 ) and cardiovascular outcomes ( OAC , 0.59 ; 0.52 to 0.66 ; AP , 0.81 ; 0.75 to 0.88 ) , whereas OAC increased risk of serious bleeding ( 1.56 ; 1.03 to 2.37 ) . The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome . Compared with placebo , the relative benefit of AP for preventing ischemic stroke decreased significantly as patients aged ( P=0.01 ) . Conclusions — As patients with atrial fibrillation age , the relative efficacy of AP to prevent ischemic stroke appears to decrease , whereas it does not change for OAC . Because stroke risk increases with age , the absolute benefit of OAC increases as patients get older", "ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on", "Objective To assess the accuracy of general practitioners , practice nurses , and interpretative software in the use of different types of electrocardiogram to diagnose atrial fibrillation . Design Prospect i ve comparison with reference st and ard of assessment of electrocardiograms by two independent specialists . Setting 49 general practice s in central Engl and . Participants 2595 patients aged 65 or over screened for atrial fibrillation as part of the screening for atrial fibrillation in the elderly ( SAFE ) study ; 49 general practitioners and 49 practice nurses . Interventions All electrocardiograms were read with the Biolog interpretative software , and a r and om sample of 12 lead , limb lead , and single lead thoracic placement electrocardiograms were assessed by general practitioners and practice nurses independently of each other and of the Biolog assessment . Main outcome measures Sensitivity , specificity , and positive and negative predictive values . Results General practitioners detected 79 out of 99 cases of atrial fibrillation on a 12 lead electrocardiogram ( sensitivity 80 % , 95 % confidence interval 71 % to 87 % ) and misinterpreted 114 out of 1355 cases of sinus rhythm as atrial fibrillation ( specificity 92 % , 90 % to 93 % ) . Practice nurses detected a similar proportion of cases of atrial fibrillation ( sensitivity 77 % , 67 % to 85 % ) , but had a lower specificity ( 85 % , 83 % to 87 % ) . The interpretative software was significantly more accurate , with a specificity of 99 % , but missed 36 of 215 cases of atrial fibrillation ( sensitivity 83 % ) . Combining general practitioners ' interpretation with the interpretative software led to a sensitivity of 92 % and a specificity of 91 % . Use of limb lead or single lead thoracic placement electrocardiograms result ed in some loss of specificity . Conclusions Many primary care professionals can not accurately detect atrial fibrillation on an electrocardiogram , and interpretative software is not sufficiently accurate to circumvent this problem , even when combined with interpretation by a general practitioner . Diagnosis of atrial fibrillation in the community needs to factor in the reading of electrocardiograms by appropriately trained people", "BACKGROUND The prognostic significance of the clinical presentation of atrial fibrillation ( AF ) is poorly defined . OBJECTIVE The purpose of this study was to determine the frequency , associations , and prognostic impact of different clinical presentations of new-onset AF . METHODS One thous and patients with incident AF in Olmsted County , Minnesota , were r and omly selected ( 2000 - 2010 ) . Patients with AF that was complicated at presentation ( heart failure [ n = 71 ] , thromboembolism [ n = 24 ] ) , provoked ( n = 346 ) , or unable to determine symptoms ( n = 83 ) were excluded . In the remaining patients , characteristics and prognosis associated with different types of symptoms were examined . RESULTS Among 476 patients , 193 had typical ( palpitations ) , 122 had atypical ( other non-palpitation symptoms ) , and 161 had asymptomatic AF presentation . Patients with typical presentation had lower CHA2DS2-VASc scores ( mean 2.3 ± 2 ) compared to atypical and asymptomatic presentation ( mean 3.2 ± 1.8 and 3.3 ± 1.9 , respectively ; P cerebrovascular events and 149 deaths ( n = 49 cardiovascular ) were documented over median 5.6 and 6.0 years , respectively . Atypical and asymptomatic AF conferred higher risks of cerebrovascular events compared to typical AF after adjustment for CHA2DS2-VASc score and age ( hazard ratio [ HR ] 3.51 , 95 % confidence interval [ CI ] 1.65 - 7.48 , and HR 2.70 , 95 % CI 1.29 - 5.66 , respectively ) , and associations remained statistically significant after further adjustments including comorbidities and warfarin use . Asymptomatic AF was associated with an increased risk of cardiovascular ( HR 3.12 , 95 % CI 1.50 - 6.45 ) and all-cause mortality ( HR 2.96 , 95 % CI 1.89 - 4.64 ) compared to typical AF after adjustment for CHA2DS2-VASc score and age . CONCLUSION The type of clinical presentation may have important implication s for the prognosis of new-onset AF in the community", "The present study was undertaken to reassess prospect ively the immediate and long-term results of direct-current electrical cardioversion in chronic atrial fibrillation or atrial flutter , and to determine factors predicting clinical outcome of the arrhythmia after direct-current cardioversion . Two-hundred forty-six patients underwent direct-current electrical cardioversion and were followed during a mean of 260 days . Multivariate analysis was used to identify factors predicting short- and long-term arrhythmia outcome . Cardioversion was achieved in 70 % of patients with atrial fibrillation and in 96 % of patients with atrial flutter . Stepwise logistic regression analysis revealed that arrhythmia duration ( p less than 0.001 ) , type of arrhythmia ( fibrillation vs flutter , p less than 0.02 ) and age ( p less than 0.05 ) independently influenced conversion rate . On an actuarial basis , 42 and 36 % of patients remained in sinus rhythm during 1 and 2 years , respectively . Multivariate regression analysis revealed that the type of arrhythmia ( p = 0.0008 ) , low precardioversion functional class ( p = 0.002 ) and the presence of nonrheumatic mitral valve disease ( p = 0.03 ) independently increased the length of the arrhythmia-free episode . Rheumatic heart disease shortened this period ( p = 0.03 ) . In conclusion , patients having a high probability of conversion together with a prolonged post-shock arrhythmia-free episode can be identified . This may improve the cost-benefit ratio of cardioversion", "Atrial fibrillation ( AF ) is a common arrhythmia in elderly persons and a common cause of embolic stroke . Most studies of the prevalence and correlates of AF have used selected , hospital-based population s. The Cardiovascular Health Study is a population -based , longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged > or = 65 years . AF was diagnosed in 4.8 % of women and in 6.2 % of men at the baseline examination , and prevalence was strongly associated with advanced age in women . Prevalence of AF was 9.1 % in men and women with clinical cardiovascular disease , 4.6 % in patients with evidence of sub clinical but no clinical cardiovascular disease , and only 1.6 % in subjects with neither clinical nor sub clinical cardiovascular disease . A history of congestive heart failure , valvular heart disease and stroke , echocardiographic evidence of enlarged left atrial dimension , abnormal mitral or aortic valve function , treated systemic hypertension , and advanced age were independently associated with the prevalence of AF . The low prevalence of AF in the absence of clinical and sub clinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called \" lone atrial fibrillation \" in the elderly", "The Canadian Atrial Fibrillation Anticoagulation Study was a r and omized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage . As a result of the publication of two other \" positive \" studies of similar design and objective , this study was stopped early before completion of its planned recruitment of 630 patients . There were 187 patients r and omized to warfarin and 191 to placebo . Permanent discontinuation of study medication occurred in 26 % of warfarin-treated and 23 % of placebo-treated patients . The target range of the international normalized ratio was 2 to 3 . For the warfarin-treated patients , the international normalized ratio was in the target range 43.7 % of the study days , above it 16.6 % of the study days and below it 39.6 % of the study days . Fatal or major bleeding occurred at annual rates of 2.5 % in warfarin-treated and 0.5 % in placebo-treated patients . Minor bleeding occurred in 16 % of patients receiving warfarin and 9 % receiving placebo . The primary outcome event cluster was nonlacunar stroke , non central nervous systemic embolism and fatal or intracranial hemorrhage . Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication . The annual rates of the primary outcome event cluster were 3.5 % in warfarin-treated and 5.2 % in placebo-treated patients , with a relative risk reduction of 37 % ( 95 % confidence limits , -63.5 % , 75.5 % , p = 0.17 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "INTRODUCTION Atrial fibrillation ( AF ) is an important independent risk factor for stroke and oral anticoagulation therapy provides a highly effective treatment to reduce this risk . Active screening strategies improve detection of AF in comparison with routine care ; however , whether screen-detected patients have stroke risk profiles favouring anticoagulation is unclear . Using data derived from the screening for AF in the elderly ( SAFE ) study , the aim of this article was to determine if patients with AF detected via active screening have stroke risk profiles that warrant prophylactic anticoagulation . METHODS Secondary analysis of data derived from 25 general practice s within which cohorts of 200 patients were r and omly allocated to opportunistic [ pulse and electrocardiogram ( ECG ) ] or systematic screening ( postal invitation for ECG ) . Stroke risk assessment was undertaken using baseline data extracted from medical records and CHADS2 criteria . CHADS2 scores were compared between the screening groups . RESULTS One hundred and forty-nine new cases of AF were detected , 75 via opportunistic screening and 74 via systematic screening . CHADS2 scores were ≥1 in 83 % [ 95 % confidence interval ( CI ) 72.6 - 89.6 ] of patients detected via opportunistic screening and 78 % ( 95 % CI 67.7 - 86.2 ) detected via systematic screening . There were no significant differences in stroke risk profiles of patients detected via opportunistic and systematic screenings . CONCLUSION Stroke risk profiles of patients detected via opportunistic and systematic screenings were similar . Data derived from the SAFE study suggest that active screening for AF in patients aged ≥65 years in primary care is a useful screening programme with 78 - 83 % of patients identified eligible for anticoagulation treatment according to the CHADS2 criteria", "BACKGROUND Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation . However , recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm . We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation . METHODS We r and omly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aim ed at rate control or rhythm control . Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication . Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs . The end point was a composite of death from cardiovascular causes , heart failure , thromboembolic complications , bleeding , implantation of a pacemaker , and severe adverse effects of drugs . RESULTS After a mean ( + /-SD ) of 2.3+/-0.6 years , 39 percent of the 266 patients in the rhythm-control group had sinus rhythm , as compared with 10 percent of the 256 patients in the rate-control group . The primary end point occurred in 44 patients ( 17.2 percent ) in the rate-control group and in 60 ( 22.6 percent ) in the rhythm-control group . The 90 percent ( two-sided ) upper boundary of the absolute difference in the primary end point was 0.4 percent ( the prespecified criterion for noninferiority was 10 percent or less ) . The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups . CONCLUSIONS Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion", "BACKGROUND Rate control is often the therapy of choice for atrial fibrillation . Guidelines recommend strict rate control , but this is not based on clinical evidence . We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation . METHODS We r and omly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy ( resting heart rate The primary outcome was a composite of death from cardiovascular causes , hospitalization for heart failure , and stroke , systemic embolism , bleeding , and life-threatening arrhythmic events . The duration of follow-up was at least 2 years , with a maximum of 3 years . RESULTS The estimated cumulative incidence of the primary outcome at 3 years was 12.9 % in the lenient-control group and 14.9 % in the strict-control group , with an absolute difference with respect to the lenient-control group of -2.0 percentage points ( 90 % confidence interval , -7.6 to 3.5 ; P frequencies of the components of the primary outcome were similar in the two groups . More patients in the lenient-control group met the heart-rate target or targets ( 304 [ 97.7 % ] , vs. 203 [ 67.0 % ] in the strict-control group ; P total visits ( 75 [ median , 0 ] , vs. 684 [ median , 2 ] ; P frequencies of symptoms and adverse events were similar in the two groups . CONCLUSIONS In patients with permanent atrial fibrillation , lenient rate control is as effective as strict rate control and is easier to achieve . ( Clinical Trials.gov number , NCT00392613 .", " From November , 1985 , to June , 1988 , 1007 out patients with chronic non-rheumatic atrial fibrillation ( AF ) entered a r and omised trial ; 335 received anticoagulation with warfarin openly , and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo . Each patient was followed up for 2 years or until termination of the trial . The primary endpoint was a thromboembolic complication ( stroke , transient cerebral ischaemic attack , or embolic complications to the viscera and extremities ) . The secondary endpoint was death . The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups , which did not differ significantly . 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo . 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo . Thus , anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF", "OBJECTIVES To determine the most cost-effective method of screening for atrial fibrillation ( AF ) in the population aged 65 years and over , as well as its prevalence and incidence in this age group . Also to evaluate the relative cost-effectiveness of different methods of recording and interpreting the electrocardiogram ( ECG ) within a screening programme . DESIGN Multicentred r and omised controlled trial . Purpose fully selected general practice s were r and omly allocated to 25 intervention practice s and 25 control practice s. SETTING Fifty primary care centres across the West Midl and s , UK . PARTICIPANTS Patients aged 65 years and over . INTERVENTIONS GPs and practice nurses in the intervention practice s received education on the importance of AF detection and ECG interpretation . Patients in the intervention practice s were r and omly allocated to systematic ( n = 5000 ) or opportunistic screening ( n = 5000 ) . Prospect i ve identification of pre-existing risk factors for AF within the screened population enabled comparison between targeted screening of people at higher risk of AF and total population screening . MAIN OUTCOME MEASURES AF detection rates in systematic ally screened and opportunistically screened population s in the intervention practice s were compared with AF detection rate in 5000 patients in the control practice s. The screening period was 12 months . RESULTS Baseline prevalence of AF was 7.2 % , with a higher prevalence in males ( 7.8 % ) and patients aged 75 years and over ( 10.3 % ) . The control population demonstrated higher baseline prevalence ( 7.9 % ) than either the systematic ( 6.9 % ) or opportunistic ( 6.9 % ) intervention population . In the control population 47 new cases were detected ( incidence 1.04 % per year ) . In the opportunistic arm 243 patients without a baseline diagnosis of AF were found to have an irregular pulse , with 177 having an ECG , yielding 31 new cases ( incidence 0.69 % per year ) . A further 44 cases were detected outside the screening programme ( overall incidence 1.64 % per year ) . In the systematic arm 2357 patients had an ECG yielding 52 new cases ( incidence 1.1 % per year ) . Of these , 31 were detected by targeted screening and a further 21 by total population screening . A further 22 cases were detected outside the screening programme ( overall incidence 1.62 % per year ) . In terms of ECG interpretation , computerised decision support software ( CDSS ) gave a sensitivity of 87.3 % , a specificity of 99.1 % and a positive predictive value ( PPV ) of 89.5 % compared with the gold st and ard ( cardiologist reporting ) . GPs and practice nurses performed less well . The only difference in performance between intervention population s and controls was that practice nurses from the control arm performed less well than with intervention practice nurses on interpretation of limb-lead ( PPV 38.8 % versus 20.8 % ) and single-lead ( PPV 37.7 % versus 24.0 % ) ECGs . The within-trial economic evaluation results showed the lowest incremental cost to be for the opportunistic arm , with an incremental cost-effectiveness ratio of 337 pounds Sterling for each additional case detected compared to the control arm . Opportunistic screening dominated both more intensive screening strategies . Model-based analyses showed small differences in cost and quality -adjusted life-years for different methods and intensities of screening , but annual opportunistic screening result ed in the lowest number of ischaemic strokes and greatest proportion of cases of AF diagnosed . Probabilistic sensitivity results indicated that there was a probability of approximately 60 % that screening from the age of 65 years was cost-effective in both men and women . CONCLUSIONS The results of the study indicated that in terms of a screening programme for atrial fibrillation in patients 65 and over , the only strategy that improved on routine practice was opportunistic screening , model-based analyses indicated that there was a probability of approximately 60 % of annual opportunistic screening being cost effective . It is suggested that the following topics are worthy of further investigation : the effect of the implementation of a screening programme for AF on the uptake and maintenance of anticoagulation in patients aged 65 years and over ; an evaluation of the role of CDSS in the diagnosis of cardiac arrythmias ; the best method for routinely detecting paroxysmal AF ; ways of improving healthcare professionals ' performance in ECG interpretation ; development of a robust economic model to incorporate data on new therapeutic agents for use as thromboprophylactic agents for patients with AF , and an evaluation of the relative risk of stroke for patients with incident as opposed to prevalent AF", "BACKGROUND There are two approaches to the treatment of atrial fibrillation : one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm , and the other is the use of rate-controlling drugs , allowing atrial fibrillation to persist . In both approaches , the use of anticoagulant drugs is recommended . METHODS We conducted a r and omized , multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death . The primary end point was overall mortality . RESULTS A total of 4060 patients ( mean [ + /-SD ] age , 69.7+/-9.0 years ) were enrolled in the study ; 70.8 percent had a history of hypertension , and 38.2 percent had coronary artery disease . Of the 3311 patients with echocardiograms , the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent . There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy ( mortality at five years , 23.8 percent and 21.3 percent , respectively ; hazard ratio , 1.15 [ 95 percent confidence interval , 0.99 to 1.34 ] ; P=0.08 ) . More patients in the rhythm-control group than in the rate-control group were hospitalized , and there were more adverse drug effects in the rhythm-control group as well . In both groups , the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic . CONCLUSIONS Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy , and there are potential advantages , such as a lower risk of adverse drug effects , with the rate-control strategy . Anticoagulation should be continued in this group of high-risk patients", "OBJECTIVES We sought to evaluate approaches used to control rate , the effectiveness of rate control , and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . BACKGROUND The AFFIRM study showed that atrial fibrillation ( AF ) can be treated effectively with rate control and anticoagulation , but drug efficacy to control rate remains uncertain . METHODS Patients ( n = 2,027 ) r and omized to rate control in the AFFIRM study were given rate-controlling drugs by their treating physicians . St and ardized rate-control efficacy criteria developed a priori included resting heart rate and 6-min walk tests and /or ambulatory electrocardiographic results . RESULTS Average follow-up was 3.5 + /- 1.3 years . Initial treatment included a beta-adrenergic blocker ( beta-blocker ) alone in 24 % , a calcium channel blocker alone in 17 % , digoxin alone in 16 % , a beta-blocker and digoxin in 14 % , or a calcium channel blocker and digoxin in 14 % of patients . Overall rate control was achieved in 70 % of patients given beta-blockers as the first drug ( with or without digoxin ) , 54 % with calcium channel blockers ( with or without digoxin ) , and 58 % with digoxin alone . Adequate overall rate control was achieved in 58 % of patients with the first drug or combination . Multivariate analysis revealed an association between first drug class and several clinical variables . There were more changes to beta-blockers than to the other two-drug classes ( p Rate control in AF is possible in the majority of patients with AF . Beta-blockers were the most effective drugs . To achieve the goal of adequate rate control in all patients , frequent medication changes and drug combinations were needed", "BACKGROUND Atrial fibrillation is a common and treatable cause of stroke that often remains unrecognised . Screening has been suggested but there is very little evidence concerning the uptake of screening in the elderly population at risk , nor of the optimal method of screening in a general practice setting AIM To compare the uptake and effectiveness of two methods of screening for atrial fibrillation in general practice -- systematic nurse-led screening and prompted opportunistic case finding . DESIGN OF STUDY R and omised controlled trial . SETTING Patients aged 65 to 100 years ( n = 3,001 ) from four general practice s within the MRC general practice framework . METHOD Each of the four study practice s were selected from one quartile , after ranking all framework practice s according to the small area st and ardised mortality ratio of the geographical area served . Patients were r and omised either to nurse-led screening or to prompted opportunistic casefinding . The proportion of patients assessed and the proportion found to have atrial fibrillation were compared . The sensitivity and specificity of clinical assessment of pulse are also reported . RESULTS Substantially more patients had their pulse assessed through systematic screening by invitation ( 1,099/1,499 [ 73 % ] ) than through opportunistic case finding ( 439/1,502 [ 29 % ] , difference = 44 % , 95 % confidence interval [ CI ] = 41 % to 47 % ) . Atrial fibrillation was detected in 67 ( 4.5 % ) and 19 ( 1.3 % ) patients respectively ( difference = 3.2 % , 95 % CI= 2.0 to 4.4 ) . Invitation to nurse-led screening achieved significantly higher assessment rates than case finding in all practice s ; however , the proportion of patients assessed in the case-finding arm varied markedly between practice s ( range = 8 % to 52 % ) . The number needed to screen to identify one additional patient with atrial fibrillation was 31 ( 95 % CI = 23 to 50 ) . The proportion of screened patients with atrial fibrillation receiving anticoagulation treatment was 25 % , although in the majority ( 53/65 [ 82 % ] ) atrial fibrillation had been previously recorded somewhere on their medical record . If the nurse used any irregularity of the pulse as the screening criterion , the sensitivity of screening was 91 % and the specificity was 74 % ; sensitivity fell to 54 % but specificity increased to 98 % if the criterion used was continuous irregularity . CONCLUSIONS Nurse-led screening for atrial fibrillation in UK general practice is both feasible and effective and will identify a substantial number of patients who could benefit from antithrombotic therapy . Although the majority of patients detected at first screening could be identified by careful scrutiny of medical records , review of record summaries was insufficient in the practice s involved in this study and screening may be a more cost-effective option", "BACKGROUND Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke . We investigated whether anticoagulation with warfarin would reduce this risk . METHODS We conducted a r and omized , double-blind , placebo-controlled study to evaluate low-intensity anticoagulation with warfarin ( prothrombin-time ratio , 1.2 to 1.5 ) in 571 men with chronic nonrheumatic atrial fibrillation ; 525 patients had not previously had a cerebral infa rct ion , whereas 46 patients had previously had such an event . The primary end point was cerebral infa rct ion ; secondary end points were cerebral hemorrhage and death . RESULTS Among the patients with no history of stroke , cerebral infa rct ion occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years ( 4.3 percent per year ) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years ( 0.9 percent per year ) . The reduction in risk with warfarin therapy was 0.79 ( 95 percent confidence interval , 0.52 to 0.90 ; P = 0.001 ) . The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group ( risk reduction , 0.79 ; P = 0.02 ) . The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group . Other major hemorrhages , all gastrointestinal , occurred in 10 patients : 4 in the placebo group , for a rate of 0.9 percent per year , and 6 in the warfarin group , for a rate of 1.3 percent per year . There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group ( risk reduction , 0.31 ; P = 0.19 ) . Cerebral infa rct ion was more common among patients with a history of cerebral infa rct ion ( 9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group ) than among those without such a history . CONCLUSIONS Low-intensity anticoagulation with warfarin prevented cerebral infa rct ion in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage . This benefit extended to patients over 70 years of age", "OBJECTIVE Atrial fibrillation is often asymptomatic , but outcomes require further characterization . The study objective was to investigate the clinical presentation , management , and outcomes in asymptomatic and symptomatic patients with atrial fibrillation who were prospect ively enrolled in the EurObservational Research Programme - Atrial Fibrillation ( EORP-AF ) Pilot General Registry . METHODS A total of 3119 patients were enrolled , and 1237 ( 39.7 % ) were asymptomatic ( European Heart Rhythm Association [ EHRA ] score I ) . Among symptomatic patients , 963 ( 51.2 % ) had mild symptoms ( EHRA score II ) and 919 ( 48.8 % ) had severe or disabling symptoms ( EHRA III-IV ) . Permanent atrial fibrillation was 3-fold more common in asymptomatic patients than in symptomatic patients . RESULTS On multivariate analysis , male gender ( odds ratio [ OR ] , 1.630 ; 95 % confidence interval [ CI ] , 1.384 - 1.921 ) , older age ( OR , 1.019 ; 95 % CI , 1.012 - 1.026 ) , previous myocardial infa rct ion ( OR , 1.681 ; 95 % CI , 1.350 - 2.093 ) , and limited physical activity ( OR , 1.757 ; 95 % CI , 1.495 - 2.064 ) were associated significantly with asymptomatic ( EHRA I ) atrial fibrillation . Fully asymptomatic atrial fibrillation ( absence of current and previous symptoms ) was present in 520 patients ( 16.7 % ) and was associated independently with male gender , age , and previous myocardial infa rct ion . Appropriate guideline -based prescription of oral anticoagulants was lower in these patients , and aspirin was prescribed more frequently . Mortality at 1 year was more than 2-fold higher in asymptomatic patients compared with symptomatic patients ( 9.4 % vs 4.2 % , P 1-year mortality was found in asymptomatic patients compared with symptomatic patients" ]

[ "Objective To evaluate the effects of water versus beverages sweetened with non‐nutritive sweeteners ( NNS ) on body weight in subjects enrolled in a year‐long behavioral weight loss treatment program . Methods The study used a r and omized equivalence design with NNS or water beverages as the main factor in a trial among 303 weight‐stable people with overweight and obesity . All participants participated in a weight loss program plus assignment to consume 24 ounces ( 710 ml ) of water or NNS beverages daily for 1 year . Results NNS and water treatments were non‐equivalent , with NNS treatment showing greater weight loss at the end of 1 year . At 1 year subjects receiving water had maintained a 2.45 ± 5.59 kg weight loss while those receiving NNS beverages maintained a loss of 6.21 ± 7.65 kg ( P Conclusions Water and NNS beverages were not equivalent for weight loss and maintenance during a 1‐year behavioral treatment program . NNS beverages were superior for weight loss and weight maintenance in a population consisting of regular users of NNS beverages who either maintained or discontinued consumption of these beverages and consumed water during a structured weight loss program . These results suggest that NNS beverages can be an effective tool for weight loss and maintenance within the context of a weight management program", "To investigate whether obese women can compensate for sucrose added to the diet when it is given blind , rather than gaining weight or exhibiting dysfunctional regulation of intake , in the present study , forty-one healthy obese ( BMI 30–35 kg/m2 ) women ( age 20–50 years ) , not currently dieting , were r and omly assigned to consume sucrose ( n 20 ) or aspartame ( n 21 ) drinks over 4 weeks in a parallel single-blind design . Over the 4 weeks , one group consumed 4 × 250 ml sucrose drinks ( total 1800 kJ/d ) and the other group consumed 4 × 250 ml aspartame drinks . During the baseline week and experimental weeks , body weight and other biometric data were measured and steps per day , food intake using 7 d unweighed food diaries , and mood using ten- or seven-point Likert scales four times a day were recorded . At the end of the experiment , the participants weighed 1·72 ( se 0·47 ) kg less than the value predicted by the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) model ; the predicted body weight accounted for 94·3 % of the variance in the observed body weight and experimental group accounted for a further 1·1 % of the variance in the observed body weight , showing that women consuming sucrose drinks gained significantly less weight than predicted . The reported daily energy intake did not increase significantly , and sucrose supplements significantly reduced the reported voluntary sugar , starch and fat intake compared with aspartame . There were no effects on appetite or mood . Over 4 weeks , as part of everyday eating , sucrose given blind in soft drinks was partially compensated for by obese women , as in previous experiments with healthy and overweight participants", "The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P fat ( F(2,250 ) = 33.33 ; P protein intake ( F(2,250 ) = 28.04 ; P sweetener supplements . Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects", "BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . )", "This study investigated whether the addition of the high-intensity sweetener aspartame to a multidisciplinary weight-control program would improve weight loss and long-term control of body weight . One hundred sixty-three obese women were r and omly assigned to consume or to abstain from aspartame-sweetened foods and beverages during 16 wk of a 19-wk weight-reduction program ( active weight loss ) , a 1-y maintenance program , and a 2-y follow-up period . Women in both treatment groups lost approximately 10 % of initial body weight ( 10 kg ) during active weight loss . Among women assigned to the aspartame-treatment group , aspartame intake was positively correlated with percentage weight loss during active weight loss ( r = 0.32 , P regain of initial body weight after 71 and 175 wk , respectively , whereas those in the no-aspartame group gained an average of 5.4 % ( 5.4 kg ) and 9.4 % ( 9.4 kg ) , respectively . The aspartame group lost significantly more weight overall ( P = 0.028 ) and regained significantly less weight during maintenance and follow-up ( P = 0.046 ) than did the no-aspartame group . Percentage weight losses at 71 and 175 wk were also positively correlated with exercise ( r = 0.32 , P eating control ( r = 0.37 , P aspartame may facilitate the long-term maintenance of reduced body weight", "Background : Beneficial effects of replacing diet beverages ( DBs ) with water on weight loss , during a 24-week hypoenergetic diet were previously observed . However , it is not known whether this difference is sustained during a subsequent 12-month weight maintenance period . Objective : To evaluate effects of replacing DBs with water on body weight maintenance over a 12-month period in participants who undertook a 6-month weight loss plan . Design : Seventy-one obese and overweight adult women ( body mass index ( BMI ): 27–40 kg m–2 ; age : 18–50 years ) who usually consumed DBs in their diet were r and omly assigned to either substitute water for DBs ( water group : 35 ) or continue drinking DBs five times per week ( DBs group : 36 ) after their lunch for the 6-month weight loss intervention and subsequent 12-month weight maintenance program . Results : A total of 71 participants who were r and omly assigned were included in the study by using an intention-to-treat analysis . Greater additional weight loss ( mean±s.d . ) in the water group was observed compared with the DBs group after the 12-month follow-up period ( −1.7±2.8 vs −0.1±2.7 kg , P=0.001 ) . BMI decreased more in the water group than in the DBs group ( −0.7±1 vs −0.05±1.1 kg m–2 , P=0.003 ) . There was also a greater reduction in fasting insulin levels ( −0.5±1.4 vs −0.02±1.5 mmol l–1 , P=0.023 ) , better improvement in homeostasis model assessment of insulin resistance ( −0.2±0.4 vs −0.1±0.3 , P=0.013 ) and a greater decrease in 2-h postpr and ial plasma glucose ( −0.2±0.3 vs −0.1±0.3 mmol l–1 , P Replacement of DBs with water after the main meal in women who were regular users of DBs may cause further weight reduction during a 12-month weight maintenance program . It may also offer benefits in carbohydrate metabolism including improvement of insulin resistance over the long-term weight maintenance period", "Background Low-calorie sweeteners are often used to moderate energy intake and postpr and ial glycemia , but some evidence indicates that they may exacerbate these aims . Objective The trial 's primary aim was to assess the effect of daily aspartame ingestion for 12 wk on glycemia . Effects on appetite and body weight were secondary aims . Methods One hundred lean [ body mass index ( kg/m2 ) : 18 - 25 ] adults aged 18 - 60 y were r and omly assigned to consume 0 , 350 , or 1050 mg aspartame/d ( ASP groups ) in a beverage for 12 wk in a parallel-arm design . At baseline , body weight and composition were determined , a 240-min oral-glucose-tolerance test ( OGTT ) was administered , and measurements were made of appetite and selected hormones . Participants also collected a 24-h urine sample . During the intervention , the 0-mg/d ASP group consumed capsules containing 680 mg dextrose and 80 mg para-amino benzoic acid . For the 350-mg/d ASP group , the beverage contained 350 mg aspartame and the 1050-mg/d ASP group consumed the same beverage plus capsules containing 680 mg dextrose and 700 mg aspartame . Body weight , blood pressure , heart rate , and waist circumference were measured weekly . At weeks 4 , 8 , and 12 , participants collected 24-h urine sample s and kept appetite logs . Baseline measurements were repeated at week 12 . Results With the exception of the baseline OGTT glucose concentration at 60 min ( and result ing area under the curve value ) , there were no group differences for glucose , insulin , resting leptin , glucagon-like peptide 1 , or gastric inhibitory peptide at baseline or week 12 . There also were no effects of aspartame ingestion on appetite , body weight , or body composition . Compliance with the beverage intervention was ∼95 % . Conclusions Aspartame ingested at 2 doses for 12 wk had no effect on glycemia , appetite , or body weight among healthy , lean adults . These data do not support the view that aspartame is problematic for the management of glycemia , appetite , or body weight . This trial was registered at www . clinical trials.gov as NCT02999321", "BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P skeletal muscle fat ( 117 - 221 % ; P visceral fat ( 24 - 31 % ; P blood triglycerides ( 32 % ; P total cholesterol ( 11 % ; P Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647", "OBJECTIVE To test the hypothesis that substituting artificially sweetened beverages ( ASB ) for sugar-sweetened beverages ( SSB ) decreases intrahepatocellular lipid concentrations ( IHCL ) in overweight subjects with high SSB consumption . METHODS About 31 healthy subjects with BMI greater than 25 kg/m(2 ) and a daily consumption of at least 660 ml SSB were r and omized to a 12-week intervention in which they replaced SSBs with ASBs . Their IHCL ( magnetic resonance spectroscopy ) , visceral adipose tissue volume ( VAT ; magnetic resonance imaging ) , food intake ( 2-day food records ) , and fasting blood concentrations of metabolic markers were measured after a 4-week run-in period and after a 12-week period with ASB or control ( CTRL ) . RESULTS About 27 subjects completed the study . IHCL was reduced to 74 % of the initial values with ASB ( N = 14 ; P IHCL attained with ASB was more important in subjects with IHCL greater than 60 mmol/l than in subjects with low IHCL . ALT decreased significantly with SSB only in subjects with IHCL greater than 60 mmol/l . There was otherwise no significant effect of ASB on body weight , VAT , or metabolic markers . CONCLUSIONS In subjects with overweight or obesity and a high SSB intake , replacing SSB with ASB decreased intrahepatic fat over a 12-week period", "BACKGROUND Consumption of sugar-sweetened beverages may cause excessive weight gain . We aim ed to assess the effect on weight gain of an intervention that included the provision of noncaloric beverages at home for overweight and obese adolescents . METHODS We r and omly assigned 224 overweight and obese adolescents who regularly consumed sugar-sweetened beverages to experimental and control groups . The experimental group received a 1-year intervention design ed to decrease consumption of sugar-sweetened beverages , with follow-up for an additional year without intervention . We hypothesized that the experimental group would gain weight at a slower rate than the control group . RESULTS Retention rates were 97 % at 1 year and 93 % at 2 years . Reported consumption of sugar-sweetened beverages was similar at baseline in the experimental and control groups ( 1.7 servings per day ) , declined to nearly 0 in the experimental group at 1 year , and remained lower in the experimental group than in the control group at 2 years . The primary outcome , the change in mean body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) at 2 years , did not differ significantly between the two groups ( change in experimental group minus change in control group , -0.3 ; P=0.46 ) . At 1 year , however , there were significant between-group differences for changes in BMI ( -0.57 , P=0.045 ) and weight ( -1.9 kg , P=0.04 ) . We found evidence of effect modification according to ethnic group at 1 year ( P=0.04 ) and 2 years ( P=0.01 ) . In a prespecified analysis according to ethnic group , among Hispanic participants ( 27 in the experimental group and 19 in the control group ) , there was a significant between-group difference in the change in BMI at 1 year ( -1.79 , P=0.007 ) and 2 years ( -2.35 , P=0.01 ) , but not among non-Hispanic participants ( P>0.35 at years 1 and 2 ) . The change in body fat as a percentage of total weight did not differ significantly between groups at 2 years ( -0.5 % , P=0.40 ) . There were no adverse events related to study participation . CONCLUSIONS Among overweight and obese adolescents , the increase in BMI was smaller in the experimental group than in the control group after a 1-year intervention design ed to reduce consumption of sugar-sweetened beverages , but not at the 2-year follow-up ( the prespecified primary outcome ) . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00381160 . )", "OBJECTIVE . The role of sugar-sweetened beverages ( SSBs ) in promoting obesity is controversial . Observational data link SSB consumption with excessive weight gain ; however , r and omized , controlled trials are lacking and necessary to resolve the debate . We conducted a pilot study to examine the effect of decreasing SSB consumption on body weight . METHODS . We r and omly assigned 103 adolescents aged 13 to 18 years who regularly consumed SSBs to intervention and control groups . The intervention , 25 weeks in duration , relied largely on home deliveries of noncaloric beverages to displace SSBs and thereby decrease consumption . Change in SSB consumption was the main process measure , and change in body mass index ( BMI ) was the primary end point . RESULTS . All of the r and omly assigned subjects completed the study . Consumption of SSBs decreased by 82 % in the intervention group and did not change in the control group . Change in BMI , adjusted for gender and age , was 0.07 ± 0.14 kg/m2 ( mean ± SE ) for the intervention group and 0.21 ± 0.15 kg/m2 for the control group . The net difference , −0.14 ± 0.21 kg/m2 , was not significant overall . However , baseline BMI was a significant effect modifier . Among the subjects in the upper baseline- BMI tertile , BMI change differed significantly between the intervention ( −0.63 ± 0.23 kg/m2 ) and control ( + 0.12 ± 0.26 kg/m2 ) groups , a net effect of −0.75 ± 0.34 kg/m2 . The interaction between weight change and baseline BMI was not attributable to baseline consumption of SSBs . CONCLUSIONS . A simple environmental intervention almost completely eliminated SSB consumption in a diverse group of adolescents . The beneficial effect on body weight of reducing SSB consumption increased with increasing baseline body weight , offering additional support for American Academy of Pediatrics guidelines to limit SSB consumption", "This study was conducted to determine the effects and the differences , if any , result ing from the ingestion of aspartame ( sweetener ) versus sucrose . A 13-wk , double-blind study was conducted using 126 apparently healthy children and adolescents as panelists . Individuals were r and omly assigned in a double-blind design to aspartame or sucrose in each of five age groups ; dosage levels were assigned according to age and weight groups . Physical examinations and special eye examinations were performed at the beginning and end of the study . Other parameters determined including laboratory tests of liver and renal function , hematologic status , and plasma levels of phenylalanine and tyrosine . Clinical ly significant differences in laboratory parameters measured could not be demonstrated ; all mean values were within normal limits . No unusual findings were observed in phenylalanine or tyrosine levels . All phenylpyruvic acid and methanol determinations were negative . No important physical changes occurred , and no product-related side effects were reported", "Background The rules for reporting the results of r and omized controlled trials ( RCTs ) in published manuscripts have been elusive , and many nurse scientists have learned to write research reports by trial and error . ApproachNew comprehensive guidelines for reporting RCTs are now available to authors , editors , and readers , a development that is likely to improve the quality of published reports . The Consoli date d St and ards of Reporting Trials ( CONSORT ) guidelines consist of two parts , a 22-item checklist and a flowchart template , that track the flow of all participants through the RCT . Currently , some journals , including Nursing Research , have adopted CONSORT and suggest or require its use in su bmi tted manuscripts , but other journals do not . Results The CONSORT has potential to be useful beyond writing manuscripts . Because CONSORT is a comprehensive guide to essential elements of an RCT report , it also provides a useful guide for design ing RCTs and writing funding proposals that include all the essential elements of a trial . It also could be a useful synopsis of important concepts when teaching research design to doctoral students . Discussion Reports of RCTs that use CONSORT are easier to read , interpret , and evaluate for relevancy to clinical practice . In addition , excellent reports of research increase the visibility of nursing research beyond our discipline . The CONSORT adds value to nursing research because research ers and readers alike will benefit if it is used more often", "Rebaudioside A and stevioside are steviol glycosides extracted from the plant Stevia rebaudiana Bertoni and are used in several countries as food and beverage sweeteners . This r and omized , double-blind trial evaluated the hemodynamic effects of 4weeks consumption of 1000mg/day rebaudioside A vs. placebo in 100 individuals with normal and low-normal systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) . Subjects were predominantly female ( 76 % , rebaudioside A and 82 % , placebo ) with a mean age of approximately 41 ( range 18 - 73 ) years . At baseline , mean resting , seated SBP/DBP was 110.0/70.3mmHg and 110.7/71.2mmHg for the rebaudioside A and placebo groups , respectively . Compared with placebo , rebaudioside A did not significantly alter resting , seated SBP , DBP , mean arterial pressure ( MAP ) , heart rate ( HR ) or 24-h ambulatory blood pressures responses . These results indicate that consumption of as much as 1000mg/day of rebaudioside A produced no clinical ly important changes in blood pressure in healthy adults with normal and low-normal blood pressure", "Given the potential use of a low-calorie sweetener during weight reduction , a toxicity study of chronic aspartame ingestion was conducted . Particular attention was given to possible long-term effects of aspartame on the fuel hormonal alterations characteristically caused by weight reduction . As a group mean age was 19.3 yr , body weight was 164.6 lb , and mean height was 65.4 in . Subjects were an average of 33 % in excess of ideal body weight . The aspartame dose was 2.7 g/day and was compared on a double-blind r and omized basis with a lactose placebo . Both material s were given in gelatin capsules . An average of 6.9 + /- 1.5 lb was lost by the aspartame group during the 13-wk study on a calculated 1,000-calorie diet . The placebo group lost 4.5 + /- 1.2 lb ( no significant difference between the two groups ) . After an overnight fast , reductions in glucose and immunoreactive insulin were seen in both groups , while rising trends in immunoreactive glucagon were observed . These changes are all characteristic of calorie restriction . In no instance was there a detectable effect of the ingested aspartame . No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol , nor on any other parameter of hematologic , hepatic , or renal function that was measured . Similarly , side effects were equally distributed between asparatame and placebo", "This study explores whether the addition of aspartame-sweetened foods and beverages to a low fat , hypocaloric diet enhances compliance and result ing weight loss . Fifty-nine obese ( 130 - 225 % of ideal body weight ) , free living men and women were r and omly assigned to either a Balanced Deficit Diet ( BDD ) or a BDD supplemented with aspartame . Over a 12-week weight loss period , volunteers attended weekly support group meetings including behavior modification training and exercise instruction . Males achieved a clinical ly significant weight loss ( greater than 23 lb ) in both study groups , while females lost an average of 12.8 lb in the control group vs. 16.5 lb in the experimental group . In both treatment groups , sleep , general energy level , level of physical activity , and feeling of well-being showed clinical ly meaningful improvement . This study suggests possible advantages to supplementing a BDD with aspartame-sweetened foods as part of a multidisciplinary weight loss program . The small sample size prohibits definitive conclusions but does provide the protocol for a larger , outpatient clinical trial", "BACKGROUND Low-calorie sweeteners ( LCSs ) provide sweetness with little or no energy . However , each LCS 's unique chemical structure has potential to elicit different sensory , physiological , and behavioral responses that affect body weight . OBJECTIVE The purpose of this trial was to compare the effects of consumption of 4 LCSs and sucrose on body weight , ingestive behaviors , and glucose tolerance over a 12-wk intervention in adults ( 18 - 60 y old ) with overweight or obesity ( body mass index 25 - 40 kg/m2 ) . METHODS In a parallel-arm design , 154 participants were r and omly assigned to consume 1.25 - 1.75 L of beverage sweetened with sucrose ( n = 39 ) , aspartame ( n = 30 ) , saccharin ( n = 29 ) , sucralose ( n = 28 ) , or rebaudioside A ( rebA ) ( n = 28 ) daily for 12 wk . The beverages contained 400 - 560 kcal/d ( sucrose treatments ) or ( LCS treatments ) . Anthropometric indexes , energy intake , energy expenditure , appetite , and glucose tolerance were measured at baseline . Body weight was measured every 2 wk with energy intake , expenditure , and appetite assessed every 4 wk . Twenty-four-hour urine collection s were completed every 4 wk to determine study compliance via para-aminobenzoic acid excretion . RESULTS Of the participants enrolled in the trial , 123 completed the 12-wk intervention . Sucrose and saccharin consumption led to increased body weight across the 12-wk intervention ( Δweight = + 1.85 ± 0.36 kg and + 1.18 ± 0.36 kg , respectively ; P ≤ 0.02 ) and did not differ from each other . There was no significant change in body weight with consumption of the other LCS treatments compared with baseline , but change in body weight for sucralose was negative and significantly lower compared with all other LCSs at week 12 ( weight difference ≥ 1.37 ± 0.52 kg , P ≤ 0.008 ) . Energy intake decreased with sucralose consumption ( P = 0.02 ) and ingestive frequency was lower for sucralose than for saccharin ( P = 0.045 ) . Glucose tolerance was not significantly affected by any of the sweetener treatments . CONCLUSIONS Sucrose and saccharin consumption significantly increase body weight compared with aspartame , rebA , and sucralose , whereas weight change was directionally negative and lower for sucralose compared with saccharin , aspartame , and rebA consumption . LCSs should be categorized as distinct entities because of their differing effects on body weight . This trial was registered at clinical trials.gov as NCT02928653", "The long-term effects of sucrose on appetite and mood remain unclear . Normal weight subjects compensate for sucrose added blind to the diet ( Reid et al. , 2007 ) . Overweight subjects , however , may differ . In a single-blind , between-subjects design , soft drinks ( 4x25cl per day ; 1800kJ sucrose sweetened versus 67kJ aspartame sweetened ) were added to the diet of overweight women ( n=53 , BMI 25 - 30 , age 20 - 55 ) for 4 weeks . A 7-day food diary gave measures of total energy , carbohydrate , protein , fat , and micronutrients . Mood and hunger were measured by ten single Likert scales rated daily at 11.00 , 14.00 , 16.00 , and 20.00 . Activity levels were measured by diary and pedometer . Baseline energy intake did not differ between groups . During the first week of the intervention energy intake increased slightly in the sucrose group , but not in the aspartame group , then decreased again , so by the final week intake again did not differ from the aspartame group . Compensation was not large enough to produce significant changes in the composition of the voluntary diet . There were no effects on hunger or mood . It is concluded that overweight women do not respond adversely to sucrose added blind to the diet , but compensate for it by reducing voluntary energy intake . Alternative explanations for the correlation between sugary soft drink intake and weight gain are discussed" ]

[ "Overweight and obesity affects more than 66 % of the adult population and is associated with a variety of chronic diseases . Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies . Guidelines of the National Heart , Lung , and Blood Institute ( NHLBI ) encourage a 10 % reduction in weight , although considerable literature indicates reduction in health risk with 3 % to 5 % reduction in weight . Physical activity ( PA ) is recommended as a component of weight management for prevention of weight gain , for weight loss , and for prevention of weight regain after weight loss . In 2001 , the American College of Sports Medicine ( ACSM ) published a Position St and that recommended a minimum of 150 min wk(-1 ) of moderate-intensity PA for overweight and obese adults to improve health ; however , 200 - 300 min wk(-1 ) was recommended for long-term weight loss . More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss . To this end , we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain , for weight loss , and prevention of weight regain . Evidence supports moderate-intensity PA between 150 and 250 min wk(-1 ) to be effective to prevent weight gain . Moderate-intensity PA between 150 and 250 min wk(-1 ) will provide only modest weight loss . Greater amounts of PA ( > 250 min wk(-1 ) ) have been associated with clinical ly significant weight loss . Moderate-intensity PA between 150 and 250 min wk(-1 ) will improve weight loss in studies that use moderate diet restriction but not severe diet restriction . Cross-sectional and prospect i ve studies indicate that after weight loss , weight maintenance is improved with PA > 250 min wk(-1 ) . However , no evidence from well- design ed r and omized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss . Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk . Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk . There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain", "INTRODUCTION The aims of this prospect i ve cohort study were to examine 16-year trajectories of weight and BMI in young adult women who had a healthy BMI in 1996 and determinants of remaining in the healthy BMI category . METHODS A total of 4,881 women with healthy BMI at baseline and either healthy , overweight , or obese BMI at 16-year follow-up reported their weight , height , health , and health behaviors in six surveys of the Australian Longitudinal Study on Women 's Health between 1996 ( aged 18 - 23 years ) and 2012 ( aged 34 - 39 years ) . Determinants of BMI maintenance were estimated using binary logistic regression and generalized estimating equations in 2015 . RESULTS Almost 60 % remained in the healthy BMI category from 1996 to 2012 , ( mean weight gain , 0.19 kg/year ) , 29 % transitioned to overweight BMI ( 0.83 kg/year ) , and 11.6 % transitioned to obese ( 1.73 kg/year ) . The mean rates of annual weight gain in each group were consistent over time . Only three factors ( low alcohol , moderate/high physical activity , having a university degree ) were positively associated with maintaining a healthy BMI . Additional behavioral factors ( smoking , high sitting time , energy intake , dieting , takeaway food , and use of oral contraceptives ) , as well as blue collar occupation , separation/divorce/widowhood , and major illness were negatively associated with BMI maintenance . CONCLUSIONS To prevent the transition from healthy to overweight/obese BMI , weight gain must be limited to weight gain in their early 20s , could be identified by health professionals for assistance with prevention of becoming overweight/obese", "Background / Objectives : Despite considerable research on the association between physical activity ( PA ) and body composition , there remains limited information on the directionality of the relationship . The present study examined the prospect i ve associations among objective ly measured PA , energy intake ( EI ) and body composition . Subjects/ Methods : A convenience sample of 430 adults ( 49 % male ) between 21 and 35 years of age was followed over 1 year with repeated measurements taken every 3 months . BMI ( kg/m2 ) and percent body fat ( % BF ) were calculated based on anthropometric measurements and dual energy X-ray absorptiometry . A multi-sensor device was worn over a period of 10 days to estimate total daily energy expenditure and time spent in different intensities . EI was calculated based on change in body composition and total daily energy expenditure . Results : A total of 379 participants provided valid data . On average , participants experienced a significant weight gain of 1.2±4.3 kg during the 12-month observation period , which was associated with an increase in % BF ( 0.8±3.2 % ) . Average time spent in moderate-to-vigorous PA ( MVPA ) decreased significantly , whereas EI remained constant . Optimal linear mixed models , adjusting for age and sex , showed an inverse effect of MVPA on BMI and % BF , whereas EI only directly affected BMI ( P of BMI and % BF on MVPA ( P and low PA", "BACKGROUND Sedentary behavior is a risk factor for cardiometabolic disease . Regularly interrupting sedentary behavior with activity breaks may lower this risk . OBJECTIVE We compared the effects of prolonged sitting , continuous physical activity combined with prolonged sitting , and regular activity breaks on postpr and ial metabolism . DESIGN Seventy adults participated in a r and omized crossover study . The prolonged sitting intervention involved sitting for 9 h , the physical activity intervention involved walking for 30 min and then sitting , and the regular-activity-break intervention involved walking for 1 min 40 s every 30 min . Participants consumed a meal-replacement beverage at 60 , 240 , and 420 min . RESULTS The plasma incremental area under the curve ( iAUC ) for insulin differed between interventions ( overall P Regular activity breaks lowered values by 866.7 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 506.0 , 1227.5 IU · L(-1 ) · 9 h(-1 ) ; P with prolonged sitting and by 542.0 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 179.9 , 904.2 IU · L(-1 ) · 9 h(-1 ) ; P = 0.003 ) when compared with physical activity . Plasma glucose iAUC also differed between interventions ( overall P . Regular activity breaks lowered values by 18.9 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 10.0 , 28.0 mmol · L(-1 ) · 9 h(-1 ) ; P with prolonged sitting and by 17.4 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 8.4 , 26.3 mmol · L(-1 ) · 9 h(-1 ) ; P compared with physical activity . Plasma triglyceride iAUC differed between interventions ( overall P = 0.023 ) . Physical activity lowered values by 6.3 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 1.8 , 10.7 mmol · L(-1 ) · 9 h(-1 ) ; P = 0.006 ) when compared with regular activity breaks . CONCLUSION Regular activity breaks were more effective than continuous physical activity at decreasing postpr and ial glycemia and insulinemia in healthy , normal-weight adults . This trial was registered with the Australian New Zeal and Clinical Trials registry as ACTRN12610000953033", "Aims Type 2 diabetes mellitus ( T2DM ) , a serious and prevalent chronic disease , is traditionally associated with older age . However , due to the rising rates of obesity and sedentary lifestyles , it is increasingly being diagnosed in the younger population . Sedentary ( sitting ) behaviour has been shown to be associated with greater risk of cardio-metabolic health outcomes , including T2DM . Little is known about effective interventions to reduce sedentary behaviour in younger adults at risk of T2DM . We aim ed to investigate , through a r and omised controlled trial ( RCT ) design , whether a group-based structured education workshop focused on sitting reduction , with self-monitoring , reduced sitting time . Methods Adults aged 18–40 years who were either overweight ( with an additional risk factor for T2DM ) or obese were recruited for the Sedentary Time ANd Diabetes ( ST AND ) RCT . The intervention programme comprised of a 3-hour group-based structured education workshop , use of a self-monitoring tool , and follow-up motivational phone call . Data were collected at three time points : baseline , 3 and 12 months after baseline . The primary outcome measure was accelerometer-assessed sedentary behaviour after 12 months . Secondary outcomes included other objective ( activPAL ) and self-reported measures of sedentary behaviour and physical activity , and biochemical , anthropometric , and psycho-social variables . Results 187 individuals ( 69 % female ; mean age 33 years ; mean BMI 35 kg/m2 ) were r and omised to intervention and control groups . 12 month data , when analysed using intention-to-treat analysis ( ITT ) and per- protocol analyses , showed no significant difference in the primary outcome variable , nor in the majority of the secondary outcome measures . Conclusions A structured education intervention design ed to reduce sitting in young adults at risk of T2DM was not successful in changing behaviour at 12 months . Lack of change may be due to the brief nature of such an intervention and lack of focus on environmental change . Moreover , some participants reported a focus on physical activity rather than reductions in sitting per se . The habitual nature of sedentary behaviour means that behaviour change is challenging . Trial Registration Controlled-Trials.com IS RCT", "Objective Evidence on the direction of the association between sitting time and obesity is limited . The prospect i ve associations between baseline total sitting time and subsequent changes in body mass index ( BMI ) , and baseline BMI and subsequent changes in sitting time were examined . Methods BMI , from self-reported height and weight , and a single-item measure of sitting time were ascertained at two time points ( 3.4 ± 0.96 years apart ) in a prospect i ve question naire-based cohort of 31,787 Australians aged 45–65 years without severe physical limitations . Results In a fully adjusted model , baseline obesity was associated with increased sitting time among all participants ( adjusted odds ratio [ aOR ] = 1.20 [ 95 % CI , 1.11 - 1.30 ] ; P were sitting association between baseline sitting time and subsequent change in BMI . Conclusions Our findings support the hypothesis that obesity may lead to a subsequent increase in total sitting time , but the association in the other direction is unclear", "BACKGROUND Although it is known that abdominal obesity increases the risk of chronic diseases , prospect i ve data examining the relation between lifestyle factors and the accumulation of abdominal adipose tissue are sparse . OBJECTIVE The objective of the study was to determine the associations of changes in diet , physical activity , alcohol consumption , and smoking with 9-y waist gain among US men . DESIGN A prospect i ve cohort comprised 16 587 US men aged 40 - 75 y at baseline in 1986 . Data on lifestyle factors were provided periodically with the use of self-reported question naires , and participants measured and reported their waist circumference in 1987 and 1996 . RESULTS In multivariate analyses , a 2 % increment in energy intake from trans fats that were isocalorically substituted for either polyunsaturated fats or carbohydrates was significantly associated with a 0.77-cm waist gain over 9 y ( P total fiber/d was associated with a 0.63-cm decrease in waist circumference ( P television watching were associated with a 1.98-cm and 0.59-cm waist gain , respectively ( P physical activity and of > /= 0.5 h/wk in weight training were associated with 0.38-cm and 0.91-cm decreases in waist circumference , respectively ( P in total fat and alcohol consumption and in walking volume were not significantly related to waist gain . CONCLUSIONS Waist gain may be modulated by changes in trans fat and fiber consumption , smoking cessation , and physical activity ", "OBJECTIVE Observational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers , but intervention studies are required to investigate causality . We examined the acute effects on postpr and ial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking . RESEARCH DESIGN AND METHODS Overweight/obese adults ( n = 19 ) , aged 45–65 years , were recruited for a r and omized three-period , three-treatment acute crossover trial : 1 ) uninterrupted sitting ; 2 ) seated with 2-min bouts of light-intensity walking every 20 min ; and 3 ) seated with 2-min bouts of moderate-intensity walking every 20 min . A st and ardized test drink was provided after an initial 2-h period of uninterrupted sitting . The positive incremental area under curves ( iAUC ) for glucose and insulin ( mean [ 95 % CI ] ) for the 5 h after the test drink ( 75 g glucose , 50 g fat ) were calculated for the respective treatments . RESULTS The glucose iAUC ( mmol/L ) ⋅ h after both activity-break conditions was reduced ( light : 5.2 [ 4.1–6.6 ] ; moderate : 4.9 [ 3.8–6.1 ] ; both P compared with uninterrupted sitting ( 6.9 [ 5.5–8.7 ] ) . Insulin iAUC ( pmol/L ) ⋅ h was also reduced with both activity-break conditions ( light : 633.6 [ 552.4–727.1 ] ; moderate : 637.6 [ 555.5–731.9 ] , P compared with uninterrupted sitting ( 828.6 [ 722.0–950.9 ] ) . CONCLUSIONS Interrupting sitting time with short bouts of light- or moderate-intensity walking lowers postpr and ial glucose and insulin levels in overweight/obese adults . This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk ", "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 Prospect i ve studies report associations between indicators of time spent sitting and obesity risk . Most studies use a single indicator of sedentary behavior and are unable to clearly identify whether sedentary behavior is a cause or a consequence of obesity . Purpose To investigate cross-sectional and prospect i ve associations between multiple sitting time indicators and obesity and examine the possibility of reverse causality . Methods Using data from the Whitehall II cohort , multiple logistic models were fitted to examine associations between prevalent obesity ( BMI ≥30 ) at Phase 5 ( 1997–1999 ) , and incident obesity between Phases 5 and 7 ( 2003–2004 ) across four levels of five sitting exposures ( work sitting , TV viewing , non-TV leisure-time sitting , leisure-time sitting , and total sitting ) . Using obesity data from three prior phases ( 1985–1988 , 1991–1993 ; and recalled weight at age 25 years ) , linear regression models were fitted to examine the association between prior obesity and sitting time at Phase 5 . Analyses were conducted in 2012 . Results None of the sitting exposures were associated with obesity either cross-sectionally or prospect ively . Obesity at one previous measurement phase was associated with a 2.43-hour/week ( 95 % CI=0.07 , 4.78 ) increase in TV viewing ; obesity at three previous phases was associated with a 7.42-hour/week ( 95 % CI=2.7 , 12.46 ) increase in TV-viewing hours/week at Phase 5 . Conclusions Sitting time was not associated with obesity cross-sectionally or prospect ively . Prior obesity was prospect ively associated with time spent watching TV per week but not other types of sitting", "Objectives It is unclear whether sedentary behaviour , and the domain in which it occurs , is related to body mass index ( BMI ) change . We aim to eluci date whether sedentary behaviour is prospect ively related to BMI change using markers from three domains ( leisure , work and commuting ) . Methods Among employed 1958 British birth cohort members ( n = 6,562 ) , we analysed whether TV-viewing , work sitting ( six categories : 0 h/d to > 4 h/d ) and motorised commuting ( at 45 y ) were related to BMI ( at 45 y and 50 y ) and BMI change 45–50 y , after adjusting for lifestyle and socioeconomic factors . Results Per category higher TV-viewing , 45 y and 50 y BMI were higher by 0.69 kg/m2 ( 95 % CI : 0.59,0.80 ) and 0.75 kg/m2 ( 0.64,0.86 ) respectively . A category higher TV-viewing was associated with 0.11 kg/m2 ( 0.06,0.17 ) increased BMI 45–50 y , attenuating to 0.06 kg/m2 ( 0.01,0.12 ) after adjustment . There was no trend for work sitting with 45 y or 50 y BMI , nor , after adjustment , for BMI change . However , those sitting 2–3 h/d had greater BMI gain by 0.33 kg/m2 ( 0.10,0.56 ) compared to those sitting 0–1 h/d . Associations between TV-viewing and BMI change were independent of work sitting . Motorised commuting was associated with 45 y , but not 50 y BMI or change . Conclusions TV-viewing is associated with BMI gain in mid-adulthood ; evidence is weaker for other sedentary behaviours", "ABSTRACT Purpose Both moderate-to-vigorous physical activity ( MVPA ) and sedentary behavior can be associated with adult adiposity . Much of the relevant evidence is from cross-sectional studies or from prospect i ve studies with relevant exposure measures at a single time point before weight gain or incident obesity . This study examined whether changes in MVPA and television ( TV ) viewing time are associated with subsequent changes in waist circumference , using data from three separate observation points in a large population -based prospect i ve study of Australian adults . Methods Data were obtained from the Australian Diabetes , Obesity , and Lifestyle study collected in 1999–2000 ( baseline ) , 2004–2005 ( wave 2 ) , and 2011–2012 ( wave 3 ) . The study sample consisted of adults age 25 to 74 yr at baseline who also attended site measurement at three time points ( n = 3261 ) . Multilevel linear regression analysis examined associations of initial 5-yr changes in MVPA and TV viewing time ( from baseline to wave 2 ) with 12-yr change in waist circumference ( from baseline to wave 3 ) , adjusting for well-known confounders . Results As categorical predictors , increases in MVPA significantly attenuated increases in waist circumference ( P for trend TV viewing time change was not significantly associated with changes in waist circumference ( P for trend = 0.06 ) . Combined categories of MVPA and TV viewing time changes were predictive of waist circumference increases ; compared with those who increased MVPA and reduced TV viewing time , those who reduced MVPA and increased TV viewing time had a 2-cm greater increase in waist circumference ( P = 0.001 ) . Conclusion Decreasing MVPA emerged as a significant predictor of increases in waist circumference . Increasing TV viewing time was also influential , but its impact was much weaker than MVPA", "OBJECTIVE : Since the prevalence of adult obesity is increasing in the United States , we examined the effect of changing common habits ( exercise , TV viewing , smoking and eating habits ) on four year change in body weight . DESIGN : A prospect i ve cohort study of US male health professionals with follow-up from 1988–1992 . Participants were 19 478 men aged 40–75 in 1986 , who were free of cancer , coronary heart disease , stroke and diabetes . METHODS : Multiple regression was used to determine the association between four year change in body weight ( from 1988–1992 ) and common habits , after adjusting for baseline age , hypertension and hypercholesterolemia . RESULTS : For middle aged men , vigorous activity was associated with weight reduction and TV/VCR viewing and eating between meals with weight gain . Quitting smoking and a history of voluntary weight loss prior to the study period were consistently related to weight increase . Recently being on a diet was more strongly associated with weight loss among older men . Over the four year follow-up period , middle-aged men who increased their exercise , decreased TV viewing and stopped eating between meals , lost an average weight of −1.4 kg ( 95 % confidence interval (CI)−1.6 – −1.1 kg ) , compared to a weight gain of 1.4 kg among the overall population . The prevalence of obesity among middle-aged men was lowest among those who maintained a relatively high level of vigorous physical activity , compared to those who were relatively sedentary . CONCLUSION : These data suggest that improvement in the mix of health habits , particularly increasing vigorous activity , as well as decreasing TV use and changing eating habits , results in weight maintenance or a modest weight loss over four years", "OBJECTIVE : To examine long-term effects of leisure time physical activity ( ltpa ) and occupational physical activity ( opa ) on later obesity , and to examine the effect of body weight on later physical inactivity in men with and without juvenile onset obesity . DESIGN : Population -based longitudinal study of obese and nonobese men , who were identified as draftees of median age of 19 y in 1943–77 and later examined at general health surveys in 1982–84 , and in 1991–93 . SETTING : Copenhagen and adjacent regions , Denmark . PARTICIPANTS : In all , 1143 juvenile obese men with a BMI ≥31 kg/m2 ( corresponding to 35 % overweight by an originally used national st and ard ) at draft board examination , and , as a nonobese control group , 1278 men selected as a 0.5 % r and om sample of the approximately 255 600 men examined at the draft board and thus representing the study population .MAIN OUTCOME MEASURES : Obesity , defined as BMI ≥30 kg/m2 , and physical inactivity at the last survey . RESULTS : In the cross-sectional analyses , there were strong concurrent inverse associations between ltpa and prevalence of obesity in both groups , whereas there was no relation to opa . In logistic regression analyses of obesity at the last survey , including both ltpa and opa as well as age , BMI at draft board examination , BMI at first follow-up , length of education , smoking and drinking habits , there were no significant effects of ltpa and opa on the risk of development of obesity in the nonobese group or maintenance of obesity in the obese group . Similar analyses of physical inactivity at the last follow-up as outcome showed a significant direct effect of BMI at first follow-up , with a significant trend in the nonobese group , but not in the obese group and no effects on opa . CONCLUSION : There is no long-term influence of physical activity on development and maintenance of obesity in men , whereas greater body weight increases risk of later physical inactivity during leisure time", "OBJECTIVE To examine the role of television ( TV ) viewing in long-term maintenance of weight loss . RESEARCH METHODS AND PROCEDURES All subjects ( N = 1422 ) were enrolled in the National Weight Control Registry ( NWCR ) , a national sample of adults who have maintained a minimum weight loss of 13.6 kg for at least 1 year . Participants self-reported the average number of hours of weekly TV viewing at entry into the NWCR and at a 1-year follow-up . Cross-sectional and prospect i ve analyses were performed to determine the frequency of TV viewing and the extent to which TV viewing was independently associated with weight regain over the 1-year of follow-up . RESULTS A relatively high proportion ( 62.3 % ) of participants reported watching 10 or fewer hours of TV per week on entry in the NWCR . More than one third of the sample ( 36.1 % ) reported watching or = 21 h/wk , which contrasts markedly from the national average of 28 hours of TV viewing per week reported by American adults . Both baseline TV viewing ( p in TV viewing ( p 1-year weight regain , independent of physical activity and dietary behaviors . DISCUSSION Individuals who are successful at maintaining weight loss over the long term are likely to spend a relatively minimal amount of time watching TV", "OBJECTIVE To determine whether interrupting prolonged sitting with brief bouts of light-intensity walking ( LW ) or simple resistance activities ( SRA ) improves postpr and ial cardiometabolic risk markers in adults with type 2 diabetes ( T2D ) . RESEARCH DESIGN AND METHODS In a r and omized crossover trial , 24 inactive overweight/obese adults with T2D ( 14 men 62 ± 6 years old ) underwent the following 8-h conditions on three separate days ( with 6–14 days washout ) : uninterrupted sitting ( control ) ( SIT ) , sitting plus 3-min bouts of LW ( 3.2 km · h−1 ) every 30 min , and sitting plus 3-min bouts of SRA ( half-squats , calf raises , gluteal contractions , and knee raises ) every 30 min . St and ardized meals were consumed during each condition . Incremental areas under the curve ( iAUCs ) for glucose , insulin , C-peptide , and triglycerides were compared between conditions . RESULTS Compared with SIT , both activity-break conditions significantly attenuated iAUCs for glucose ( SIT mean 24.2 mmol · h · L−1 [ 95 % CI 20.4–28.0 ] vs. LW 14.8 [ 11.0–18.6 ] and SRA 14.7 [ 10.9–18.5 ] ) , insulin ( SIT 3,293 pmol · h · L−1 [ 2,887–3,700 ] vs. LW 2,104 [ 1,696–2,511 ] and SRA 2,066 [ 1,660–2,473 ] ) , and C-peptide ( SIT 15,641 pmol · h · L−1 [ 14,353–16,929 ] vs. LW 11,504 [ 10,209–12,799 ] and SRA 11,012 [ 9,723–12,301 ] ) ( all P was significantly attenuated for SRA ( P CONCLUSIONS Interrupting prolonged sitting with brief bouts of LW or SRA attenuates acute postpr and ial glucose , insulin , C-peptide , and triglyceride responses in adults with T2D . With poor adherence to structured exercise , this approach is potentially beneficial and practical", "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", "OBJECTIVE Sedentary behaviour may be a contributor to weight gain in today 's young adult women , who are gaining weight faster than women in their mothers ' generation . The aim was to examine the relationships between sitting time and weight in young women . METHOD Data were from women born in 1973 - 1978 who completed surveys in 2000 , 2003 and 2006 for the Australian Longitudinal Study on Women 's Health . Associations between concurrent changes in sitting-time and weight , and prospect i ve associations between these variables , were examined using ANOVA and linear regressions , stratified by BMI -category in 2000 ( n=5562 ) . RESULTS Among overweight and obese women , percentage weight change from 2000 to 2006 was higher in those whose sitting time increased ( > 20 % ) than in those whose sitting time decreased ( > 20 % ) over the same period ( p percentage change in sitting time was significantly higher in those who gained weight ( > 5 % ) than in those who lost weight ( > 5 % ) ( p change in ) sitting time and weight change , or between ( change in ) weight and change in sitting time . CONCLUSION The results confirm associations between concurrent changes in weight and changes in sitting time in overweight and obese women , but no prospect i ve relationships were found", "BACKGROUND Identifying strategies to increase energy expenditure ( EE ) may help combat the harmful effects of sedentary behavior . This study examined EE during sitting , st and ing , and walking . METHODS Participants ( N = 74 ) were r and omized to 2 of the following activities : sitting using a laptop computer ( SIT-C ) , sitting watching television ( SIT-T ) , st and ing watching television ( ST AND ) , and walking at a self-selected pace ≤3.0 ( mph ) ( WALK ) . Each activity lasted 15 minutes with a 3-minute transition period between activities . The experimental conditions were : SIT-C to ST AND ( N = 18 ) , SIT-T to WALK ( N = 18 ) , ST AND to SIT-C ( N = 20 ) , and WALK to SIT-T ( N = 18 ) . EE was measured using indirect calorimetry . RESULTS Based on the first activity performed , EE during WALK ( 55.92 ± 14.19 kcal ) was significantly greater than SIT-C ( 19.63 ± 6.90 kcal ) , SIT-T ( 18.66 ± 4.01 kcal ) , and ST AND ( 21.92 ± 5.08 kcal ) ( P in SIT-T to WALK ( 74.50 ± 17.88 kcal ) and WALK to SIT-T ( 82.72 ± 21.70 kcal ) was significantly greater than EE in SIT-C to ST AND ( 45.38 ± 14.78 kcal ) and ST AND to SIT-C ( 45.64 ± 9.69 kcal ) ( P of sitting or st and ing with walking significantly increases EE , but substituting periods of sitting with st and ing may not affect EE . Thus , the potential benefits of st and ing as opposed to sitting need further investigation beyond the role of EE", "BACKGROUND Traditional desks require students to sit ; however , recently schools have provided students with nontraditional st and ing desks . The purpose of this study was to investigate differences in caloric expenditure of young adults while sitting at a st and ard classroom desk and st and ing at a nontraditional st and ing classroom desk . METHODS Twenty ( 10 male/10 female ) young ( 22.8 ± 1.9 y ) , healthy participants reported to the laboratory between the hours of 7:00 AM and 2:00 PM following a 12-h fast and 48-h break in exercise . Participants were r and omly assigned to perform a series of mathematical problems either sitting at a normal classroom desk or st and ing at a nontraditional st and ing desk . Inspired and expired gases were collected for 45-min for the determination of oxygen consumption ( VO2 ) , carbon dioxide production ( VCO2 ) , and minute ventilation ( VE ) using a metabolic gas system . RESULTS There were significant increases from sitting to st and ing in VO2 ( 0.22 ± 0.05 vs. 0.28 ± 0.05 L·min-1 , P ≤ .0001 ) , VCO2 ( 0.18 ± 0.05 vs. 0.24 ± 0.050 L·min-1 , P ≤ .0001 ) , VE ( 7.72 ± 0.67 vs. 9.41 ± 1.20 L·min-1 , P ≤ .0001 ) , and kilocalories expended per minute ( 1.36 ± 0.20 kcal/min , P ≤ .0001 vs. 1.02 ± 0.22 kcal/min , P ≤ .0001 ) . CONCLUSIONS Results indicate a significant increase in caloric expenditure in subjects that were st and ing at a st and ing classroom desk compared with sitting at a st and ard classroom desk", "BACKGROUND Compared with prolonged sitting , regular activity breaks immediately lower postpr and ial glucose and insulin , but not triglyceride responses . Postpr and ial triglycerides can be lowered by physical activity but the effect is often delayed by ∼12 to 24 hours . OBJECTIVE The objective of the study was to determine whether regular activity breaks affect postpr and ial triglyceride response in a delayed manner similar to physical activity . METHODS In a r and omized crossover trial , 36 adults ( body mass index 23.9 kg/m2 [ st and ard deviation 3.9 ] ) completed four 2-day interventions : ( 1 ) prolonged sitting ( SIT ) ; ( 2 ) prolonged sitting with 30 minutes of continuous walking ( 60 % VO2max ) , at the end of Day 1 ( SIT + PAD1 ) ; ( 3 ) Sitting with 2 minutes of walking ( 60 % VO2max ) every 30 minutes ( RAB ) ; ( 4 ) A combination of the continuous walking and regular activity breaks in 2 and 3 above ( RAB + PAD1 ) . Postpr and ial plasma triglyceride , nonesterified fatty acids , glucose , and insulin responses were measured in venous blood over 5 hours on Day 2 . RESULTS Compared with SIT , both RAB ( difference : -43.61 mg/dL·5 hours ; 95 % confidence interval [ CI ] -83.66 to -2.67 ; P = .035 ) and RAB + PAD1 ( -65.86 mg/dL·5 hours ; 95 % CI -112.14 to -19.58 ; P = .005 ) attenuated triglyceride total area under the curve ( tAUC ) . RAB + PAD1 produced the greatest reductions in insulin tAUC ( -23 % ; 95 % CI -12 % to -31 % ; P largest increase in nonesterified fatty acids ( tAUC , 10.08 mg/dL·5 hours ; 95 % CI 5.60 - 14.84 ; P ) . There was no effect on glucose tAUC ( P = .290 ) . CONCLUSIONS Postpr and ial triglyceride response is attenuated by regular activity breaks , when measured ∼24 hours after breaks begin . Combining regular activity breaks with 30 minutes of continuous walking further improves insulinemic and lipidemic responses " ]

[ "Objective To evaluate the shear bond strength of precoated orthodontic brackets bonded with self-etching primer relative to that of noncoated conventionally-bonded brackets at two different time intervals . Methods Twenty-one subjects were selected for r and omized split-mouth bonding of two types of brackets to the maxillary arch . Half of the teeth had precoated brackets bonded using self-etching adhesive , and the other half had regular brackets bonded using Transbond XT adhesive . Nitinol wires were tied to the upper arch and were left until the time of debonding . The patients were r and omly divided into two groups : one debonded after one hour and the other debonded two weeks after the initial wire placement . The shear bond strength was directly recorded from the patients ’ mouths using an in vivo debonding device . Results There were no significant differences in shear bond strength between the precoated and conventional groups or within each group at different time intervals . There were significant differences between anterior and posterior teeth in both the precoated and conventional groups . Conclusion Pre-coated brackets bonded with self-etching adhesive have the same bonding strength as the conventionally bonded brackets", "The purpose of the present study was to test a new in vivo debonding device and compare in vivo bond strengths recorded by this device with in vitro bond strengths recorded by a universal testing machine such as the Instron . For the in vitro part of the study , 60 extracted premolar teeth were divided into 2 groups of 30 each . Both groups of 30 teeth had 3 M Unitek Victory Twin brackets , precoated with Transbond XT composite resin , bonded to them . Shear bond strength tests were carried out in vitro using the universal testing machine on one group of 30 teeth while the debonding device was used on the other group of 30 teeth . The mean shear bond strength of the group debonded using the universal machine was 11.02 MPa and that of the group debonded with the debonding device was 12.82 MPa . For the in vivo part of the study , 8 patients r and omly assigned to the research clinician from patients in The University of Alabama School of Dentistry , Department of Orthodontics , had a total of 60 premolar teeth bonded with 3 M Unitek Victory Twin brackets . Following comprehensive orthodontic treatment ( average time of 23 months ) , shear bond strength tests were carried out using the debonding device , which can measure debonding forces in vivo . The mean shear bond strength recorded in vivo was 5.47 MPa . Statistically significant differences were found between all 3 groups tested . The results appear to indicate that mean bond strengths recorded in vivo following comprehensive orthodontic treatment are significantly lower than bond strengths recorded in vitro", "The aim of this study was to evaluate the influence of a self-etching primer ( SEP ) ( Transbond Plus SEP , 3 M Unitek , Monrovia , Calif ) on shear bond strength of adhesive uncoated and precoated Victory brackets ( 3 M Unitek ) . The sample group consisted of 23 patients , with four premolars each , equally divided in four different groups . Brackets were bonded in vivo by the same operator using a split-mouth r and om technique : group 1 , 37 % phosphoric acid + primer + composite + conventional Victory bracket ; group 2 , 37 % phosphoric acid + primer + precoated Victory bracket ; group 3 , SEP + composite + conventional bracket ; group 4 , SEP + precoated bracket . After 30 days , premolars were extracted for orthodontic reasons and a Universal Instron Machine was used to apply an occlusal shear force directly to the enamel-bracket interface at a speed of 0.5 mm/min . The groups were compared using two-way analysis of variance . Mean results and st and ard deviation for the groups were : group 1 = 11.60 + /- 2.65 Mpa , group 2 = 9.79 + /- 2.71 Mpa , group 3 = 10.75 + /- 2.67 Mpa , and group 4 = 10.31+/- 2.70 Mpa . No difference was observed between the conventional etching and primer or SEP ( P = .948 ) . However , significant differences in bond strength were present between the uncoated and precoated brackets ( P = .032 ) . Considering the values required to withst and normal orthodontic forces ( 8 - 9 Mpa ) , it could be concluded that the SEP combined with adhesive precoated brackets showed adequate shear bond strength and may be suitable for clinical use", "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", "The purpose of this study was to evaluate the shear bond strengths of a composite resin ( Transbond XT ; 3M/Unitek , Monrovia , Calif ) and a resin-modified glass ionomer ( Fuji Ortho LC ; GC America Inc , Alsip , Ill ) cured with 2 different light-curing units : a conventional visible light unit ( Ortholux XT ; 3 M Dental Products , St Paul , Minn ) and a xenon arc light unit ( Plasma Arc Curing [ PAC ] System ; American Dental Technologies , Corpus Christi , Texas ) . One hundred twenty freshly extracted bovine permanent m and ibular incisors were r and omly divided into 1 of 8 groups ; each group consisted of 15 specimens . Two groups ( 1 group for each type of adhesive ) were exposed to the visible light for 20 seconds ( Transbond XT ) and 40 seconds ( Fuji Ortho LC ) , respectively , and used as control groups . The remaining 6 groups ( 3 for each adhesive ) were cured with the xenon arc light for 2 , 5 , and 10 seconds . After bonding , all sample s were stored in distilled water at room temperature for 24 hours and subsequently tested in a shear mode on an Instron universal testing machine ( Instron Corp , Canton , Mass ) . For the groups bonded with Transbond XT , no statistically significant differences ( P = .868 ) were found between the shear bond strength of the control group cured with Ortholux XT and those of the groups cured with the PAC System for 2 , 5 , or 10 seconds . When the shear bond strengths of the groups bonded with Fuji Ortho LC were evaluated , no statistically significant differences ( P = .087 ) were found between the control group that was cured with Ortholux XT and those cured with the PAC System . The bond strength of the composite resin was significantly higher than that of the resin-modified glass ionomer in all the groups tested ( P light-curing , the xenon arc light enables the clinician to significantly reduce the curing time of both bonding agents , without affecting their shear bond strengths . Therefore , xenon arc light sources can be recommended as an advantageous alternative for curing both composite resins and resin-modified glass ionomers", "Bracket debonding strength related to diverse debonding methods and enamel damage has not been assessed in vivo . The study hypothetized a direct relationship between these three parameters . Debonding strength was measured clinical ly in the wings method and base method on 50 patients in a split mouth method using a calibrated debonding plier . Brackets from 30 of these patients were scanned in SEM and EDAX for adhesive remnant index and enamel calcium remnants . Base method debonding force was significantly greater than wings method ( 163.5+/-68.7 N , 106.1+/-66.2 N , respectively , p positive adhesive remnant index score was found in both methods ( 68.7 % , 66.7 % , respectively ) . Debonding strength vs. adhesive remnant index or calcium index scores were not correlated . However , the latter two were significantly correlated ( 0.524 debonding failures developed at the adhesive enamel interface . The results warnts the potential of enamel damage during debonding", "INTRODUCTION Many advantages of argon lasers have been reported , including high-speed orthodontic adhesive curing and less enamel demineralization . The purpose of this study was to compare bond strengths after curing with the argon laser ( 10 seconds ) and the conventional curing light ( 40 seconds ) in vivo and in vitro . METHODS Four premolars from each of 23 volunteers were r and omly assigned to either the argon laser group or the conventional light group for the in-vivo study . Shear bond strengths were measured after 14 days with custom- design ed debonding pliers . In-vitro bond strengths were measured by using 4 premolars from each of 25 volunteers . Shear bond strength was measured after 14 days of thermocycling with the same protocol as the in-vivo study . Adhesive remnant index scores ( ARI ) were determined . RESULTS No significant differences were found in bond strengths according to curing method , dental arch , or sex . In-vivo results were significantly lower ( P ARI scores between the curing methods was determined ; no significant correlation between mean bond strengths and ARI scores was determined . CONCLUSIONS Bond strength for argon laser curing is comparable to conventional light curing and is sufficient for clinical applications . Although the argon laser left more adhesive on the tooth surfaces on debonding , there was no increase in enamel surface fractures", "OBJECTIVE The purpose of the present study was to analyze the influence of debonding force location in shear bond strength testing of orthodontic brackets in vitro . METHODS Ninety extracted permanent bovine m and ibular incisors were r and omly divided into 3 groups of 30 specimens each . Teeth were bonded with stainless steel orthodontic brackets . Enamel surfaces were etched with 37 % phosphoric acid for 30s and bonded with a composite adhesive . Debonding force measurements were performed with a universal testing machine . Location of the debonding force was : bracket base ( group A ) , ligature groove ( group B ) , occlusal bracket wings ( group C ) . RESULTS Mean shear bond strength measurements were as follows : 22.70(4.23)MPa ( group A ) , 11.52(2.74)MPa ( group B ) , 9.44(2.96)MPa ( group C ) . Analysis of variance indicated that there were significant differences in shear bond strength . Post-hoc Tukey tests showed that bond strength measurements of group A were significantly different from those of groups B and C. The adhesive remnant index also showed significant differences and ranged from a mean of 1.53 in group A to a mean of 2.10 in group C. SIGNIFICANCE Debonding force location had a significant influence on shear bond strength measurements and bond failure pattern , indicating that this parameter needs to be taken into consideration for inter study comparison of in vitro results" ]

[ "1 . In adult humans with growth hormone deficiency , treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance . The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone ( 0.07 units/kg at night ) in a double-blind , placebo-controlled trial lasting 6 months . 2 . Compared with placebo , resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone . No differences were noted between the groups with respect to left ventricular end-systolic dimension , fractional shortening , wall thicknesses or mean arterial blood pressure . Left ventricular myocardial mass increased in the group given recombinant human growth hormone . 3 . The supine plasma renin activity was increased and remained elevated over the 6 months , whereas the plasma aldosterone concentration was unchanged , after treatment with recombinant human growth hormone . Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone . 4 . We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency result ed in small increases in left ventricular pre-load , due to the sodium-retaining action of growth hormone . Activation of the renin-aldosterone system was involved in such changes . Myocardial hypertrophy was observed without changes in mean arterial pressure , reflecting the anabolic action of growth hormone", "OBJECTIVES The goal of this study was to determine the predictive value of pregnancy-associated plasma protein-A ( PAPP-A ) in patients with acute coronary syndromes ( ACS ) . BACKGROUND Pregnancy-associated plasma protein-A is a zinc-binding matrix metalloproteinase abundantly expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization . METHODS In 547 patients with angiographically vali date d ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain , respectively , PAPP-A as well as markers of myocardial necrosis ( troponin T [ TnT ] ) , ischemia ( vascular endothelial growth factor [ VEGF ] ) , inflammation ( high-sensitivity C-reactive protein [ hsCRP ] ) , anti-inflammatory activity ( interleukin [IL]-10 ) , and platelet activation ( soluble CD40 lig and [ sCD40L ] ) were determined . Patients were followed for the occurrence of death or myocardial infa rct ion . RESULTS In patients with ACS , elevated PAPP-A levels ( > 12.6 mIU/l ) indicated an increased risk ( odds ratio 2.44 [ 95 % confidence interval ( CI ) 1.43 to 4.15 ] ; p = 0.001 ) . When the analysis was restricted to TnT-negative patients , PAPP-A still identified a subgroup of high-risk patients ( odds ratio [ OR ] 2.72 [ 95 % confidence interval ( CI ) 1.25 to 5.89 ] ; p = 0.009 ) . In a multivariable model , PAPP-A ( OR 2.01 ; p = 0.015 ) , sCD40L ( OR 2.37 ; p = 0.003 ) , IL-10 ( OR 0.43 ; p = 0.003 ) , and VEGF ( OR 2.19 ; p = 0.018 ) were independent predictors . Prospect i ve validation in patients with chest pain confirmed that PAPP-A levels reliably identify high-risk patients ( adjusted OR 2.32 [ 95 % CI 1.32 to 4.26 ] ; p = 0.008 ) . Patients negative for all three markers ( TnT , sCD40L , and PAPP-A ) were at very low cardiac risk ( 30 days : 3.0 % event rate ; no death ) . CONCLUSIONS The PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS . Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS", "CONTEXT Data regarding effects of lower-dose GH on cardiopulmonary function in GH-deficient ( GHD ) adults are limited . OBJECTIVES The objective was to assess effects of lower-dose GH on exercise capacity and echocardiographic parameters in GHD adults . DESIGN The study was a 6-month double-blind , placebo-controlled r and omized trial . SETTING The study was conducted at the General Clinical Research Center . PARTICIPANTS Thirty hypopituitary adults with GHD were studied . INTERVENTION Subjects were r and omized to recombinant human GH or placebo for 6 months , followed by open-label recombinant human GH for 12 months . MAIN OUTCOME MEASURES Primary endpoints were exercise duration , maximal oxygen consumption , and left ventricular ejection fraction . Secondary endpoints were echocardiographic indices of systolic and diastolic function , left ventricular mass , lipids , and body composition . RESULTS In the 6-month double-blind phase , mean GH dose was 0.64 mg/d . Mean IGF-I sd score increased from -4.5 to -1.0 . Exercise duration , maximal oxygen consumption , left ventricular ejection fraction , and other echocardiographic parameters were normal at baseline and did not change . GH decreased total and low-density lipoprotein cholesterol by 7.5 % ( P = 0.016 ) and 14.7 % ( P = 0.002 ) ( P = 0.04 vs. placebo ) . Mean lean body mass increased by 2.2 kg ( P = 0.004 ) , fat mass decreased by 1.7 kg ( P = 0.21 ) , and percent body fat decreased by 2.5 % ( P = 0.018 ) , although between-group changes were not significant . CONCLUSIONS Human GH did not improve exercise performance or echocardiographic parameters or decrease fat mass but significantly decreased total and low-density lipoprotein cholesterol , increased IGF-I , and increased lean body mass . These results indicate that responses to human GH are variable and should be assessed at baseline and during treatment", "The onset of adult GH deficiency may be during either adulthood ( AO ) or childhood ( CO ) , but potential differences have not previously been examined . In this study the baseline and GH therapy ( 12.5 micrograms/kg per day ) data from CO ( n = 74 ; mean age 29 yr ) and AO ( n = 99 ; mean age 44 yr ) GH-deficient adult patients have been compared . The first 6 months comprised r and omized , double-blind treatment with GH or placebo , then all patients were GH-treated for a further 12 months . At baseline the height , body weight , body mass index , lean body mass , and waist/hip ratio of AO patients were significantly ( P Serum insulin-like growth factor-I ( IGF-I ) levels were below normal but were lower in CO than AO patients ( P Osteocalcin concentration in CO patients was above the normal range and significantly greater than in AO patients . Both groups had significant psychosocial distress , but the deviation from normality was greater in AO patients . Throughout GH therapy there was a significant increase in lean body mass and significant decrease in percent body fat and sum of skinfolds in each group . Wais/hip ratio was decreased by long-term therapy in AO but not CO patients . Total and low density lipoprotein cholesterol levels were decreased from baseline at 6 months in AO but not CO patients and high density lipoprotein cholesterol was increased in both groups throughout therapy . IGF-I and IGF binding protein-3 were increased into the normal range by GH therapy in both groups . Mean osteocalcin level in AO patients was increased at 6 months with no further change with GH therapy , whereas in CO patients there was a steep increase up to 12 months but then a sharp decrease . Nottingham Health Profile scores showed significant improvements in physical mobility and energy at 18 months of therapy in AO patients but no consistent effects in CO patients . GH-induced side effects were mainly reported by AO patients ; very few CO patients reported treatment-emergent adverse events . These results demonstrate significant differences in clinical and biochemical presentation and responses to therapy of the adult GH deficiency syndrome . This is consistent with the existence of two entities , developmental ( CO ) and metabolic ( AO ) , and the different functions of GH at different periods of life", "Objective Adult onset GH deficiency ( GHD ) is characterized by abnormalities of serum lipoprotein profiles and GH replacement results in favourable alterations in serum total and low density lipoprotein (LDL)‐cholesterol . Preliminary evidence has indicated that the effect of GH replacement in this respect may be additive to that of HMG CoA reductase inhibitor ( statin ) therapy . We have examined this possibility during prospect i ve follow‐up of adult onset hypopituitary patients enrolled in KIMS ( Pfizer International Metabolic Data base ) , a pharmacoepidemiological study of GH replacement in adult hypopituitary patients", "Objective Few studies have determined the effects of more than 5–10 years of GH replacement in adults on body composition and cardiovascular risk factors . Design / patients In this prospect i ve , single-center , open-label study , the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults ( 93 men ) with adult-onset GH deficiency ( GHD ) . Mean age was 50.5 ( range 22–74 ) years at study start . Body composition was measured using dual-energy X-ray absorptiometry . Results The mean initial GH dose of 0.55 ( s.e.m . 0.03 ) mg/day was gradually lowered to 0.40 ( 0.01 ) mg/day after 15 years . The mean serum IGF1 SDS increased from −1.53 ( 0.10 ) at baseline to 0.74 ( 0.13 ) at study end ( P baseline ) . Lean soft tissue ( LST ) increased to 3 % above the baseline level at study end ( P vs baseline ) , body fat ( BF ) started to increase and had returned to the baseline level after 15 years . Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased . Fasting plasma glucose increased from 4.4 ( 0.1 ) at baseline to 4.8 ( 0.1 ) mmol/l at study end ( P ) . However , blood HbA1c decreased from 5.0 ( 0.1 ) to 4.6 ( 0.1 ) % ( P GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile . Fasting plasma glucose increased whereas blood HbA1c was reduced", "Assessed by conventional echocardiography the influence of growth hormone deficiency ( GHD ) and effects of replacement therapy on left ventricle ( LV ) function and mass ( LVM ) have shown inconsistent results . We aim ed to evaluate cardiac function before and during replacement therapy employing the gold st and ard method cardiac magnetic resonance imaging ( CMRI ) and measurements of circulating levels of B-type natriuretic peptides . Sixteen patients ( 8 males and 8 females , mean age 49 years ( range 18–75 ) ) with severe GHD and 16 matched control subjects were included . CMRI was performed at baseline and after 1 year of GH replacement therapy . IGF-I , B-type natriuretic peptide ( BNP ) and N-terminal pro-BNP ( NT-proBNP ) were measured after 0 , 1 , 2 , 3 , 6 and 12 months of treatment . IGF-I Z-score increased from ( median ( IQR ) ) −2.3 ( −3.8 to −1.4 ) to 0.5 ( −0.3 to 1.7 ) . LVM index ( LVMI ) , ejection fraction ( range 63–80 % ) , cardiac output index and levels of BNP and NT-proBNP were similar at baseline in patients compared to controls ( P-values from 0.09 to 0.37 ) . The patients had significantly smaller LV end-diastolic volume index ( P = 0.032 ) and end-systolic volume index ( P = 0.038 ) . No significant change in LV systolic function or LVM occurred during 1 year of GH treatment . BNP levels were unchanged ( P = 0.88 ) , whereas NT-proBNP tended to decrease ( P = 0.052 ) . Assessed by the highly sensitive and precise CMRI method , untreated GHD was not associated with impaired systolic function or reduced LVMI and 1 year of GH replacement using physiological doses did not influence cardiac mass or function", "BACKGROUND Four retrospective studies have reported premature mortality in patients with hypopituitarism with st and ard mortality ratios ( SMRs ) varying between 1.20 and 2.17 . Patients with hypopituitarism have complex endocrine deficiencies , and the mechanisms underpinning any excess mortality are unknown . Furthermore , the suggestion has emerged that endogenous growth-hormone deficiency might account for any excess mortality . We aim ed to clarify these issues by doing a large prospect i ve study of total and specific-cause mortality in patients with hypopituitarism . METHODS We followed up 1014 UK patients ( 514 men , 500 women ) with hypopituitarism from January , 1992 , to January , 2000 . 573 ( 57 % ) patients had non-functioning adenomas , 118 ( 12 % ) craniopharyngiomas , and 93 ( 9 % ) prolactinomas . SMRs were calculated as the ratio of observed deaths to the number of deaths in an age-matched and sex-matched UK population . FINDINGS The number of observed deaths was 181 compared with the 96.7 expected ( SMR 1.87 [ 99 % CI 1.62 - 2.16 ] , p Univariate analysis indicated that mortality was higher in women ( 2.29 [ 1.86 - 2.82 ] ) than men ( 1.57 [ 1.28 - 1.93 ] , p=0.002 ) , in younger patients , in patients with an underlying diagnosis of craniopharyngioma ( 9.28 [ 5.84 - 14.75 ] vs 1.61 [ 1.30 - 1.99 ] , p Excess mortality was attributed to cardiovascular ( 1.82 [ 1.30 - 2.54 ] , p respiratory ( 2.66 [ 1.72 - 4.11 ] , p cerebrovascular ( 2.44 [ 1.58 - 4.18 ] , p mortality , except for gonadotropin deficiency , which , if untreated was associated with excess mortality ( untreated 2.97 [ 2.13 - 4.13 ] vs treated 1.42 [ 0.97 - 2.07 ] , p Patients with hypopituitarism have excess mortality , predominantly from vascular and respiratory disease . Age at diagnosis , female sex , and above all , craniopharyngioma were significant independent risk factors . Specific endocrine-axis deficiency , with the exception of untreated gonadotropin deficiency , does not seem to have a role", "BACKGROUND Adult GHD syndrome is associated with clustering of adverse cardiovascular ( CV ) risk factors such as abnormal body composition , dyslipidemia , insulin resistance and abnormal haemostatic factors . There is a wealth of evidence linking CV events with elevated levels of inflammatory markers ( hs-CRP and IL-6 ) in the general population ; however data on their abnormalities in GHD and specially the effects of GH replacement ( GHR ) on these inflammatory markers are limited . OBJECTIVE To study the effects of GHR on inflammatory markers , glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease . DESIGN Fifteen hypopituitary adults ( 11 males , mean age 48.5 years ) with recently diagnosed , severe GHD were recruited . Patients received GHR ( in addition to other pituitary hormone replacements ) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels . Weight , waist hip ratio ( WHR ) , body composition , fasting plasma glucose and insulin , insulin resistance index ( HOMA-IR ) , fasting serum lipid levels , hs-CRP , IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR . RESULTS GHR result ed in a physiological increase in IGF-1 SDS [ median -0.6 to + 0.39 , P improved quality of life ( mean pre-treatment AGHDA score 16 vs. post-treatment score 7 , P reduction in WHR ( 0.94 vs. 0.92 , P=0.01 ) . There were no significant changes in body weight and composition . Levels of hs-CRP ( log transformed , mean ( SD ) ) were significantly reduced following GHR ( pre 1.21 ( 0.9 ) vs. post 0.27 ( 0.9 ) , P TNF-alpha and IL-6 levels remained unchanged . Fasting glucose ( mmol/L ) [ 4.6 ( 0.1 ) vs. 5.1 ( 0.1 ) , P=0.003 ] , fasting insulin ( muU/mL ) [ 9.4 ( 8.1 ) vs. 12.1 ( 9.2 ) , P=0.03 ] and HOMA-IR [ 1.2 ( 1.0 ) vs. 1.5 ( 1.1 ) P=0.02 ] ( all pre-GHR vs. post-GHR and mean ( SD ) ) significantly increased following GHR indicating increased insulin resistance . Significant improvements were noted in fasting LDL-cholesterol ( LDL-C ) and HDL-cholesterol ( HDL-C ) levels following GHR [ 3.4 ( 0.9 ) vs. 2.9 ( 0.7 ) , P=0.03 and 1.2 ( 0.2 ) vs. 1.3 ( 0.2 ) , P=0.02 , respectively ] ( all pre-GHR vs. post-GHR and mean ( SD ) ) . Levels of total cholesterol and triglycerides did not change following GHR . CONCLUSIONS Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD result ed in favourable changes in hs-CRP , WHR , fasting LDL-C and HDL-C levels all of which are recognised CV risk markers . However , there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR , monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population", "CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and C-reactive protein ( CRP ) are associated with development of type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P and CRP ( P relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis", "BackgoundThrombosis is regarded to be a key factor in the development of acute coronary syndromes in patients with coronary artery disease ( CAD ) . We hypothesize , that hemostatic and rheological risk factors may be of major relevance for the incidence and the risk stratification of these patients . Methods In 243 patients with coronary artery disease and stable angina pectoris parameters of metabolism , hemostasis , blood rheology and endogenous fibrinolysis were assessed . Patients were prospect ively followed for 2 years in respect to elective revascularizations and acute coronary syndromes . Results During follow-up 88 patients presented with cardiac events , 22 of those were admitted to the hospital because of acute events , 5 Patients were excluded due to non- cardiac death . Patients with clinical events were found to be more frequently diabetic and presented with a more progressed coronary atherosclerosis . Even though patients with diabetes mellitus demonstrated a comparable level of multivessel disease ( 71 % vs. 70 % ) the rate of elective revascularization was higher ( 41 % vs. 28 % , p incidence of acute cardiovascular events ( 18 % vs. 8 % , p levels of fibrinogen ( 352 ± 76 vs. 312 ± 64 mg/dl , p ( 1.38 ± 0.23 vs. 1.31 ± 0.16 mPas , p ( 13.2 ± 2.5 vs. 12.1 ± 3.1 E , p Pathological alterations of fibrinogen , blood rheology and plasminogen-activator-inhibtor as indicators of a procoagulant state are of major relevance for the short-term incidence of cardiac events , especially in patients with diabetes mellitus type 2 , and may be used to stratify patients to specific therapies", "The effects of GH replacement on body fat composition and insulin sensitivity were assessed in GH-deficient adults . The patients were r and omized into a double-blind , placebo-controlled study of human recombinant GH replacement therapy for 6 months ( period 1 ) , followed by an open phase of GH for another 6 months ( period 2 ) . Anthropometric variables , body fat composition ( fat % ) , and biochemical parameters were measured during the trial . Measurements of in vivo insulin sensitivity were carried out at the commencement of the study and on completion of the trial by modified insulin suppression test . The modified insulin suppression test was performed both in the morning ( AM ) and in the afternoon ( PM ) to further evaluate the PM-AM steady-state plasma glucose ( SSPG ) pattern . We found that the GH-deficient adults had more body fat and were insulin resistant . Significant reduction in fat % and total body fat mass was found in the active arm of period 1 without alteration of body weight . Besides , we demonstrated , for the first time , the GH replacement for 6 months did not alter the insulin sensitivity , but replacement for a longer period ( 12 months ) normalized not only the AM SSPG level but also the PM-AM SSPG pattern . We also found a positive correlation between SSPG ( regardless of AM vs. PM ) and fat % and total body fat mass . In conclusion , normalization of insulin sensitivity in GH-deficient adults after replacement of GH may be related to the reduction of total body fat", "Short-term studies of GH replacement in adult hypopituitarism have usually demonstrated beneficial effects on body composition and circulating lipids , with neutral or occasionally adverse effects on glucose tolerance . Fasting hyperinsulinemia has been reported . GH effects on cardiac function have been variable . The effects of long-term GH therapy , taking into account the consequences of increasing age , are not fully known . Thirty-three hypopituitary , initially middle-aged adults were studied over a 7-yr period ; 12 patients took GH therapy ( mean , 0.7 mg daily ) continuously ( group A ) ; 11 took GH for only 6 - 18 months , a minimum of 5 yr previously ( group B ) ; and 10 patients never received GH therapy ( group C ) . Other pituitary replacement was maintained . Effects on anthropometry , body composition ( by bioimpedance analysis , total body potassium , and dual energy x-ray absorptiometry ) , circulating lipids , glucose and insulin concentrations , cardiac 2-dimensional and Doppler echocardiography , and exercise tolerance were assessed before and after the treatment period . Continuous GH therapy had no significant effect on body weight , but it prevented the increase in waist circumference and waist to hip ratio that occurred in the patients without GH substitution ( waist to hip ratio , group A , 0.87+/-0.08 at baseline , 0.85+/-0.09 at 7 yr ; group B , 0.89+/-0.11 at baseline , 0.94+/-0.11 at 7 yr ; P GH-induced decrease in subscapular skinfold thickness was also observed . By bioimpedance analysis , GH therapy caused an increase in total body water and fat-free mass , and a decrease in the percent body fat . Although changes occurred with time in all groups , no significant additional GH therapy effects were observed on glucose tolerance , insulin concentrations , lipid levels , cardiac dimensions , echocardiographic diastolic function , or exercise tolerance . In conclusion , prolonged GH substitution in middle-aged hypopituitary adults causes a sustained improvement in body composition . Other benefits , e.g. on lipid levels and exercise tolerance , were not apparent at 7 yr when comparisons were made with GH-untreated hypopituitary controls . Potentially adverse effects on glucose tolerance and insulinemia did not develop with prolonged GH therapy", "Since the effects of recombinant human growth hormone ( rhGH ) replacement therapy on glucose metabolism are still a matter of debate , the aim of the present study was to evaluate the impact of long-term rhGH treatment on insulin sensitivity . Simple indices of insulin resistance ( IR ) and insulin sensitivity ( IS ) , based on fasting glucose and insulin , such as the homeostasis model assessment of insulin resistance ( HOMA-IR ) and the quantitative insulin check index ( QUICKI ) , were used to estimate the degree of IR and IS in 20 normoglycemic patients ( 11 men and 9 women ; mean age , 44 + /- 14 years ) with severe adult-onset GH deficiency ( GHD ) . Measurements were determined at baseline and after 1 and 5 years of continuous rhGH therapy . Basal values were compared to those obtained in 20 healthy sex- and age-matched controls . Starting rhGH dose ranged from 3 to 8 microg/kg/d in keeping with sex and age , then doses were titrated according to insulin-like growth factor-I ( IGF-I ) levels . At baseline all patients had low IGF-I levels ( 10 + /- 5.4 nmol/L ) , high body mas index ( BMI ; 27.5 + /- 4 kg/m(2 ) ) , and elevated body fat percentage ( BF% ; 31.8 + /- 9.6 ) . Fasting glucose and insulin levels , as well as HOMA-IR and QUICKI , did not differ significantly from those recorded in the control group . After 1 year of rhGH replacement therapy , normalization in IGF-I levels and a significant reduction in BF% were observed ( P Fasting glucose increased from 79 + /- 10 to 87 + /- 13 , and 87 + /- 12 mg/dL ( P Fasting insulin significantly increased after 1 year , without further modifications in the long-term follow-up . HOMA-IR significantly increased from 2.1 + /- 1.7 to 2.5 + /- 1.7 ( P QUICKI from 0.37 + /- 0.05 to 0.34 + /- 0.03 ( P impaired fasting glucose . In conclusion , rhGH therapy determined an increase in fasting glucose and insulin levels , causing in the short-term period a worsening of IS . The sustained reduction in BF% , without further deterioration of IS , suggests that long-term beneficial effects on body composition may overcome the negative influence of GH on glucose metabolism", "BACKGROUND Growth hormone-deficient adults have increased cardiovascular mortality . Growth hormone replacement may affect cardiovascular risk . Inflammation plays an important role in atherosclerosis , and inflammatory markers are predictive of cardiovascular events . OBJECTIVE To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors . DESIGN R and omized , single-blind , placebo-controlled trial . PATIENTS 40 men with adult-onset growth hormone deficiency . INTERVENTION Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level . MEASUREMENTS Anthropometric , hemoglobin A1c , and central fat values were assessed every 6 months . Levels of glucose , insulin , insulin-like growth factor I , and lipids were measured at 1 , 3 , 6 , 12 , and 18 months . C-reactive protein , serum amyloid polypeptide A , inteleukin-6 , and lipoprotein(a ) levels were determined at baseline and 6 and 18 months . RESULTS C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients ( differences between groups , -1.9 + /- 0.6 mg/L [ P = 0.0027 ] and -1.3 + /- 0.5 ng/L [ P = 0.013 ] , respectively ) . Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance ( difference between groups , -2.4 + /- 1.2 mg/L ; P = 0.056 ) . Serum cholesterol levels , low-density lipoprotein cholesterol levels , and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients ( differences between groups , -0.86 + /- 0.17 mmol/L [ -33.2 + /- 6.6 mg/dL ] [ P Lipoprotein(a ) levels increased ( difference between groups , 22.0 + /- 8.0 mg/L ; P = 0.0096 ) . Short-term increases occurred in glucose levels , insulin levels , and insulin-to-glucose ratios ( differences between groups , 0.54 + /- 0.16 mmol/L [ 9.6 + /- 2.8 mg/dL ] [ P = 0.0018 ] , 37.9 + /- 9.6 pmol/L [ P glucose level was maintained over the long term ( difference between groups , 0.56 + /- 0.17 mmol/L [ 10.0 + /- 3.1 mg/dL ] ; P = 0.0026 ) . Hemoglobin A1c values did not change . Truncal fat-to-total fat ratios decreased ( difference between groups , -0.018 + /- 0.007 ; P = 0.0087 ) . CONCLUSIONS Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers , decreases central fat , and increases lipoprotein(a ) and glucose levels without affecting lipid levels", "The Pituitary Society in conjunction with the European Neuroendocrine Association held a consensus workshop to develop guidelines for diagnosis and treatment of the co-morbid complications of acromegaly . Fifty nine pituitary specialists ( endocrinologists , neurosurgeons and cardiologists ) assessed the current published literature on acromegaly complications in light of recent advances in maintaining tight therapeutic control of GH hypersecretion . The impact of elevated GH levels on cardiovascular disease , hypertension , diabetes , sleep apnea , colon polyps , bone disease , reproductive disorders , and neuropsychologic complications were considered . Guidelines are proposed for effective management of these complications in the context of overall acromegaly control . When appropriate , requirements for prospect i ve evidence -based studies and surveillance data base development are enunciated . Effective management of co-morbid acromegaly complications will lead to improved morbidity and mortality in acromegaly", "OBJECTIVE Growth hormone ( GH ) has been suggested to modulate the release of some cytokines including TNF-alpha . To investigate TNF-alpha levels in children with GH deficiency ( GHD ) , to evaluate alteration in TNF-alpha levels during recombinant human GH ( rhGH ) treatment , and to analyze possible correlations between TNF-alpha and GH , IGF-1 and IGFBP-3 . DESIGN Twenty-four children , aged 12.60+/-2.27 years , with isolated GHD and given rhGH therapy , as subcutaneous ingestion of 0.03 - 0.04mg/kg once-daily dose , were evaluated . Eleven had complete and 13 had partial GHD . Thirty-three healthy children were studied as controls . Age and sex distribution , body mass indexes of two groups were similar . In children with GHD , blood sample s were drawn before ( TNF-alpha0 ) , and at 6 ( TNF-alpha6 ) and 12 ( TNF-alpha12 ) months of the treatment with rhGH . TNF-alpha was determined using a human TNF-alpha ELISA assay ( Bio source International ) . RESULTS TNF-alpha0 levels were significantly higher in children with GHD than in controls ( 41.79+/-25.04 and 8.63+/-4.48pg/ml , respectively , p rhGH treatment ( TNF-alpha0=41.79+/-25.04 , TNF-alpha6=13.67+/-9.95 , TNF-alpha12=10.86+/-6.61pg/ml , p TNF-alpha levels and BMI , IGF-1/logIGF1 , IGFBP-3 levels and growth velocity of the patients with GHD . Although no correlation between TNF-alpha and peak GH levels after stimulation was present ; a moderate reverse correlation between TNF-alpha and basal serum concentrations of GH ( r=-0.512 , p=0.046 ) was demonstrated . CONCLUSIONS TNF-alpha levels are significantly higher in children with GHD than the controls , and long-term therapy with rhGH effectively reduces its level . Our data suggest that GH plays an inhibitory role on TNF-alpha release in humans . However , due to inconsistent results up to now , further prospect i ve , controlled and long term studies are needed to eluci date the issue", "OBJECTIVE GH deficiency ( GHD ) in adults is associated with adverse effects on metabolism and increased cardiovascular risk . Pregnancy-associated plasma protein-A ( PAPP-A ) is a protease that promotes IGF-I availability in vascular tissues . PAPP-A levels appear to correlate with carotid intima-media thickness and have been proposed as an early predictor of cardiac events . The aim of our study was to evaluate PAPP-A levels in GHD adults at baseline and after GH replacement and correlate them with changes in body composition , lipid profile , glucose homeostasis , inflammatory markers and in leptin and adiponectin . PATIENTS AND METHODS Fourteen GHD adults were evaluated at baseline and after 1 year of GH therapy . All patients were compared at baseline with 28 age- , sex- and body mass index ( BMI ) -matched control subjects . RESULTS At baseline , GHD adults showed higher PAPP-A levels ( P=0.03 ) and higher leptin ( P=0.04 ) , fibrinogen ( P=0.002 ) and highly sensitive C-reactive protein ( P=0.01 ) values than controls . Therapy with GH reduced PAPP-A ( P=0.03 ) and fibrinogen levels ( P=0.002 ) while increased BMI ( P=0.01 ) and reduced waist-hip ratio ( WHR ; P=0.05 ) were observed . Insulin and homeostasis model assessment of insulin resistance index increased after treatment ( P leptin or adiponectin levels . PAPP-A values correlated positively with BMI and WHR and negatively with adiponectin before and after treatment , with no correlation with glucose homeostasis parameters , lipid profile or leptin . CONCLUSIONS Our study suggests that PAPP-A expression is increased in GHD adults , and that 1 year of GH replacement therapy is able to reduce PAPP-A levels in this population . However , further studies are required to determine whether this decrease correlates with an improvement in atherosclerosis", "CONTEXT Treatment of GH-deficient adolescents in transition to adulthood remains challenging . OBJECTIVE The objective was to assess the safety and efficacy of GH in GH-deficient adolescents in transition . PATIENTS Fifty-eight GH-deficient adolescents ( mean age , 15.8 + /- 1.8 yr ; 33 males ) at near completion of their linear growth participated in the study . INTERVENTION Baseline studies were done while subjects were on GH . Subjects were retested ( insulin-induced hypoglycemia ) 4 wk after GH discontinuation and reclassified as persistently GH-deficient or controls ( n = 18 ) . GH-deficient subjects were r and omized to GH ( n = 25 , approximately 20 microg/kg.d ) or placebo ( n = 15 ) . SETTING The multicenter study was conducted over a 2-yr period . MAIN OUTCOMES Changes in body composition , bone mineral density ( BMD ) , quality of life ( QOL ) , cardiovascular and metabolic markers were measured . RESULTS All groups had normal measures of lipid and carbohydrate metabolism , body composition , BMD , cardiac function , muscle strength , and QOL at baseline and after 2 yr . IGF-I concentrations decreased in all , but less so in the GH-group ( P = 0.013 ) . There was a greater increase in lean body mass ( lesser adiposity ) in the GH group than placebo at 12 months , but not at 24 months . CONCLUSIONS 1 ) GH-deficient patients properly treated in childhood can have normal BMD , body composition , cardiac function , muscle strength , carbohydrate and lipid metabolism , and QOL when reaching adult height ; and 2 ) continuation of GH therapy for 2 yr did not change these measures as compared to placebo-treated or control subjects . GH-deficient adolescents in good metabolic status at the time of epiphyseal fusion may safely discontinue GH for at least 2 yr . Follow-up is needed to determine whether GH therapy is eventually warranted in subjects treated with GH during childhood", "Hypopituitary patients have an increased risk of vascular mortality that may relate to growth hormone deficiency ( GHD ) . We investigated the effects of 6 months of GH therapy on large‐ and small‐artery function and high‐sensitivity C‐reactive protein ( hsCRP ) in a cohort of GH‐deficient patients . Sixteen hypopituitary patients were r and omized to 6 months of GH therapy or no treatment , then vice versa . hsCRP , 24‐h blood pressure ( BP ) and pulse wave velocity ( PWV ) were measured and resistance arteries were used to construct concentration – response curves to endothelium‐dependent and ‐independent agents . GH therapy increased IGF‐1 from 60 ± 7·2 to 167 ± 16·2 µg/l [ confidence interval ( CI ) 94·9 , 138·8 , P declined after 6 months of GH from 3·8 ± 0·88 to 2·0 ± 0·49 mg/l ( CI 0·73 , 3·57 , P = 0·006 ) . Mean arterial BP fell from 91·7 ± 1·5 to 89·3 ± 1·2 mmHg ( CI 0·81 , 4·07 , P = 0·005 ) , as did PWV ( 8·1 ± 0·4 to 6.7 ± 0·5 m/s ) . The decline in PWV correlated with the decline in hsCRP ( r = 0·68 , P = 0·01 ) . Resistance artery function was unchanged after GH therapy . GH replacement may lead to differentially altered production of vasorelaxant agents from the endothelium of large and small arteries . Reduction in vascular inflammation may be associated with reduced vascular risk", "Patients with growth hormone deficiency ( GHD ) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events . An increase in asymmetric dimethylarginine ( ADMA ) levels previously found in GHD patients could promote premature atherosclerosis . The aim of this study was to determine whether 6-month growth hormone ( GH ) replacement therapy was able to decrease ADMA levels and ameliorate endothelial dysfunction . Thirty-one GHD patients were studied before and after 6 months of GH ( 4 microg/[kg d ] , daily ) replacement therapy . Reduced pretreatment levels of serum insulin-like growth factor ( IGF ) 1 were normalized during GH treatment ( 88.2 + /- 62.5 to 191.7 + /- 80.3 ng/mL , P plasma cyclic guanosine monophosphate levels significantly increased ( 2.14 + /- 0.52 to 3.54 + /- 1.2 ng/mL , P serum ADMA levels were significantly decreased ( 0.65 + /- 0.1 vs 0.59 + /- 0.11 mumol/L , P arganine ( Arg ) to ADMA ratio was significantly higher ( 155 + /- 53 vs 193 + /- 61 , P plasma nitric oxide end products ( nitrite and nitrate ) levels after GH treatment ( 21.9 + /- 14.9 vs 24.1 + /- 19.0 mumol/L , not significant ) . Basal forearm blood flow remained unchanged , whereas reactive hyperemia increased from 7.30 + /- 5.31 mL/100 mL forearm per minute before GH therapy to 13.18 + /- 7.30 mL/100 mL forearm per minute after 6 months of therapy ( P IGF-1 and cyclic guanosine monophosphate ( r = 0.73 , P IGF-1 and reactive hyperemia ( r = 0.63 , P IGF-1 and Arg/ADMA ratio ( r = 0.44 , P IGF-1 and ADMA levels ( r = -0.41 , P fat-free mass , plasma glucose , and hemoglobin A(1c ) levels significantly increased , even if they were still in the reference range , suggesting moderate alteration of glucose metabolism . In conclusion , in GHD patients , GH replacement contributes to decreased , to some extent , cardiovascular risk , reducing ADMA levels and improving Arg/ADMA ratio and endothelial dysfunction", "Adiponectin is found to associate with diabetes in studies apart from cohort studies . This prospect i ve cohort study is to evaluate the predictive role of adiponectin in diabetes among participants with impaired fasting glucose ( IFG ) . A total of 42,845 participants who visited 7 health examination centers located in Seoul and Kyunggi province , South Korea , during 2004–2008 were first included . Of the 42,845 participants , 5,085 participants had IFG . IFG was categorized as stage 1 ( fasting glucose 100–109 mg/dL ) or stage 2 ( 110–125 mg/dL ) . The incidence rates of diabetes were followed up to December , 2011 . Hazard ratios ( HRs ) and 95 % confidence intervals ( CI ) were performed by Cox proportional hazard model . Of the 5,085 participants , 652 participants developed diabetes during a mean follow-up of 4.4 years . Low adiponectin was associated with diabetes among men with stage 2 IFG ( HR , 1.78 ; 95 % CI , 1.33–2.38 ) while it was associated with diabetes among women with stage 1 IFG ( HR , 2.64 ; 95 % CI , 1.38–5.03 ) and stage 2 IFG ( HR , 2.17 ; 95 % CI , 1.07–4.42 ) . When combined men and women , the association between adiponectin and diabetes was statistically significant in stage 2 IFG with an increase of about 82 % ( HR , 1.82 ; 95 % CI , 1.40–2.39 ) after adjusting for age , sex , body mass index , waist circumference , and fasting serum glucose . There was an interaction by sex and stage 1 IFG in the association between adiponectin and risk of diabetes ( P with diabetes among participants with IFG . This association was apparent in stage 2 IFG . Adiponectin may be used as a predictor of diabetes in patients having IFG", "Objective : Adult GH deficiency ( GHD ) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality . Oxidative stress appears to play an important role in early atherogenesis . Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium . Its concentrations are increased in GHD , but the association between this abnormality and oxidative stress is still unclear , due to the discordant results yielded by the few available studies . Design and methods : In 13 GHD patients , plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH ( rhGH ) and compared with those of 13 age- and sex-matched controls . In the same subjects , the so-called “ lag-time ” , an index of anti-oxidant activity and thus of plasma oxidative balance , was also measured using a fluorescence kinetics method . Results : Before treatment , peroxide levels were significantly higher in patients than in controls ( 374.0±31.52 vs 268.0±8.51 U.C. , p the lag-time was significantly lower ( 113.0±10.70 vs 168.0±7.80 min , p ) . RhGH administration to patients result ed both in a significant decrease in lipid peroxide levels ( from 374.0±31.52 to 336.0±33.17 U.C. , p prolongation of lag-time ( from 113.0±10.70 to 144.0±15.00 min , p controls . Lagtime and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients . After replacement therapy , however , lag-time was positively ( r2= 0.62 , p and peroxide levels negatively ( r2=0.41 , p GHD patients , is corrected by short-term GH administration at a dose able to increase , although not to fully normalize , IGF-I levels", "objectives Untreated growth hormone deficiency ( GHD ) is implicated in the increased cardiovascular risk associated with adult hypopituitarism . Oxidative stress , predisposing to lipid peroxidation , may be an important mediator of endothelial dysfunction , a pro‐atherogenic state associated with adult GHD", "OBJECTIVE Increased cardiovascular mortality/morbidity observed in patients with hypopituitarism is ascribed to growth hormone deficiency ( GHD ) because of its unfavorable cardiovascular risk profile . Abnormalities in the coagulation system may also contribute to increased cardiovascular morbidity/mortality . To get a better insight into the role of hemostasis in GHD we assessed several hemostatic markers at baseline and after 6 months of GH replacement therapy ( GHRT ) . DESIGN - PATIENTS : Nineteen patients with adult onset GHD were enrolled ( twelve patients into the treatment and seven patients into the placebo group ) into the study . Platelet count , collagen/epinephrine closure time , collagen/ADP closure time , fibrinogen , prothrombin time ( PT ) , activated partial thromboplastin time ( aPTT ) , antithrombin III ( AT III ) , protein C activity , protein S activity , lupus anticoagulant , antiphospholipid antibody immunoglobulin M , and antiphospholipid antibody immunoglobulin G were measured at baseline and 6 months after treatment . RESULTS The investigated parameters in the groups were similar at baseline except for low protein S ( PS ) activity . Protein S deficiency was observed in three of the patients in the GH treatment group at baseline , however the PS activity values normalized following GHRT . AT III and protein C activities decreased when compared to baseline values in the treatment group but not in the placebo group . CONCLUSIONS We observed protein S deficiency more frequent than seen in the general population and normalization of protein S activity and decreases , in other natural anticoagulants following GHRT . Further studies are required to underst and the impact of these changes in cardiovascular morbidity and mortality in this patient population", "It is now a consensus to resume GH treatment in adolescents with severe GH deficiency ( GHD ) at retesting to prevent the occurrence of adult GHD syndrome . However , we do not have any data on the follow-up of adolescents with nonsevere GHD at completion of treatment . This report presents preliminary data from a 1-yr prospect i ve study that includes the first 91 patients retested . Anthropometric data , IGF-I and IGF binding protein-3 levels , glycemia and insulinemia , lipid profile , and body composition using dual x-ray absorptiometry and abdominal computed tomography scan were recorded at completion of GH treatment and 1 yr later . Body composition was significantly different at both evaluations , with increased total body fat and decreased lean body mass in the partial GHD group vs. the normal group . Moreover , these alterations worsened after 1 yr without GH in the partial GHD group , whereas there were no modifications in the normal group . We did not find any metabolic alterations such as elevated triglyceride , total cholesterol , or insulin levels . Adolescents with reconfirmed partial GHD exhibit alterations in body composition after 1 yr without GH , whereas those retested normal do not . These changes are similar to those described in severe GHD , although less marked , and justify a precise follow-up", "CONTEXT Patients with hypopituitarism have an increased st and ardized mortality rate . The basis for this has not been fully clarified . OBJECTIVE To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up . DESIGN AND METHODS All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospect ively monitored in KIMS ( Pfizer International Metabolic Data base ) 1995 - 2009 were compared to general population data in the Swedish National Cause of Death Registry . In addition , events reported in KIMS , medical records , and postmortem reports were review ed . MAIN OUTCOME MEASURES St and ardized mortality ratios ( SMR ) were calculated , with stratification for gender , attained age , and calendar year during follow-up . RESULTS An excess mortality was found , 120 deaths vs 84.3 expected , SMR 1.42 ( 95 % confidence interval : 1.18 - 1.70 ) . Infections , brain cancer , and sudden death were associated with significantly increased SMRs ( 6.32 , 9.40 , and 4.10 , respectively ) . Fifteen patients , all ACTH-deficient , died from infections . Eight of these patients were considered to be in a state of adrenal crisis in connection with death ( medical reports and post-mortem examinations ) . Another 8 patients died from de novo malignant brain tumors , 6 of which had had a benign pituitary lesion at baseline . Six of these 8 subjects had received prior radiation therapy . CONCLUSION Two important causes of excess mortality were identified : first , adrenal crisis in response to acute stress and intercurrent illness ; second , increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy . Both of these causes may be in part preventable by changes in the management of pituitary disease", "Previous studies have demonstrated beneficial effects of GH replacement , in adults with GH deficiency ( GHD ) , on body composition , physical fitness , and quality of life . These studies , however , concern patients with adult-onset GHD or childhood-onset ( CO ) patients enrolled several years after withdrawal of initial therapy . So far , the effects of continuation of GH-administration in patients with CO-GHD have not been examined . We studied a group of nineteen young adults ( 13 males + 6 females ; 16 - 26 yr old ; mean age , 20.2 + /- 0.65 yr ) with CO-GHD , in a r and omized , parallel , double-blind , placebo-controlled trial for 1 yr , followed by an open phase with GH for 1 yr . All patients received GH therapy at the start of study , and trial medication ( GH/placebo ) was given in a similar dose . Patients r and omized to continued GH treatment exhibited no significant changes in any parameters tested , but intra- and interindividual variations in insulin-like growth factor (IGF)-I levels could suggest compliance problems . Discontinuation of GH for 1 yr result ed in a decrease in serum IGF-I , from 422.0 + /- 56.8 to 147.8 + /- 33.4 microg/L , in the placebo group ( P = 0.003 ) . After discontinuation of GH for 1 yr , an increase in total body fat ( TBF , kg ) , measured by dual-energy x-ray absorptiometry scan , was seen [ placebo : 22.7 + /- 2.7 to 26.5 + /- 2.5 ( P = 0.01 ) ; GH : 16.2 + /- 2.1 to 17.2 + /- 2.1 ( not significant ) ] . Resumption of GH after placebo was followed by increments in serum IGF-I ( microg/L ) [ from 147.8 + /- 33.4 to 452 + /- 76 ( P = 0.001 ) ] and IGF-binding protein 3 , as well as in fasting glucose ( mmol/L ) [ 4.9 + /- 0.2 vs. 5.3 + /- 0.2 ( P = 0.03 ) ] . After resumption of GH lean body mass ( kg ) increased [ 52.4 + /- 4.9 vs. 60.7 + /- 5.6 ( P = 0.006 ) ] . Likewise , resumption of GH therapy increased thigh muscle volume and thigh muscle/fat ratio , as assessed by computed tomography [ muscle volume ( cm2/10 mm ) : 118.2 + /- 11.7 vs. 130.0 + /- 10.9 ( P = 0.002 ) ; muscle/fat ratio : 1.33 + /- 0.24 vs. 1.69 + /- 0.36 ( P = 0.02 ) ] . In conclusion , discontinuation of GH treatment in GHD patients , during the transition from childhood to adulthood , induces significant and potentially unfavorable changes in IGF-I and body composition , both of which are reversed after resumption of GH treatment . By contrast , continuation of GH therapy results in unaltered IGF-I and body composition . We recommend continuation of GH therapy in these patients , to be undertaken in collaboration between pediatricians and adult endocrinologists", "The effects of GH replacement therapy on energy metabolism are still uncertain , and long-term benefits of increased muscle mass are thought to outweigh short-term negative metabolic effects . This study was design ed to address this issue by examining both short-term ( 1 wk ) and long-term ( 6 months ) effects of a low-dose ( 9.6 micro g/kg body weight.d ) GH replacement therapy or placebo on whole-body glucose and lipid metabolism ( oral glucose tolerance test and euglycemic hyperinsulinemic clamp combined with indirect calorimetry and infusion of 3-[(3)H]glucose ) and on muscle composition and muscle enzymes/metabolites , as determined from biopsies obtained at the end of the clamp in 19 GH-deficient adult subjects . GH therapy result ed in impaired insulin-stimulated glucose uptake at 1 wk ( -52 % ; P = 0.008 ) and 6 months ( -39 % ; P = 0.008 ) , which correlated with deterioration of glucose tolerance ( r = -0.481 ; P = 0.003 ) . The decrease in glucose uptake was associated with an increase in lipid oxidation at 1 wk ( 60 % ; P = 0.008 ) and 6 months ( 60 % ; P = 0.008 ) and a concomitant decrease in glucose oxidation . The deterioration of glucose metabolism during GH therapy also correlated with the enhanced rate of lipid oxidation ( r = -0.508 ; P = 0.0002 ) . In addition , there was a shift toward more glycolytic type II fibers during GH therapy . In conclusion , replacement therapy with a low-dose GH in GH-deficient adult subjects is associated with a sustained deterioration of glucose metabolism as a consequence of the lipolytic effect of GH , result ing in enhanced oxidation of lipid substrates . Also , a shift toward more insulin-resistant type II X fibers is seen in muscle . Glucose metabolism should be carefully monitored during long-term GH replacement therapy", "A retrospective comparison was performed between 1411 hypopituitary adults without GH replacement [ mean age , 56.9 ( sd 18.6 ) yr ] and the normal population in terms of fatal and nonfatal morbidity . A similar prospect i ve comparison was then made in 289 hypopituitary patients on long-term GH replacement [ mean age , 47.6 ( sd 14.8 ) yr ; mean duration of GH treatment , 60 months ] . In the 1411 hypopituitary patients without GH replacement , overall mortality ( P rates of myocardial infa rct ions ( P cerebrovascular events ( P malignancies ( P Colorectal cancer was the most common malignancy in this cohort ( P 289 hypopituitary patients on GH replacement , overall mortality and the rate of malignancies were similar to the normal population . In the hypopituitary adults on GH therapy , the rate of myocardial infa rct ions was lower than that in the background population ( P rate of cerebrovascular events . In conclusion , overall mortality and the rate of myocardial infa rct ions were increased in hypopituitary patients without GH replacement . An increased rate of malignancies was observed in the hypopituitary adults without GH therapy , with a predominance of colorectal cancer . GH replacement appeared to provide protection from myocardial infa rct ions . The rate of cerebrovascular events tended to be increased also in hypopituitary adults on GH therapy", "OBJECTIVE The ob gene product , leptin , is considered to be a marker of adipose tissue mass and a possible homeostatic regulator of body mass . Our objective was to examine the effect of GH replacement on adipose tissue stores and leptin in adult hypopituitarism", "OBJECTIVE Patients with growth hormone deficiency ( GHD ) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein ( HDL ) cholesterol concentrations , two lipid abnormalities usually accompanied by increased small dense LDL in the ' atherogenic lipoprotein phenotype ' ( ALP ) . In the present study , we directly investigated ( 1 ) whether hypopituitary patients with GHD have increased small dense LDL ; ( 2 ) whether growth hormone replacement therapy ( GHRT ) beneficially impact on such particles ; ( 3 ) the prevalence of ALP in GHD and GHRT patients . DESIGN AND METHODS In 14 hypopituitary patients with GHD ( 44 + /- 13 years , body mass index ( BMI ) 27 + /- 3 ) before and after 4 months of GHRT , and in 11 healthy age- and BMI -matched controls we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis . RESULTS Compared with controls , GHD showed increased triglycerides ( P = 0.0024 ) , similar total and LDL cholesterol levels and a tendency towards reduced HDL cholesterol concentrations ( P = 0.0894 ) . GHRT reduced total and LDL cholesterol levels ( P = 0.0303 and 0.0120 respectively ) , but no effect was found on triglycerides and HDL cholesterol levels . LDL size was unchanged in GHD versus controls ( 269 + /- 9 vs 274 + /- 6 A , P = ns ) , but LDL subclass analysis revealed a shift towards more dense particles ( P = 0.0046 ) . GHRT had no significant impact on LDL size and subclasses . The prevalence of ALP was 14 % in GHD and 7 % in GHRT . CONCLUSIONS In GHD patients , individual features of ALP ( including increased small dense LDL ) may be common , but complete ALP is relatively uncommon . Short-term replacement therapy seems to be ineffective on such lipid alterations , but the effect of a longer GHRT remains to be assessed", "CONTEXT Although it has been hypothesized that hypertension is in part an inflammatory disorder , clinical data linking inflammation with incident hypertension are scarce . OBJECTIVE To examine whether C-reactive protein levels , a marker of systemic inflammation , are associated with incident hypertension . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood sample s with initially normal levels of blood pressure ( BP ) ( systolic BP history of hypertension or antihypertensive medications ) and then followed up for a median of 7.8 years for the development of incident hypertension . Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected . MAIN OUTCOME MEASURE Incident hypertension , defined as either a new physician diagnosis , the initiation of antihypertensive treatment , or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg . RESULTS During follow-up , 5365 women developed incident hypertension . In crude models , the relative risks ( RRs ) and 95 % confidence intervals ( CIs ) of developing hypertension from the lowest ( referent ) to the highest levels of baseline C-reactive protein were 1.00 , 1.25 ( 95 % CI , 1.14 - 1.40 ) , 1.51 ( 95 % CI , 1.35 - 1.68 ) , 1.90 ( 95 % CI , 1.72 - 2.11 ) , and 2.50 ( 95 % CI , 2.27 - 2.75 ) ( linear trend P C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated , including those with very low levels of baseline BP , as well as those with no traditional coronary risk factors . Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP . CONCLUSION C-reactive protein levels are associated with future development of hypertension , which suggests that hypertension is in part an inflammatory disorder ", "BACKGROUND Severe GH deficiency ( GHD ) is associated with , increased cardiovascular risk and intima-media thickness ( IMT ) at major arteries . OBJECTIVE The objective of the study was to investigate the 5-yr effects of GH replacement on common carotid IMT and insulin resistance syndrome ( IRS ) ( at least two of the following : triglycerides levels > or = 1.7 mmol/liter , high-density lipoprotein-cholesterol levels Patients included 35 men with severe GHD and 35 age-matched healthy men as controls . INTERVENTION All patients received st and ard replacement therapy ; GH replacement was added in 22 patients ( group A ) and refused by 13 others ( group B ) . MEASUREMENTS Five-year changes in IMT and IRS prevalence were measured . RESULTS At baseline , IMT was higher in the patients with ( P . At study end , use of lipid-lowering drugs ( 92.3 , vs. 13.6 and 34.3 % , P glucose-lowering drugs ( 69.2 vs. 31.4 and 22.7 % ; P = 0.016 ) , and antihypertensive drugs ( 61.5 vs. 20.0 and 4.5 % ; P IGF-I levels normalized in all group A patients and remained lower than -1 sd score in 77 % of group B patients . IMT significantly decreased only in group A and significantly increased in controls and nonsignificantly in group B patients . IRS prevalence significantly reduced only in group A patients . CONCLUSIONS Severely hypopituitary GHD men have more frequently increased IMT at common carotid arteries and IRS than controls . After 5 years , only in GH replaced patients , IMT and prevalence of IRS decreased", "The gene product from the ob gene , leptin , has recently been characterized in humans . The circulating level of leptin is related to body mass index ( BMI ) and more closely to estimates of total body fat , whereas visceral fat has been reported to be of minor importance . However , it is unknown if leptin is directly regulated by hormones that influence substrate metabolism and body composition . We studied leptin in adult growth hormone (GH)-deficient ( GHD ) patients substituted with GH treatment for 12 months in a parallel double-blind , placebo-controlled study . Twenty-seven GHD adults aged 44.9 + /- 1.9 years underwent anthropometric measurements for determination of regional and total body fat ( BMI , waist to hip ratio [ WHR ] , computed tomographic [ CT ] scan , dual-energy x-ray absorptiometry [ DEXA ] scan , and bioimpedance analysis [ BIA ] ) before and after 12 months of placebo-controlled GH substitution ( 2 IU/m2 ) in a parallel design . The same measurements were performed in 42 healthy adults aged 39.1 + /- 1.7 years . The logarithm of serum leptin levels correlated positively with abdominal subcutaneous fat and total body fat ( BIA and DEXA ) in untreated GHD patients and healthy subjects . Fasting insulin did not correlate with leptin levels in either of the groups . After 12 months of GH administration , the body composition of GHD patients was significantly changed with respect to a marked decrease in body fat . The relations of leptin to the estimates of body fat were maintained , and leptin was furthermore related to BMI and fasting insulin . In multiple linear regression analyses , additional estimates of visceral adiposity ( intraabdominal fat and maximal anterior-posterior diameter determined by CT scan ) were significant determinants of leptin in the healthy subjects . The increase in fasting insulin levels during GH substitution correlated negatively with the reduction in leptin levels ( r = -.823 , P = .003 ) . At baseline , leptin levels were increased in the patients compared with controls in both sexes ( women , 21.8 + /- 3.3 v 11.3 + /- 1.4 ng/mL , P = .002 ; men , 8.1 + /- 1.2 v 4.7 + /- 0.7 ng/mL , P = .008 ) . Leptin levels were similar in GHD patients treated for 12 months compared with healthy controls for both women and men ( women , 15.9 + /- 2.3 and 11.3 + /- 1.4 ng/mL , P = .163 ; men , 7.1 + /- 2.8 and 4.7 + /- 0.7 ng/mL , P = .759 ) . In healthy adults and in GHD patients , leptin levels were significantly higher in women than in men ( 11.3 + /- 1.4 v 4.7 + /- 0.7 ng/mL , P leptin levels in several models of multiple linear regression analysis also including age , estradiol levels , insulin , and estimates of body fat . We conclude that leptin is increased but not differently regulated in GHD patients compared with normal subjects , and that leptin levels are closely related to estimates of body fat . This relationship is maintained during a decrease in body fat due to GH substitution", "OBJECTIVE The long‐term cardiovascular effects of GH administration in adults are of major clinical importance , given the increasing use of such treatment . We have evaluated long‐term cardiovascular effects of recombinant human GH ( rhGH ) substitution in GH deficient men", "OBJECTIVE We have studied the effects on body composition and metabolism of a fixed low dose of growth hormone ( GH ) , 0.6 IU ( 0.2 mg)/day , administered for 12 months to GH-deficient ( GHD ) adults . DESIGN AND METHODS Prospect i ve open-label study , using 18 GHD patients ( 11 women , 7 men ; aged 21 - 58 years ) . All investigations were performed at baseline and after 12 months . Body composition was determined by dual energy X-ray absorptiometry . RESULTS Total body fat decreased ( -1.74+/-2.87 % ) and lean body mass ( LBM ) increased ( 1.27+/-2.08 kg ) after therapy ( P in truncal fat did not reach statistical significance , but a decrease varying from 0.72 to 2.78 kg ( 1 to 8.7 % ) was observed in 13 ( 72 % ) patients . Bone mineral density ( BMD ) increased at lumbar spine , total femur and femoral neck ( P Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy ( P Insulin levels increased and the insulin resistance index worsened at 12 months ( P Median IGF-I s.d . score was -4.30 ( range , -11.03 to -0.11 ) at baseline and -1.73 ( range , -9.80 to 2.26 ) at 12 months . Normal age-adjusted IGF-I levels were obtained with therapy in 5 of 11 patients who had low IGF-I levels at baseline . Changes in IGF-I levels were not correlated with any biological end point , except changes in LBM ( r = 0.53 , P = 0.02 ) . Side effects were mild and disappeared spontaneously . CONCLUSIONS One-year of a fixed low-dose GH regimen in GHD adults result ed in a significant reduction in body fat , total cholesterol and LDL-cholesterol , and a significant increase in LBM and BMD at lumbar spine and femur , regardless of normalization of IGF-I levels . This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index", "GH deficiency ( GHD ) is associated with increased prevalence of atherosclerosis and cardiovascular morbidity . Because monocytes play a crucial role in the development of atherosclerosis , we investigated in the present study the effect of GH deficiency and subsequent GH replacement on monocytic function in hypopituitary subjects . Twelve patients were r and omized to receive GH replacement therapy ( either 3 or 6 microg/kg x day , s.c . ) for 3 months . Plasma levels and monocyte production of cytokines and monocyte adhesion to endothelium were determined in controls and patients with GHD before and after GH treatment . Before GH therapy , patients with GHD had increased basal plasma tumor necrosis factor-alpha ( TNF alpha ; 220 % over control values ; P = 0.004 ) and interleukin-6 ( IL-6 ; 340 % over control values ; P 0.0009 ) levels . Basal monocyte production of both cytokines was also significantly higher in patients with GHD [ 484 % over control values for TNF alpha ( P = 0.0007 ) ; 1479 % over control values for IL-6 ( P = 0.035 ) ] . GH treatment for 3 months led to a reduction in plasma TNF alpha ( 135 % over control values ; P = 0.03 , pre- vs. post-GH therapy ) , monocyte TNF alpha production ( 204 % over control values ; P = 0.01 ) , plasma IL-6 ( 219 % over control values ; P = 0.07 ) , and monocyte IL-6 production ( 448 % over control values ; P = 0.01 ) . Plasma TNF alpha levels positively correlated with monocyte TNF alpha production in patients with GHD both before and after GH therapy ( P = 0.003 and P = 0.049 , respectively ) . A positive correlation ( P = 0.0003 ) was also observed between monocyte TNF alpha production and monocyte IL-6 production . There were no correlations between these plasma cytokine levels or monocyte cytokine production and parameters of body composition , lipid profile , or IGF-I and IGF-binding protein-3 levels . Before GH treatment , adhesiveness of monocytes to cultured aortic endothelial cells was also enhanced . This alteration was not reversed by GH administration . In conclusion , our results demonstrate that markers of monocyte activation are increased in patients with GHD and that GH replacement partly reduces these abnormalities . Reduction of cellular activation of monocytes by GH therapy could potentially contribute to reduce the risk of cardiovascular events in patients with GHD", "Lean body mass ( LBM ) , fat mass ( FM ) , and total bone mineral content are significantly reduced in adult GHD subjects who had received pediatric GH . To test the hypothesis that continued GH therapy after final height is necessary to attain adult body composition , we performed a prospect i ve , multinational , r and omized , controlled , 2-yr study in patients who completed pediatric GH treatment at final height . Patients were r and omized to GH at 25.0 microg/kg x d ( pediatric dose ; n = 58 ) or 12.5 microg/kg x d ( adult dose ; n = 59 ) or no GH treatment ( control ; n = 32 ) . LBM and FM were measured by dual energy x-ray absorptiometry and were central ly evaluated . IGF-I , IGF-binding protein-3 , and lipid concentrations were also measured central ly . During the 2 yr , GH-treated patients gained a significant amount of LBM compared with controls ( P decrease in FM was significantly ( P = 0.029 ) influenced by treatment , but with no dose effect ( adult dose , -7.1 + /- 22.8 % ; pediatric dose , -6.0 + /- 26.6 % ; P = 0.950 ) . When the GH treatment effect was analyzed by gender , males gained 15.6 + /- 9.8 % and 14.3 + /- 11.7 % LBM ( P = 0.711 ) and lost 12.4 + /- 22.2 % and 11.0 + /- 27.1 % FM ( P = 0.921 ) with the low and high doses , respectively . Females gained 8.3 + /- 7.3 % and 12.5 + /- 12.8 % LBM with the two doses ( P = 0.630 ) , but increased their FM by 3.5 + /- 16.2 % with the lower dose and lost only 1.2 + /- 23.2 % FM with the higher dose ( P = 0.325 ) . A similar pattern was seen in IGF-I sd score ; the 2-yr GH dose response was significantly higher with the pediatric than with the adult dose in females ( P = 0.008 ) , but not males ( P = 0.790 ) . The divergent pattern of change in LBM and FM in males and females is consistent with normal developmental sexual dimorphism and indicates that GH-dependent progress to target body composition continues after the age at which GH treatment is usually terminated . Dose requirements may have to be adjusted by gender , with females requiring a higher dose than males" ]

[ "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", "The bone mineral content ( B.M.C. ) in both forearms ( related to total body calcium ) was measured by photon absorptiometry for a controlled therapeutic trial in a representative sample of epileptic out patients , comprising 226 patients treated with one or two major anticonvulsant drugs ( phenytoin , phenobarbitone , primidone ) . Initially the mean B.M.C. value for all epileptic patients was 87 % of normal . During treatment with 2,000 international units of vitamin D2 daily for three months an average B.M.C. increase of 4 % was found , whereas the B.M.C. values remained unchanged in the placebo group and in the control groups . The incidence of hypocalcaemia and raised serum alkaline phosphatase was 12 % and 43 % respectively . The biochemical indices of osteomalacia were related to B.M.C. These results indicate that epileptic patients should be closely supervised for the occurrence of anticonvulsant osteomalacia , and , possibly , receive prophylactic treatment with vitamin", "BACKGROUND Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture", "BACKGROUND The objective of the study was to evaluate bone mass status ( as measured by bone ultrasound ) in patients on anticonvulsant therapy , and the influence that Vitamin D administration exerts over it . MATERIAL S AND METHODS We measured and compared the basal serum levels of 25(OH)D3 , parathyroid hormone ( PTH ) , and phalangeal bone ultrasound ( Ad-SOS ) , in 30 adult patients who were taking anticonvulsant drugs , with a control group of similar age and sex . We then gave the patients a large oral dose of 3 mg ( 120.000 UI ) of 25(OH)D3 , and repeated the measurements after one month . RESULTS Basal 25(OH)D3 and Ad-SOS values were significantly lower , and PTH values significantly higher ( P Ad-SOS values for the patients were independent of the treatment , but directly related to basal 25(OH)D3 levels ( r = 0.45 , P PTH and 25(OH)D3 ( r = -0.64 , P PTH y Ad-SOS ( r = -0.20 , p NS ) . After ingestion of the large dose of the vitamin D , the patient group registered a significant ( P 25(OH)D3 levels , their Ad-SOS values increased ( P PTH decreased significantly ( P vitamin D intake in patients being treated with anticonvulsants , independently of the treatment , age , sex , and activity status , in order to prevent osteomalacia", "PURPOSE To evaluate whether use of a bisphosphonate ( risedronate ) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs ( AEDs ) long term can prevent the loss of bone mass ( BMD , bone mineral density ) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures . METHODS Antiepileptic drug and osteoporosis prevention trial ( ADOPT ) was design ed as a prospect i ve 2-year double-blind , r and omized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin , phenobarbital , sodium valproate , or carbamazepine for a minimum of 2 years . All enrolled participants received calcium and vitamin D supplementation , and were r and omized to risedronate or matching placebo . Total body , bilateral proximal femora , and anteroposterior ( AP ) lumbar spine BMDs in addition to morphometric lateral vertebral assessment s ( LVAs ) were evaluated by a dual energy x-ray absorptiometry ( DXA ) instrument . Comparisons of BMDs were made between baseline , 1 year , and after 2 years of enrollment in the study . The incidence of new vertebral and nonvertebral fractures was secondary end point . KEY FINDINGS Of the 80 patients initially enrolled in the study , 53 patients completed the study . Baseline characteristics of the two groups were similar . At the end of the study , in the placebo plus calcium and vitamin D group , we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69 % ( 18/26 ) of the participants . In the risedronate plus calcium and vitamin D group , we observed significant improvement of BMDs in 70 % ( 19/27 ) of the participants . At the end of the study , the risedronate group experienced a significant increase of BMD at the lumbar spine L1 - 4 ( 1.267 - 1.332 g/cm(2 ) ) , which was significantly larger than that seen in the placebo group ) ( 1.229 g/cm(2 ) vs. 1.245 g/cm(2 ) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora . Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group . SIGNIFICANCE Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69 % of male veterans with epilepsy who were taking AEDs . In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group , which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort", "BACKGROUND Long-term therapy with antiepileptic drugs ( AED ) may be associated with increased total serum alkaline phosphatase ( ALP ) levels and reduced serum calcium , inorganic phosphorous , and vitamin D levels . These adverse biochemical alterations have an adverse effect on bone health . OBJECTIVE To determine ( a ) onset of derangements in serum total ALP and its isoenzymes ( liver , bone ) , calcium and 25-hydroxy vitamin D ( 25-OHD ) concentrations after initiation of treatment with phenytoin or valproic acid monotherapy and ( b ) the effect of simultaneous supplementation with calcium and 25-OHD at recommended daily allowance ( RDA ) dosage , on these biochemical parameters . MATERIAL S AND METHODS Study was a prospect i ve , case-controlled study in adults . Serum biochemical parameters were estimated at baseline , 30 , 60 , and 90 days of starting AED treatment in the study subjects : Groups -- A ( only calcium supplementation ) and Group B ( both calcium and 25-OHD supplementation ) . STATISTICAL ANALYSIS Mean+/-SD , and students ' paired t test ( between groups A and B ) unpaired students ' t test ( drug-wise ) . RESULTS At 60 days of AED therapy Group A showed a significant increase in serum total ALP ( 78.83+/-11.04 to 101.75 + /- 9.56 IU/l ) ( P ALP-liver isoenzyme , ( 41.97+/- 10.81 to 68.83 + /-7.81 IU/L ) ( P significant decrease in calcium ( 9.30 + /- 0.36 to 8.80 + /- 0.38 mg% ) ( P ALP-bone isoenyzme ( 36.84 + /- 5.01 to 32.92 + /- 6.46 IU/L ) ( P decrease in 25-OHD ( 25.19 + /- 5.98 to 19.76 + /- 5.35 ng/ml ) ( P serum total ALP ( 81.92 + /- 19.63 to 54.77 . + /- 11.53 IU/L ) ( P ALP-liver isoenzyme ( 48.01 . + /- 13.53 to 28.12 . + /- 5.88 IU/L ) ( P significant increase in calcium ( ( 9.24 + /- 0.31 to 9.93 + /- 0.26 mg% ) ( P ALP-bone isoenzyme levels ( 33.93 + /- 12.2 to 26.25 + /- 8.23 IU/L ) . In Group B , 25-OHD levels showed a significant increase at 90 days ( 24.36 + /- 3.42 to 31.53 + /- 327 ng/ml ) ( P calcium metabolism involving the bone are seen by 60 days after starting AED monotherapy , indicating predisposition to development of osteomalacia in these patients . This is preventable by simultaneous oral supplementation with calcium and 25-OHD" ]

[ "Overweight and obesity affects more than 66 % of the adult population and is associated with a variety of chronic diseases . Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies . Guidelines of the National Heart , Lung , and Blood Institute ( NHLBI ) encourage a 10 % reduction in weight , although considerable literature indicates reduction in health risk with 3 % to 5 % reduction in weight . Physical activity ( PA ) is recommended as a component of weight management for prevention of weight gain , for weight loss , and for prevention of weight regain after weight loss . In 2001 , the American College of Sports Medicine ( ACSM ) published a Position St and that recommended a minimum of 150 min wk(-1 ) of moderate-intensity PA for overweight and obese adults to improve health ; however , 200 - 300 min wk(-1 ) was recommended for long-term weight loss . More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss . To this end , we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain , for weight loss , and prevention of weight regain . Evidence supports moderate-intensity PA between 150 and 250 min wk(-1 ) to be effective to prevent weight gain . Moderate-intensity PA between 150 and 250 min wk(-1 ) will provide only modest weight loss . Greater amounts of PA ( > 250 min wk(-1 ) ) have been associated with clinical ly significant weight loss . Moderate-intensity PA between 150 and 250 min wk(-1 ) will improve weight loss in studies that use moderate diet restriction but not severe diet restriction . Cross-sectional and prospect i ve studies indicate that after weight loss , weight maintenance is improved with PA > 250 min wk(-1 ) . However , no evidence from well- design ed r and omized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss . Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk . Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk . There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain", "BACKGROUND The proportion of overweight adolescents has increased , but the behavioral risk factors for overweight youth are not well understood . OBJECTIVE To examine how diet , physical activity , and sedentary behaviors relate to overweight status in adolescents . DESIGN AND SETTING Baseline data from the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition Project , a r and omized controlled trial of adolescents to determine the effects of a clinic-based intervention on physical activity and dietary behaviors . PARTICIPANTS A total of 878 adolescents aged 11 to 15 years , 42 % of whom were from minority background s. MAIN OUTCOME MEASURE Centers for Disease Control and Prevention body mass index-for-age percentiles divided into 2 categories : normal weight ( or=85th percentile ) . RESULTS Overall , 45.7 % of the sample was classified as AR + O with a body mass index for age at the 85th percentile or higher . More girls from minority background s ( 54.8 % ) were AR + O compared with non-Hispanic white girls ( 42 % ) ( chi(2)(1 ) = 7.6 ; P = .006 ) . Bivariate analyses indicated that girls and boys in the AR + O group did fewer minutes per day of vigorous physical activity , consumed fewer total kilojoules per day , and had fewer total grams of fiber per day than those in the normal-weight group . Boys in the AR + O group also did fewer minutes per day of moderate physical activity and watched more minutes per day of television on nonschool days than normal-weight boys . Final multivariate models indicated that independent of socioeconomic status ( as assessed by household education level ) , girls had a greater risk of being AR + O if they were Hispanic or from another minority background ( odds ratio [ OR ] = 1.65 ; 95 % confidence interval [ CI ] , 1.09 - 2.49 ) and a reduced risk of being AR + O as minutes per day of vigorous physical activity increased ( OR = 0.93 ; 95 % CI , 0.89 - 0.97 ) . A low level of vigorous physical activity was the only significant risk factor for boys being AR + O ( OR = 0.92 ; 95 % CI , 0.89 - 0.95 ) . Analyses based on meeting behavioral guidelines supported these findings and showed that failing to meet the 60 min/d moderate to vigorous physical activity guideline was associated with overweight status for both girls and boys . In addition , boys who failed to meet sedentary behavior and dietary fiber guidelines were more likely to be overweight . CONCLUSIONS Of the 7 dietary and physical activity variables examined in this cross-sectional study , insufficient vigorous physical activity was the only risk factor for higher body mass index for adolescent boys and girls . Prospect i ve studies are needed to clarify the relative importance of dietary and physical activity behaviors on overweight in adolescence", "BACKGROUND It is unclear how moderate and vigorous intensities of physical activity ( PA ) are associated with cardiovascular fitness ( CVF ) and percentage of body fat ( % BF ) in adolescents . OBJECTIVE We tested the hypothesis that vigorous PA , to a greater degree than moderate PA , would be associated with better CVF and lower % BF . DESIGN This was a cross-sectional study of 421 black and white high school students ( x age : 16 y ) . PA was measured with 5 d of accelerometry and expressed in min/d of moderate or vigorous PA . CVF was measured with a multistage treadmill test and was expressed as the oxygen consumption at a heart rate of 170 bpm . % BF was measured with dual-energy X-ray absorptiometry . Multiple regressions were used to determine the degree to which variance in CVF and % BF was explained by PA , after control for age , sex , race , and the sex x race interaction . RESULTS A higher index for CVF was associated with higher amounts of moderate and vigorous PA ; more variance was explained by vigorous than by moderate PA . Lower % BF was associated with higher amounts of vigorous PA but not with the amount of moderate PA . CONCLUSION Black and white adolescents who engaged in relatively large amounts of free-living vigorous exercise were likely to be relatively fit and lean", "BACKGROUND Little is known about how the intensity of exercise influences cardiovascular fitness and body composition , especially in obese adolescents . OBJECTIVE Our goal was to determine the effects of physical training intensity on the cardiovascular fitness , percentage of body fat ( % BF ) , and visceral adipose tissue ( VAT ) of obese adolescents . DESIGN Obese 13 - 16-y-olds ( n = 80 ) were assigned to 1 ) biweekly lifestyle education ( LSE ) , 2 ) LSE + moderate-intensity physical training , or 3 ) LSE + high-intensity physical training . The intervention lasted 8 mo . Physical training was offered 5 d/wk , and the target energy expenditure for all subjects in physical training groups was 1047 kJ ( 250 kcal)/session . Cardiovascular fitness was measured with a multistage treadmill test , % BF with dual-energy X-ray absorptiometry , and VAT with magnetic resonance imaging . RESULTS The increase in cardiovascular fitness in the high-intensity physical training group , but not in the moderate-intensity group , was significantly greater than that in the LSE alone group ( P = 0.009 ) ; no other comparisons of the 3 groups were significant . Compared with the LSE alone group , a group composed of subjects in both physical training groups combined who attended training sessions > or=2 d/wk showed favorable changes in cardiovascular fitness ( P % BF ( P = 0.001 ) , and VAT ( P = 0.029 ) . We found no evidence that the high-intensity physical training was more effective than the moderate-intensity physical training in enhancing body composition . CONCLUSIONS The cardiovascular fitness of obese adolescents was significantly improved by physical training , especially high-intensity physical training . The physical training also reduced both visceral and total-body adiposity , but there was no clear effect of the intensity of physical training", "BACKGROUND Body mass index ( BMI ) during adolescence is predictive of BMI at adult age . However , BMI can not distinguish between lean and fat body mass . Skinfold thickness may be a better predictor of body fatness . OBJECTIVE The objective of this study was to evaluate the relations between BMI and skinfold thickness during adolescence and body fatness during adulthood . DESIGN We included 168 men and 182 women from the Amsterdam Growth and Health Longitudinal Study , a prospect i ve study that conducted 8 measurements of BMI and skinfold thickness between 1976 and 2000 . BMI and skinfold thickness during adolescence were analyzed in relation to adult body fatness measured at a mean age of 37 y with dual-energy X-ray absorptiometry . RESULTS None of the boys and 1.7 % of the girls were overweight at baseline , whereas the prevalence of high body fatness during adulthood was 29 % in men and 32 % in women . At the ages of 12 - 16 y , skinfold thickness was more strongly associated with adult body fatness than was BMI . Age-specific relative risks for a high level of adult body fatness varied between 2.3 and 4.0 in boys and between 2.1 and 4.3 in girls in the highest versus the lowest tertile of the sum of 4 skinfold thicknesses . For the highest tertile of BMI , the relative risk varied between 0.8 and 2.1 in boys and between 1.3 and 1.8 in girls . CONCLUSION Skinfold thickness during adolescence is a better predictor of high body fatness during adulthood than is BMI during adolescence", "BACKGROUND It is unclear whether physical activity energy expenditure ( PAEE ) predicts changes in body composition . OBJECTIVE The objective was to describe the independent associations between PAEE and changes in body composition in a population -based cohort . DESIGN This was a prospect i ve population -based study conducted in 739 ( 311 men and 428 women ) healthy middle-aged ( median age : 53.8 y ) whites . The median follow-up was 5.6 y. PAEE ( MJ/d ) was assessed by heart rate monitoring , individually calibrated by using the FLEX heart rate method . Fat mass ( FM ) and fat-free mass ( FFM ) were assessed by bioimpedance . RESULTS Body weight ( BW ) at follow-up was significantly related to baseline PAEE ( P BW increased by a mean ( + /-SD ) of 1.7 + /- 5.9 kg ( P FM was significantly associated with baseline PAEE ( P = 0.036 ) after adjustment for confounders . In the older cohort , BW did not change between baseline and follow-up . In this group , in contrast with the younger population , follow-up BW , FM , and FFM were all significantly and positively associated with baseline PAEE ( P PAEE predicts a change in FM in younger adults , who as a group gained weight in this study . In contrast , baseline PAEE in older adults -- who were on average weight stable -- is associated with a gain in BW , which was explained by an increase in FM and FFM", "PURPOSE Findings from prospect i ve studies on associations between physical activity and adiposity among youth are inconsistent . Our aim was to describe physical activity trajectories during secondary school and examine the association with change in adiposity in youth . METHODS Physical activity was measured in 20 survey cycles from 1999 to 2005 ; anthropometrics were measured in survey cycles 1 , 12 , and 19 . Individual growth curves modeling moderate-to-vigorous physical activity ( MVPA ) and vigorous physical activity ( VPA ) were estimated . Estimates of initial level and rate of decline in MVPA and VPA bouts per week were included as potential predictors of body fat% and body mass index using age- and sex-specific linear regression . RESULTS Complete data were available for 840 and 760 adolescents aged 12 - 13 years at baseline , followed from survey cycles 1 - 12 and 12 - 19 , respectively . Among girls , yearly declines of one MVPA and one VPA bout per week during earlier adolescence were associated with increases of 0.19 ( 95 % confidence interval [ CI ] , 0.02 - 0.36 ) and 0.47 ( 95 % CI , 0.015 - 0.92 ) units of body fat% , respectively . In boys , a yearly decline of one MVPA bout per week was associated with an increase of 0.38 ( 95 % CI , 0.05 - 0.70 ) units of body fat% during later adolescence . CONCLUSIONS Obesity prevention programs should include strategies to prevent declines in physical activity", "Background Active commuting is a good opportunity to accumulate physical activity ( PA ) across the lifespan that potentially might influence central body fat . We aim ed to examine the prospect i ve associations of active commuting at 11 , 15 and 18 years of age with central body fat at 18 years . Methods Participants were part of a large birth cohort study in Pelotas , Brazil ( n = 3,649 participants ) . Active commuting , leisure-time PA and income were self-reported at 11 , 15 and 18 years . Waist circumference and trunk fat mass were collected at 18 years with the use of a 3-dimensional photonic scanner and dual-energy X-ray absorptiometry , respectively . Results Active commuting at 11 years was not prospect ively associated with central body fat . However , we found that active commuting at 15 and 18 years were prospect ively and cross-sectionally associated with central body fat variables , respectively , in boys but not in girls . Also , boys in the highest tertile of accumulated active commuting ( i.e. , average of active commuting at 11 , 13 and 18 years ) were associated with −2.09 cm ( 95%CI : −3.24 ; −0.94 ) of waist circumference and −1.11 kg ( 95%CI : −1.74 ; −0.48 ) of trunk fat mass compared to boys in the lowest tertile . Analyses on changes in tertiles of active commuting from 11 and 15 years to 18 years with central body fat variables at 18 years showed that boys who remained consistently in the highest tertile or moved to a higher tertile had lower levels of central body fat compared to those consistently in the lowest tertile . Conclusions Active commuting throughout adolescence in boys , especially during middle and late adolescence , is associated with lower levels in central fatness before adulthood", "Abstract The aim of this study was to investigate the cross-sectional and prospect i ve associations between physical activity and body composition in adolescence . This is a prospect i ve study , including 4,103 adolescents belonging to the Pelotas ( Brazil ) 1993 birth cohort , who were followed up at the mean ages of 11.3 and 14.7 years . Sub sample analyses included 511 individuals with accelerometry and deuterium dilution data at 13.3 years . Sum of skinfolds at age 11.3 years was highly correlated with skinfolds at age 14.7 years ( rho = 0.74 , P Tracking of physical activity was considerably lower , although still significant ; the correlation was 0.24 ( P physical activity and body composition , neither in boys nor in girls . These None results were confirmed in the 511 individuals with accelerometry and deuterium data . We provide evidence of tracking of physical activity and particularly body composition during adolescence . Our results do not support the hypothesis that physical activity and fatness are strongly related in adolescents", "Objective To investigate associations between physical activity at age 12 and subsequent adiposity at age 14 . Design Prospect i ve birth cohort study with data collected between 2003 and 2007 . Setting Original recruitment in 1991 - 2 of 14 541 pregnant women living in the former County of Avon ( United Kingdom ) . Participants At age 12 , 11 952 children were invited to attend the research clinic . Of these , 7159 attended , and 4150 ( 1964 boys , 2186 girls ) provided sufficient data on exposure , outcome , and confounding variables . Main outcome measure Fat mass at age 14 , measured by dual emission x ray absorptiometry , associated with physical activity at age 12 , measured by accelerometry . Results Prospect i ve associations of fat mass at age 14 ( outcome ) with physical activity at age 12 ( exposure ) were strong for both total activity ( accelerometer counts/min ) and for daily amount of moderate-vigorous physical activity ( min/day ) . An extra 15 minutes of moderate-vigorous physical activity per day at age 12 was associated with lower fat mass at age 14 in boys ( by 11.9 % ( 95 % confidence interval 9.5 % to 14.3 % ) ) and girls ( by 9.8 % ( 6.7 % to 12.8 % ) ) . The proportion of physical activity due to moderate-vigorous physical activity was between 20 % and 30 % in boys and girls at the two ages . Conclusions Higher levels of physical activity , in particular activity of moderate to higher intensities , are prospect ively associated with lower levels of fat mass in early adolescence . Interventions to raise levels of physical activity in children are likely to be important in the fight against obesity", "Objectives To study correlates of change in BMI percentile and body fat among adolescent girls Design and Methods A longitudinal prospect i ve study following 265 girls from the Trial of Activity for Adolescent Girls ( TAAG ) cohort measured in 8th grade and during 10 and 11th grade or 11th and 12th grade . Twice during 2009 - 2011 girls wore an accelerometer and completed a food frequency question naire and 7-day diary documenting trips and food eaten away from home and school . Physical activity , BMI , and percent body fat were objective ly measured at each time point . Results Moderate to vigorous physical activity ( MVPA ) declined , but was not independently associated with changes in BMI percentile . Increased vigorous physical activity was associated with reductions in body fat . Diet was associated with both changes in BMI percentile and body fat . Girls who increased the percentage of caloric intake from snacks and desserts reduced their BMI percentile and body fat . Conclusions Some relationships between energy balance behaviors and BMI and body composition were counter-intuitive . While it is plausible that vigorous activity would result in reductions of body fat , until more accurate methods are devised to measure diet , the precise contribution of dietary composition to health will be difficult to assess", "BACKGROUND The role of physical activity in preventing obesity during adolescence remains unknown . We examined changes in activity in relation to changes in body-mass index ( BMI ) and adiposity in a cohort of 1152 black and 1135 white girls from the USA , who were followed up prospect ively from ages 9 or 10 to 18 or 19 years . METHODS BMI and sum of skinfold thickness were assessed annually , whereas habitual activity was assessed at years 1 ( baseline ) , 3 , 5 , and 7 - 10 . Each girls ' overall activity status was categorised as active , moderately active , or inactive . Longitudinal regression models examined associations between changes in activity and in overall activity status with changes in BMI and in sum of skinfold thickness . FINDINGS Each decline in activity of 10 metabolic equivalent [MET]-times per week was associated with an increase in BMI of 0.14 kg/m2 ( SE 0.03 ) and in sum of skinfold thickness of 0.62 mm ( 0.17 ) for black girls , and of 0.09 kg/m2 ( 0.02 ) and 0.63 mm ( 0.13 ) for white girls . At ages 18 or 19 years , BMI differences between active and inactive girls were 2.98 kg/m2 ( p sum of skinfold thickness . For moderately active girls , changes in BMI and sum of skinfold thickness were about midway between those for active and inactive girls . INTERPRETATION Changes in activity levels of US girls during adolescence significantly affected changes in BMI and adiposity . Thus , preventing the steep decline in activity during adolescence is an important method to reduce obesity", "Objective : This study aim ed to determine whether time spent outdoors was associated with objective ly measured physical activity , body mass index ( BMI ) z-score and overweight in elementary-school aged children , cross-sectionally and prospect ively over 3 years . Methods : Three-year cohort study with data collected during 2001 and 2004 . Nineteen r and omly selected state elementary schools across Melbourne , Australia . One hundred and eighty eight 5–6-year-old and 360 10–12-year-old children . Baseline parent reports of children 's time spent outdoors during warmer and cooler months , on weekdays and weekends . At baseline and follow-up , children 's moderate and vigorous physical activity ( MVPA ) was objective ly assessed by accelerometry , and BMI z-score and overweight was calculated from measured height and weight . Results : Cross-sectionally , each additional hour outdoors on weekdays and weekend days during the cooler months was associated with an extra 27 min week−1 MVPA among older girls , and with an extra 20 min week−1 MVPA among older boys . Longitudinally , more time outdoors on weekends predicted higher MVPA on weekends among older girls and boys ( 5 min week−1 ) . The prevalence of overweight among older children at follow-up was 27–41 % lower among those spending more time outdoors at baseline . Conclusion : Encouraging 10–12-year-old children to spend more time outdoors may be an effective strategy for increasing physical activity and preventing increases in overweight and obesity . Intervention research investigating the effect of increasing time outdoors on children 's physical activity and overweight is warranted", "PURPOSE To examine whether components of body composition ( size , fat mass , and fat-free mass ) were related to physical activity . METHODS A r and om sample of 60 eligible sixth grade girls at each of 36 schools ( six schools per region and six regions in total sample ) ; complete measurements on 1,553 girls . Physical activity was assessed over 6 d in each girl using an accelerometer , and body composition was assessed using a multiple regression equation using body mass index and triceps skinfold . Minutes of moderate-to-vigorous and vigorous physical activity were estimated from accelerometer counts per 30 s above threshold values determined from a previous study . RESULTS Significant inverse relationships were found for all measures of body size and composition and all physical activity indices . The combination of fat and fat-free mass expressed as a weight and as an index ( divided by height squared ) along with race , SES , site , and school were most highly associated with physical activity in multiple regression analysis , accounting for 14 - 15 % of the variance in physical activity . Fat mass was more closely related to moderate-to-vigorous physical activity ( MVPA ) and vigorous physical activity ( VPA ) than fat-free mass with higher st and ardized regression coefficients . CONCLUSION We conclude that both fat mass or fat mass index as well as fat-free mass or fat-free mass index make independent contributions in association with physical activity levels . These indices are recommended for future studies", "The purpose of this 7-yr prospect i ve longitudinal study was to examine if the level and consistency of leisure-time physical activity ( LTPA ) during adolescence affected the quantity and distribution of lean mass ( LM ) and fat mass ( FM ) at early adulthood . The study subjects were 202 Finnish girls who were 10 - 13 yr old at baseline . LM and FM of the total body ( TB ) , arms , legs , and trunk were assessed by dual-energy X-ray absorptiometry . Muscle cross-sectional area ( mCSA ) of the left leg was assessed by peripheral quantitative computed tomography . Scores of LTPA were obtained by question naire . Girls were divided into four groups comprising those with consistently low ( G(LL ) ) or consistently high ( G(HH ) ) physical activity , or those whose physical activity changed from low to high ( G(LH ) ) , or from high to low ( G(HL ) ) , over the 7 yr of follow-up . At baseline , no differences were found in LM , FM , and FM% among the groups in any of the body segments . By the end of the study G(HH ) and G(LH ) had higher values of LM of the TB , arms , legs , and trunk than that of the G(HL ) and G(LL ) groups ( P High FM% of the TB was associated with low level of LTPA , but no significant differences were found in the absolute amount of FM and mCSA among the LTPA groups . Our results suggest that a consistently high level of LTPA during the transition from prepuberty to early adulthood has a positive effect on lean mass gain in girls . Participating in 5 h of LTPA per week had a significant effect on FM% but not on the absolute amount of fat mass", "The objective of this study was to determine whether change in physical activity was associated with maintaining a healthy weight from childhood to adulthood . This prospect i ve cohort study examined 1,594 young Australian adults ( 48.9 % female ) aged 27 - 36 years who were first examined at age 9 - 15 years as part of a national health and fitness survey . BMI was calculated from measured height and weight , and physical activity was self-reported at both time points ; pedometers were also used at follow-up . Change in physical activity was characterized by calculating the difference between baseline and follow-up z-scores . Change scores were categorized as decreasing ( large , moderate ) , stable , or increasing ( large , moderate ) . Healthy weight was defined in childhood as a BMI less than international overweight cutoff points , and in adulthood as BMI Healthy weight maintainers were healthy weight at both time points . Compared with those who demonstrated large relative decreases in physical activity , females in all other groups were 25 - 37 % more likely to be healthy weight maintainers , although associations differed according to the physical activity measure used at follow-up and few reached statistical significance . Although younger males whose relative physical activity moderately or largely increased were 27 - 34 % more likely to be healthy weight maintainers than those whose relative physical activity largely decreased , differences were not statistically significant . In conclusion , relatively increasing and stable physical activity from childhood to adulthood was only weakly associated with healthy weight maintenance . Examining personal , social , and environmental factors associated with healthy weight maintenance will be an important next step in underst and ing why some groups avoid becoming overweight", "Body mass index ( BMI ) has various deficiencies as a measure of obesity , especially when the BMI measure is based on self-reported height and weight . BMI is an indirect measure of body fat compared with more direct approaches such as bioelectrical impedance . Moreover , BMI does not necessarily reflect the changes that occur with age . The proportion of body fat increases with age , whereas muscle mass decreases , but corresponding changes in height , weight and BMI may not reflect changes in body fat and muscle mass . Both the sensitivity and specificity of BMI have been shown to be poor . Additionally , the relation between BMI and percentage of body fat is not linear and differs for men and women . The consequences of the errors in the measurement of obesity with BMI depend on whether they are differential or nondifferential . Differential misclassification , a potentially greater problem in case – control and cross-sectional studies than in prospect i ve cohort studies , can produce a bias toward or away from the None . Nondifferential misclassification produces a bias toward the None for a dichotomous exposure ; for measures of exposure that are not dichotomous , the bias may be away from the None . In short , the use of BMI as a measure of obesity can introduce misclassification problems that may result in important bias in estimating the effects related to obesity", "PURPOSE To determine whether a significant relationship exists between fat mass ( FM ) development and physical activity ( PA ) and /or sugar-sweetened drink ( SD ) consumption in healthy boys and girls aged 8 - 19 yr . METHODS A total of 105 males and 103 females were assessed during childhood and adolescence for a maximum of 7 yr and a median of 5 yr . Height was measured biannually . Fat-free mass ( FFM ) and FM were assessed annually by dual x-ray absorptiometry ( DXA ) . PA was evaluated two to three times annually using the PAQ-C/A. Energy intake and SD were assessed using a 24-h dietary intake question naire also completed two to three times per year . Years from peak height velocity were used as a biological maturity age indicator . Multilevel r and om effects models were used to test the relationship . RESULTS When controlling for maturation , FFM , and energy intake adjusted for SD , PA level was negatively related to FM development in males ( P0.05 ) . In contrast , there was no relationship between SD and FM development of males or females ( P>0.05 ) . There was also no interaction effect between SD and PA ( P>0.05 ) with FM development . CONCLUSION This finding lends support to the idea that increasing PA in male youths aids in the control of FM development . Models employed showed no relationship between SD and FM in either gender", "Physical activity during childhood and adolescence may influence the development of childhood obesity and cardiovascular disease later in life . Research focused prospect ively on the effects of training on lipid levels in nonobese subjects , and studies using noninvasive measurements of subcutaneous and intraabdominal fat are lacking . It was hypothesized in nonobese sedentary adolescent males that a brief endurance-type exercise training intervention would reduce body fat and improve lipid profiles . Thirty-eight healthy , nonobese sedentary adolescent males ( mean age 16 + /- 0.7 years old ; 18 controls , 20 trained ) completed a 5-week prospect i ve , r and omized , controlled study . Adiposity was measured using magnetic resonance images of the thigh and abdomen ( subcutaneous abdominal adipose tissue [ SAAT ] and intraabdominal adipose tissue [ IAAT ] ) . Lipid measurements included serum triglycerides ( TG ) , total cholesterol ( TC ) , HDL and LDL cholesterol . There was no change in body weight in either control or training groups . Training led to small but significant reductions in thigh fat ( -4.6 + /- 1.5 % , p SAAT% ( 1.7 + /- 0.8 % , p IAAT% . Unexpectedly in the control group there were significant increases in thigh fat ( 5.2 + /- 1.7 % , p SAAT% ( 1.8 + /- 0.6 , p IAAT% ( 4.5 + /- 1.1 , p changes in adiposity were not accompanied by changes in circulating lipids . In nonobese adolescent males a brief period of endurance training led to reductions in body fat depots without weight change while body fat increased rapidly in the control group . Exercise training did not change lipid levels , the latter may require more sustained alterations in patterns of physical activity" ]

[ "Background —There is evidence that aerobic exercise improves functional capacity in patients with New York Heart Association ( NYHA ) class II and III chronic heart failure . However , it is unknown whether dancing is safe and able to improve functional capacity in patients with chronic heart failure . Methods and Results —We prospect ively studied 130 patients with stable chronic heart failure ( 107 men ; mean age , 59±11 years ) in New York Heart Association class II and III and left ventricle ejection fraction Patients were r and omized to supervised aerobic exercise training at 70 % of peak & OV0312;o2 3 times a week for 8 weeks ( group E , n=44 ) or to a dance protocol of alternate slow ( 5 minutes ) and fast ( 3 minutes ) waltz lasting 21 minutes ( group D , n=44 ) . A group that did not undergo exercise training served as control ( group C , n=42 ) . On study entry and at 8 weeks , all patients underwent cardiopulmonary exercise testing on a cycle ergometer until volitional fatigue , 2D-echo with Doppler , and endothelium-dependent dilation of the brachial artery . Heart rate was 111±15 bpm during exercise training and 113±19 bpm during dancing ( P=0.59 ) . Peak & OV0312;o2 , anaerobic threshold , & OV0312;e/&OV0312;co2 slope , and & OV0312;o2/W slope were all similarly improved in both E and D groups ( + 16 % and 18 % , 20 % and 21 % , 14 % and 15 % , 18 % and 19 % , respectively ; P not significant for all comparisons ; P controls ) . Endothelium-dependent relaxation was also similarly improved ( group E , from 2.6±1.3 % to 5.2±1.5 % , P The change in peak & OV0312;o2 in E and D groups was correlated with changes in peak velocity of early filling wave/peak velocity of late filling ratio ( r=−0.58 , P dilation ( r=0.64 , P events were rare in both E and D groups . Conclusions —In patients with stable chronic heart failure , waltz dancing is safe and able to improve functional capacity and endothelium-dependent dilation similar to traditional aerobic exercise training . Waltz dancing may be considered in clinical practice in combination with aerobic exercise training or as an alternative to it", "OBJECTIVE To determine the level of improvement , as regards pain , impact on fibromyalgia and depression , achieved by patients with fibromyalgia by comparing aquatic biodanza and stretching exercises . DESIGN R and omised controlled trial with two intervention groups . LOCATION Five health centres ( Almeria ) . PATIENTS A total of 82 fibromyalgia patients between 18 and 65 years old , diagnosed by American College of Rheumatology criteria , were included , with 12 patients declining to take part in the study . The 70 remaining patients were r and omly assigned to two groups of 35 patients each : aquatic biodanza and stretching exercises . Those who did not attend in at least 14 sessions or changed their treatment during the studio were excluded . The final sample consisted of 19 patients in aquatic biodanza group and 20 in stretching group . The limitations of the study included , the open evaluation design and a sample size reduced by defaults . MAIN MEASURES The outcome measures were sociodemographic data , quality of life ( Fibromyalgia Impact Question naire ) , pain ( McGill-Melzack question naire ; and Visual Analogue Scale ) , pressure algometry ( Wagner FPI10 algometer ) and depression ( Beck Inventory ) . These were carried out before and after a 12-week therapy . RESULTS The mean age of the sample was 55.41 years . The mean period from diagnosis was 13.44 years . The sample consisted mainly of housewives . There were significant differences ( P pain ( P fibromyalgia impact ( P depression ( P biodanza aquatic exercises improve pain and quality of life in fibromyalgia patients", "The present study has been carried out to investigate the effects of group-based Turkish folkloric dances on physical performance , balance , depression and quality of life ( QoL ) in 40 healthy adult elderly females over the age of 65 years . Subjects were r and omly allocated into Group 1 ( folkloric dance-based exercise ) and Group 2 ( control ) . A 8-week dance-based exercise program was performed . Outcome measures included a 20-m walk test , a 6-min walk test , stair climbing and chair rise time , Berg balance scale ( BBS ) , the Medical Outcomes Study ( MOS ) 36-item short form health survey ( SF-36 ) , and geriatric depression scale ( GDS ) question naires . In Group 1 statistically significant improvements were found in most of the physical performance tests , BBS and some SF-36 subscales after the exercise ( p SF-36 subscales and BBS score ( p physical performance , balance and QoL in elderly females . Application of folkloric dance specific to countries as an exercise program for elderly people may be helpful", "OBJECTIVE To evaluate the effect of a dance-based therapy on depressive symptoms among institutionalized older adults . DESIGN R and omized controlled trial . SETTING Nursing homes . PARTICIPANTS Older adults ( 60 years or older ) permanently living in a nursing home . INTERVENTION Exercise Dance for Seniors ( EXDASE ) Program design ed for the use in long-term care setting s performed once a week for 60 minutes for 3 months . MEASUREMENTS Baseline measures included sociodemographic characteristics , ability to perform basic as well as instrumental activities of daily living , basic mobility , self-rated health , and cognitive status . Outcome measures were collected before and after the intervention and included assessment of depressive symptoms using the geriatric depression scale ( GDS ) . RESULTS Comparison of participants with MMSE of 15 or higher showed that GDS scores in the intervention group significantly improved ( P = .005 ) , whereas the control group had a trend of further worsening of depressive symptoms ( P = .081 ) . GLM analysis documented highly statistically significant effect of dance therapy ( P = .001 ) that was not influenced by controlling for intake of antidepressants and nursing home location . Dance therapy may have decreased depressive symptoms even in participants with MMSE lower than 15 and result ed in more discontinuations and fewer prescriptions of antidepressants in the intervention group than in the control group . CONCLUSION This study provides evidence that dance-based exercise can reduce the amount of depressive symptoms in nursing home residents . In general , this form of exercise seems to be very suitable and beneficial for this population", "OBJECTIVES The main objectives of this experimental case series were to evaluate the feasibility of a modified dance-based exercise program with low ground impacts in persons with rheumatoid arthritis ( RA ) functional class III and to describe its effects on locomotor ability . The relationship between 3 locomotor tests and their responsiveness also were addressed . METHODS Ten female subjects participated in an 8-week exercise program . Locomotor ability was measured before and after the program using the 50-foot test of walking time , the 6-minute test of walking distance , and the locomotion biomechanical analysis . RESULTS All subjects showed a high compliance ( 92.5 % presence at sessions ) over the 8 weeks of exercise without any aggravation in disease status . They were able to train efficiently at moderate intensity up to 25 minutes . Significant improvements were found in locomotor ability , with a higher responsiveness measured by the locomotion biomechanical analysis , followed by the 6-minute gait test and the 50-foot gait test . Inconsistent relationships between tests suggested that different locomotor abilities are required during tests . CONCLUSION These results support the feasibility of a modified dance-based exercise program for persons with severe RA . With high levels of responsiveness , the detailed biomechanical analysis and the 6-minute gait test are recommended for the assessment of locomotor ability", "OBJECTIVES To determine whether tango dancing is as effective as mindfulness meditation in reducing symptoms of psychological stress , anxiety and depression , and in promoting well-being . DESIGN This study employed analysis of covariance ( ANCOVA ) and multiple regression analysis . PARTICIPANTS Ninety-seven people with self-declared depression were r and omised into tango dance or mindfulness meditation classes , or to control/waiting-list . SETTING classes were conducted in a venue suitable for both activities in the metropolitan area of Sydney , Australia . INTERVENTIONS Participants completed six-week programmes ( 1½h/week of tango or meditation ) . The outcome measures were assessed at pre-test and post-test . MAIN OUTCOME MEASURES Depression , Anxiety and Stress Scale ; The Self Esteem Scale ; Satisfaction with Life Scale , and Mindful Attention Awareness Scale . RESULTS Sixty-six participants completed the program and were included in the statistical analysis . Depression levels were significantly reduced in the tango ( effect size d=0.50 , p=.010 ) , and meditation groups ( effect size d=0.54 , p=.025 ) , relative to waiting-list controls . Stress levels were significantly reduced only in the tango group ( effect size d=0.45 , p=.022 ) . Attending tango classes was a significant predictor for the increased levels of mindfulness R(2)=.10 , adjusted R(2)=.07 , F (2,59)=3.42 , p=.039 . CONCLUSION Mindfulness-meditation and tango dance could be effective complementary adjuncts for the treatment of depression and /or inclusion in stress management programmes . Subsequent trials are called to explore the therapeutic mechanisms involved", "Objective : To compare the effects of traditional dancing with formal exercise training in terms of functional and cardiovascular benefits and motivation in patients with chronic heart failure . Design : R and omized controlled trial . Setting : Sports Medicine Laboratory . Subjects : Fifty-one Greek male patients aged 67.1±5.5 years with chronic heart failure of New York Heart Association ( NYHA ) class II – III , participated in an eight-month study . Interventions : They were r and omly assigned to either training with Greek traditional dances ( group A , n=18 ) , formal exercise training ( group B , n=16 ) or a sedentary control group ( group C , n=17 ) . Main measures : At entry and the end of the study all patients underwent cardiopulmonary exercise testing , functional ability assessment and quality of life evaluations . The Intrinsic Motivation Inventory was also used to assess participants ’ subjective experience . Results : After training group A showed increased peak oxygen consumption by 33.8 % ( 19.5 vs. 26.1 ml/kg/min , p ) , maximal treadmill tolerance by 48.5 % ( p a decreased Slope of expired minute ventilation for carbon dioxide output ( VE/VCO2 ) slope by 18 % ( p improvement in the quality of life indices . Intrinsic Motivation Inventory was increased only in group A by 26.2 % ( 3.08 vs. 3.87 , p Conclusions : Exercise training in chronic heart failure patients with Greek traditional dances led to functional and cardiovascular benefits similar to formal exercise training and to a higher level of motivation" ]

[ " Nursing staff are at risk for musculoskeletal injuries because of the physical nature of patient h and ling . The purpose of this study is to examine the effectiveness of a multifaceted minimal-lift environment on reported equipment use , musculoskeletal injury rates , and workers ’ compensation costs for patient-h and ling injuries . The pilot study consists of a mixed measures design , with both descriptive and quasi-experimental design elements . The intervention consists of engineering ( minimal-lift equipment ) , administrative ( nursing policy ) , and behavioral ( peer coach program ) controls . The comparison nursing unit has received engineering controls only . The convenience sample includes nursing staff employed on two medical-surgical nursing units , who provide direct patient care at least 50 % of the time . Nursing staff employed in a multifaceted lift environment report greater lift equipment use and experience less injury , with reduced worker ’s compensation costs", "Background Many employers and other stakeholders believe that health examinations of job applicants prevent occupational diseases and sickness absence . Objectives To evaluate the effectiveness of pre-employment examinations of job applicants in preventing occupational injury , disease and sickness absence compared to no intervention or alternative interventions . Search strategy We search ed CENTRAL ( The Cochrane Library ) , MEDLINE , EMBASE , CINAHL , PsycINFO and PEDro ( to December 2009 ) not restricted by date , language or publication type . Selection criteria We included r and omised controlled trials ( RCTs ) , controlled before-after studies ( CBA ) , and interrupted time-series ( ITS ) of health examinations to prevent occupational diseases and injuries in job applicants . Data collection and analysis Four review authors ( NM , ML , JV , ES ) independently selected studies , extracted data , and determined study quality . The studies were too heterogeneous for statistical pooling of results . Main results We included two RCTs , five CBA studies and two ITS . Seven studies with 5872 participants evaluated the screening process of pre-employment examinations and two studies with 2164 participants evaluated the measures to mitigate the risks found following the screening process . Of those studies that evaluated the screening process , one study found that a general examination did not reduce sick leave ( Mean Difference -0.1 95 % CI -0.5 to 0.3 ) but another study found that a more task focused examination did ( MD -36 95 % CI -68.3 to -3.8 ) . One study found that incorporation of a bronchial challenge test decreased occupational asthma ( trend change -2.6 95 % CI -3.6 to -1.5 ) . Three studies that included functional capacity evaluation found contradictory effects on injury rates and number of medical visits . The rates of rejecting job applicants varied from 2 % to 35 % . Neither of the two studies that evaluated risk mitigation found an increased injury rate after training or work accommodations had been implemented . We rated the evidence for all outcomes as very low quality . Authors ' conclusions There is very low quality evidence that pre-employment examinations that are specific to certain jobs or health problems could reduce occupational disease , injury , or sickness absence . This supports the current policy to restrict pre-employment examinations to job-specific examinations . More studies are needed that take into account the harms of rejecting job applicants", "Back injuries are a serious problem for nursing personnel who perform frequent patient-h and ling activities . Common prevention strategies include body mechanics education , technique training , and ergonomic interventions such as the introduction of assistive equipment . This investigation assessed and compared the effectiveness of two patient-h and ling approaches to reducing injury risk . One strategy involved using improved patient-h and ling technique with existing equipment , and the other approach aim ed at eliminating manual patient h and ling through the use of additional mechanical and other assistive equipment . Both intervention arms received training in back care , patient assessment , and use of the equipment available on their particular wards . An analysis of compliance with interventions and the effects of patient-h and ling methods on both peak and cumulative spinal compression and shear during various tasks was conducted . Results showed greater compliance with interventions that incorporated new assistive patient-h and ling equipment , as opposed to those consisting of education and technique training alone . In several tasks , subjects who were untrained or non-compliant with interventions experienced significantly higher peak spinal loading . However , patient-h and ling tasks conducted with the aid of assistive equipment took substantially longer than those performed manually . This , along with variations in techniques , led to increases in cumulative spinal loading with the use of patient-h and ling equipment on some tasks . Thus , the use of mechanical assistive devices may not always be the best approach to reducing back injuries in all situations . No single intervention can be recommended ; instead all patient-h and ling tasks should be examined separately to determine which methods maximize reductions in both peak and cumulative lumbar forces during a manoeuver", "BACKGROUND Until recently , no evidence -based criteria were available to determine the work-relatedness of low back pain ( LBP ) in an individual worker . Incidence figures for LBP that can be qualified as occupational disease ( OD ) are scarce . We studied the trend in the number of OD notifications due to LBP in the Netherl and s and estimated incidence rates of LBP-related OD notifications . METHODS We developed an instrument for the assessment of work-relatedness of non-specific LBP ( NLBP ) in 2004 , accompanied by an OD registration guideline . We analysed the trend in LBP-related OD notifications in the register of the Netherl and s Centre for Occupational Diseases ( NCOD ) from 2004 to 2011 . We estimated incidence rates for LBP-related OD notifications with data from a prospect i ve cohort study , performed by NCOD in 2009 - 2011 . RESULTS After implementation of the instrument and guideline , we noticed a huge increase in numbers of LBP-related OD-notifications , from 0.7 % of all notified ODs in 2004 , via 8.6 % in 2005 and 13.6 % in 2008 , to 9.1 % in 2011 . We estimated the incidence rate of ODs due to LBP at 24.1 per 100,000 worker years ( 19.2 for NLBP ) , with a large difference between men and women ( 31.3 and 3.2 , respectively ) . CONCLUSIONS The instrument for the assessment of work-relatedness of NLBP played an important role in the recognition of LBP-related ODs . It provides a basis for a more uniform and objective evaluation of the role of work-related risk factors in the occurrence of NLBP . This knowledge can be used to initiate or direct preventive actions towards subgroups with higher incidence rates", "This study was funded in part by NIH grant AR36308 The authors thank the employees of the United States Postal Service and the American Postal Workers Union ( APWU ) , Boston Metro Area Local , and Maith and lers Local 301 for their help and cooperation ; therapists from the Department of Rehabilitation Services , Bngham and Women 's Hospital for help in training workers ; and Ms Nancy Tanner for", "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", "Objective To report the annual incidence of occupational diseases ( ODs ) in economic sectors in The Netherl and s. Methods In a 5-year prospect i ve cohort study ( 2009–2013 ) , occupational physicians were asked to participate in a sentinel surveillance system for OD notification . The inclusion criteria for participation were ( 1 ) covering a population of employees , ( 2 ) reporting the economic sectors and the size of their employee population and ( 3 ) willingness to report all diagnosed ODs . In this study , an OD was defined as a disease with a specific clinical diagnosis that was predominantly caused by work-related factors . The economic sectors ( n=21 ) were defined according the NACE ( Nomenclature des Activités Économiques dans la Communauté Européenne ) classification . Results In a total working population of 514 590 employees , 1782 ODs were reported over 12 months in 2009 . The estimated annual incidence for any OD was 346 ( 95 % CI 330 to 362 ) per 100 000 worker-years . Of all the ODs , mental diseases were reported most frequently ( 41 % ) , followed by musculoskeletal ( 39 % ) , hearing ( 11 % ) , infectious ( 4 % ) , skin ( 3 % ) , neurological ( 2 % ) and respiratory ( 2 % ) diseases . The four economic sectors with the highest annual incidences per 100 000 workers were construction ( 1127 ; 95 % CI 1002 to 1253 ) , mining and quarrying ( 888 ; 95 % CI 110 to 1667 ) , water and waste processing ( 832 ; 95 % CI 518 to 1146 ) and transport and storage ( 608 ; 95 % CI 526 to 690 ) . Conclusion ODs are reported in all economic sectors in The Netherl and s. Up to 91 % of all ODs are mental , musculoskeletal and hearing diseases . Efforts to increase the effective assessment of ODs and compliance in reporting activities enhance the usability of incidence figures for the government , employers and workers" ]

[ "Background To determine whether an internet-based mentoring program can improve glycemic control in subjects with type 1 diabetes mellitus ( T1DM ) . Methods Subjects with T1DM on intensive insulin therapy and with hemoglobin A1c ( HbA1c ) ≥8.0 % were r and omized to mentored ( glucometer transmission with feedback from mentors ) or control ( glucometer transmission without feedback ) groups and were examined for 12 weeks . Five mentors were interviewed and selected , of which two were T1DM patients themselves and three were parents with at least one child diagnosed with T1DM since more than 5 years ago . Results A total of 57 T1DM adult subjects with a mean duration after being diagnosed with diabetes of 7.4 years were recruited from Samsung Medical Center . Unfortunately , the mentored group failed to show significant improvements in HbA1c levels or other outcomes , including the quality of life , after completion of the study . However , the mentored group monitored their blood glucose ( 1.41 vs. 0.30 ) and logged into our website ( http://ubisens.co.kr/ ) more frequently ( 20.59 times vs. 5.07 times ) than the control group . Conclusion A 12-week internet-based mentoring program for T1DM patients with inadequate glycemic control did not prove to be superior to the usual follow-up . However , the noted increase in the subjects ' frequency of blood glucose monitoring may lead to clinical benefits", "AIMS To assess Sweet Talk , a text-messaging support system design ed to enhance self-efficacy , facilitate uptake of intensive insulin therapy and improve glycaemic control in paediatric patients with Type 1 diabetes . METHODS One hundred and twenty-six patients fulfilled the eligibility criteria ; Type 1 diabetes for > 1 year , on conventional insulin therapy , aged 8 - 18 years . Ninety-two patients were r and omized to conventional insulin therapy ( n = 28 ) , conventional therapy and Sweet Talk ( n = 33 ) or intensive insulin therapy and Sweet Talk ( n = 31 ) . Goal - setting at clinic visits was reinforced by daily text-messages from the Sweet Talk software system , containing personalized goal -specific prompts and messages tailored to patients ' age , sex and insulin regimen . RESULTS HbA(1c ) did not change in patients on conventional therapy without or with Sweet Talk ( 10.3 + /- 1.7 vs. 10.1 + /- 1.7 % ) , but improved in patients r and omized to intensive therapy and Sweet Talk ( 9.2 + /- 2.2 % , 95 % CI -1.9 , -0.5 , P Sweet Talk was associated with improvement in diabetes self-efficacy ( conventional therapy 56.0 + /- 13.7 , conventional therapy plus Sweet Talk 62.1 + /- 6.6 , 95 % CI + 2.6 , + 7.5 , P = 0.003 ) and self-reported adherence ( conventional therapy 70.4 + /- 20.0 , conventional therapy plus Sweet Talk 77.2 + /- 16.1 , 95 % CI + 0.4 , + 17.4 , P = 0.042 ) . When surveyed , 82 % of patients felt that Sweet Talk had improved their diabetes self-management and 90 % wanted to continue receiving messages . CONCLUSIONS Sweet Talk was associated with improved self-efficacy and adherence ; engaging a classically difficult to reach group of young people . While Sweet Talk alone did not improve glycaemic control , it may have had a role in supporting the introduction of intensive insulin therapy . Scheduled , tailored text messaging offers an innovative means of supporting adolescents with diabetes and could be adapted for other health-care setting s and chronic diseases", "BACKGROUND Telehome care has been proposed as a solution to the challenges of providing effective and affordable care for patients with diabetes . METHODS A total of 100 adult patients with type 2 diabetes-divided between insulin and noninsulin requiring-was enrolled in a r and omized , controlled trial aim ed at investigating the effects of telehome monitoring . The experimental group ( n = 50 ) received an in-home wireless glucose monitor and transmitter , whereas the control group ( n = 50 ) was instructed to follow the conventional arrangement . RESULTS There was an overall reduction in HbA1c values in both experimental and control groups after 6 months . A significant difference in HbA1c values between the groups was observed only among the noninsulin-requiring patients ( decline from 6.95 % ± 0.82 % to 6.66 % ± 0.86 % in IB vs. 7.21 % ± 2.02 % to 7.2 % ± 1.86 % in IIB ; p = 0.02 ) . The experimental group reported considerably less hyperglycemic and hypoglycemic events . The profile of the patient who benefited the most from telemonitoring consisted of older , more educated patient who had acquired the disease relatively recently , and who spends most of the time at home . The experimental group had higher overall scores on quality of life measures and sense of control over diabetes . There was a positive association between educational attainment and ability to use the telemonitoring system without help ( p = 0.045 ) . CONCLUSIONS Although not conclusive because of the small sample and short observation period , the study suggests that telehome monitoring is an effective tool in controlling type 2 diabetes in a primary care setting", "OBJECTIVE To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS For this study , 104 patients with diabetes and HbA(1c ) ( A1C ) > or = 9.0 % who received their care at a Department of Veterans Affairs medical center were recruited . All participants completed a diabetes education class and were r and omized to continue with their usual care ( n = 52 ) or receive web-based care management ( n = 52 ) . The web-based group received a notebook computer , glucose and blood pressure monitoring devices , and access to a care management website . The website provided educational modules , accepted uploads from monitoring devices , and had an internal messaging system for patients to communicate with the care manager . RESULTS Participants receiving web-based care management had lower A1C over 12 months ( P care . Persistent website users had greater improvement in A1C when compared with intermittent users ( -1.9 vs. -1.2 % ; P = 0.051 ) or education and usual care ( -1.4 % ; P website data uploads was associated with a larger decline in A1C ( highest tertile -2.1 % , lowest tertile -1.0 % ; P Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure ( P HDL cholesterol rose and triglycerides fell in the web-based group ( P Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes", "OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year", "BACKGROUND Blood glucose monitoring is an important component of diabetes self-management for individuals with insulin-treated diabetes . Although patient-maintained logbooks are routinely used , glucose values may be inaccurately recorded or not recorded at all . Electronic logbooks may help overcome such problems . We conducted a r and omized , controlled trial ( RCT ) to compare glycemic control in insulin-treated participants using integrated glucose meters and electronic logbooks ( Electronic Group ) with participants using conventional meters and paper logbooks ( Paper Group ) , and to determine persistence of glycemic improvements during long-term observational follow-up . METHODS After a 4-week run-in , adult and pediatric participants ( n = 205 ) with stable hemoglobin A(1C ) ( A1C ) > or=8.0 % were r and omized , and their logbook data and A1C were monitored every 4 weeks for 16 weeks . After the RCT , patients selected their monitoring systems and resumed usual care . The four result ing subgroups , defined by whether patients continued or changed monitoring systems , were reassessed after 26 - 65 weeks . RESULTS During the RCT , mean A1C decreased -0.27 % in the Paper Group and -0.35 % in the Electronic Group . Repeated- measures analysis revealed that the mean decrease was significantly greater in the Electronic than the Paper Group ( P = 0.022 ) . From r and omization through observational follow-up , participants consistently using integrated meters/logbooks had an A1C decrease of -0.36 % ( P = 0.008 ) , whereas participants using conventional meters/logbooks throughout or switching meters returned to pre-enrollment A1C levels . CONCLUSIONS Compared to conventional monitoring systems , use of an integrated meter and electronic logbook result ed in modest , but significant and sustained , improvement in A1C in insulin-treated patients with suboptimal glycemic control during an RCT and observational follow-up", "OBJECTIVE To evaluate a clinic-based multimedia intervention for diabetes education targeting individuals with low health literacy levels in a diverse population . RESEARCH DESIGN AND METHODS Five public clinics in Chicago , Illinois , participated in the study with computer kiosks installed in waiting room areas . Two hundred forty-four subjects with diabetes were r and omized to receive either supplemental computer multimedia use ( intervention ) or st and ard of care only ( control ) . The intervention includes audio/video sequences to communicate information , provide psychological support , and promote diabetes self-management skills without extensive text or complex navigation . HbA(1c ) ( A1C ) , BMI , blood pressure , diabetes knowledge , self-efficacy , self-reported medical care , and perceived susceptibility of complications were evaluated at baseline and 1 year . Computer usage patterns and implementation barriers were also examined . RESULTS Complete 1-year data were available for 183 subjects ( 75 % ) . Overall , there were no significant differences in change in A1C , weight , blood pressure , knowledge , self-efficacy , or self-reported medical care between intervention and control groups . However , there was an increase in perceived susceptibility to diabetes complications in the intervention group . This effect was greatest among subjects with lower health literacy . Within the intervention group , time spent on the computer was greater for subjects with higher health literacy . CONCLUSIONS Access to multimedia lessons result ed in an increase in perceived susceptibility to diabetes complications , particularly in subjects with lower health literacy . Despite measures to improve informational access for individuals with lower health literacy , there was relatively less use of the computer among these participants", "OBJECTIVE To improve quality and efficiency of care for elderly patients with type 2 diabetes , we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare ( u-healthcare ) service , which is an individualized health management system using advanced medical information technology . RESEARCH DESIGN AND METHODS We conducted a 6-month r and omized , controlled clinical trial involving 144 patients aged > 60 years . Participants were r and omly assigned to receive routine care ( control , n = 48 ) , to the self-monitored blood glucose ( SMBG , n = 47 ) group , or to the u-healthcare group ( n = 49 ) . The primary end point was the proportion of patients achieving A1C without hypoglycemia at 6 months . U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient ’s mobile phone . Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server . Once the data are transferred to the server , an automated system , the CDSS rule engine , generates and sends patient-specific messages by mobile phone . RESULTS After 6 months of follow-up , the mean A1C level was significantly decreased from 7.8 ± 1.3 % to 7.4 ± 1.0 % ( P proportion of patients with A1C was 30.6 % in the u-healthcare group , 23.4 % in the SMBG group ( 23.4 % ) , and 14.0 % in the control group ( P u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients", "OBJECTIVE Large amounts of time and effort are needed to implement an Internet-based glucose monitoring system ( IBGMS ) in the clinical setting . This study was design ed using research experience that was developed while implementing an IBGMS in Korea , and the research platform was modified to evaluate the efficacy of an IBGMS in controlling blood sugar in the Chinese population . METHODS A r and omized , open-label , parallel group design was used to evaluate the efficacy of an IBGMS among Chinese subjects with type 2 diabetes . Over a 6-month period , 182 subjects were evaluated in the IBGMS ( n = 92 ) or control ( n = 90 ) groups . RESULTS After 3 months , the control group 's HbA1c levels were reduced from 8.0 % ± 0.8 % to 7.3 % ± 1.2 % ( p and IBGMS groups were significant at the 3-month ( p = 0.002 ) and 6-month ( p HbA1c levels in the control group increased slightly ( 7.3 % ± 1.1 % to 7.4 % ± 1.3 % , p = 0.605 ) , and the HbA1c levels in the IBGMS group decreased slightly ( 6.9 % ± 0.7 % to 6.7 % ± 0.7 % , p = 0.081 ) . CONCLUSIONS The IBGMS was effective in improving blood sugar levels among patients with diabetes . Therefore , IBGMS experience can be effectively transferred between institutions and countries", "Background Diabetes requires extensive self-care and comprehensive knowledge , making patient education central to diabetes self-management . Web 2.0 systems have great potential to enhance health information and open new ways for patients and practitioners to communicate . Objective To develop a Web portal design ed to facilitate self-management , including diabetes-related information and social networking functions , and to study its use and effects in pediatric patients with diabetes . Methods A Web 2.0 portal was developed in collaboration with patients , parents , and practitioners . It offered communication with local practitioners , interaction with peers , and access to relevant information and services . Children and adolescents with diabetes in a geographic population of two pediatric clinics in Sweden were r and omized to a group receiving passwords for access to the portal or a control group with no access ( n=230 ) for 1 year . All subjects had access during a second study year . Users ’ activity was logged by site and page visits . Health-related quality of life ( HRQOL ) , empowerment ( DES ) , and quality of information ( QPP ) question naires were given at baseline and after 1 and 2 study years . Clinical data came from the Swedish pediatric diabetes quality registry SWEDIABKIDS . Results There was a continuous flow of site visits , decreasing in summer and Christmas periods . In 119/233 families ( 51 % ) , someone visited the portal the first study year and 169/484 ( 35 % ) the second study year . The outcome variables did not differ between intervention and control group . No adverse treatment or self-care effects were identified . A higher proportion of mothers compared to fathers visited once or more the first year ( P diabetes duration ( P=.006 ) , were younger ( P=.008 ) , had lower HbA1c after 1 year of access ( P=.010 ) , and were more often girls ( P Peer interaction seems to be a valued aspect . Conclusions The Web 2.0 portal may be useful as a complement to traditional care for this target group . Widespread use of a portal would need integration in routine care and promotion by diabetes team members . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N):92107365 ; http://www.controlled-trials.com/IS RCT N92107365/ ( Archived by WebCite at http://webcitation.org/6IkiIvtSb )", "Background Virtual world environments have the potential to increase access to diabetes self-management interventions and may lower cost . Objective We tested the feasibility and comparative effectiveness of a virtual world versus a face-to-face diabetes self-management group intervention . Methods We recruited African American women with type 2 diabetes to participate in an 8-week diabetes self-management program adapted from Power to Prevent , a behavior-change in-person group program for African Americans with diabetes or pre-diabetes . The program is social cognitive theory – guided , evidence -based , and culturally tailored . Participants were r and omized to participate in the program via virtual world ( Second Life ) or face-to-face , both delivered by a single intervention team . Blinded assessors conducted in-person clinical ( HbA1c ) , behavioral , and psychosocial measurements at baseline and 4-month follow-up . Pre-post differences within and between intervention groups were assessed using t tests and chi-square tests ( two-sided and intention-to-treat analyses for all comparisons ) . Results Participants ( N=89 ) were an average of 52 years old ( SD 10 ) , 60 % had ≤high school , 82 % had household incomes . Overall session attendance was similar across the groups ( 6.8/8 sessions , P=.90 ) . Compared to face-to-face , virtual world was slightly superior for total activity , light activity , and inactivity ( P=.05 , P=.07 , and P=.025 , respectively ) . HbA1c reduction was significant within face-to-face ( −0.46 , P=02 ) but not within virtual world ( −0.31 , P=.19 ) , although there were no significant between group differences in HbA1c ( P=.52 ) . In both groups , 14 % fewer patients had post-intervention HbA1c ≥9 % ( virtual world P=.014 ; face-to-face P=.002 ) , with no significant between group difference ( P=.493 ) . Compared to virtual world , face-to-face was marginally superior for reducing depression symptoms ( P=.051 ) . The virtual world intervention costs were US $ 1117 versus US $ 931 for face-to-face . Conclusions It is feasible to deliver diabetes self-management interventions to inner city African American women via virtual worlds , and outcomes may be comparable to those of face-to-face interventions . Further effectiveness research is warranted . Trial Registration Clinical Trials.gov NCT01340079 ; http:// clinical trials.gov/show/NCT01340079 ( Archived by WebCite at http://www.webcitation.org/6T2aSvmka )", "BACKGROUND Behavioral research to improve lifestyle in broadly defined population s of patients with type 2 diabetes is limited . OBJECTIVE We evaluated a behavioral intervention featuring technology-based self-monitoring on biophysiologic outcomes of glycemic control and markers of cardiovascular risk . DESIGN In this single-site , r and omized clinical trial , participants were stratified by good and poor glycemic control ( glycated hemoglobin and r and omized within strata . Measurements were obtained at 0 , 3 , and 6 months . PARTICIPANTS / SETTING Self-referred , community-dwelling adults with type 2 diabetes mellitus . INTERVENTION The intervention group received Social Cognitive Theory-based counseling paired with technology-based self-monitoring , and results were compared with an attention control group . MAIN OUTCOME MEASURES Glycated hemoglobin , fasting serum glucose , lipid levels , blood pressure , weight , body mass index , and waist circumference were evaluated . STATISTICAL ANALYSES PERFORMED Mean differences within and between r and omization groups were compared over time . Intervention effects over time were estimated using r and om intercept models . RESULTS Two hundred ninety-six subjects were r and omized , 256 ( 86.5 % ) completed 3-month and 246 ( 83.1 % ) completed 6-month assessment s. Glycated hemoglobin was reduced in the intervention group by 0.5 % at 3 months and 0.6 % at 6 months ( P baseline glycated hemoglobin ≥8 % and estimated glomerular filtration rate ≥60 mL/min , glycated hemoglobin was reduced in the intervention group by 1.5 % at 3 months and 1.8 % at 6 months ( P reduction in glycated hemoglobin of 0.29 % was not significant . CONCLUSIONS Two behavioral approaches to improving general lifestyle management in individuals with type 2 diabetes mellitus were effective in improving glycemic control , but no significant between-group differences were observed", "OBJECTIVE We hypothesized that people with type 2 diabetes in an online diabetes self-management program , compared with usual-care control subjects , would 1 ) demonstrate reduced A1C at 6 and 18 months , 2 ) have fewer symptoms , 3 ) demonstrate increased exercise , and 4 ) have improved self-efficacy and patient activation . In addition , participants r and omized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement . RESEARCH DESIGN AND METHODS A total of 761 participants were r and omized to 1 ) the program , 2 ) the program with e-mail reinforcement , or 3 ) were usual-care control subjects ( no treatment ) . This sample included 110 American Indians/Alaska Natives ( AI/ANs ) . Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups . RESULTS At 6 months , A1C , patient activation , and self-efficacy were improved for program participants compared with usual care control subjects ( P health or behavioral indicators . The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects . The subgroup with initial A1C > 7 % demonstrated stronger improvement in A1C ( P = 0.01 ) . At 18 months , self-efficacy and patient activation were improved for program participants . A1C was not measured . Reinforcement showed no improvement . CONCLUSIONS An online diabetes self-management program is acceptable for people with type 2 diabetes . Although the results were mixed they suggest 1 ) that the program may have beneficial effects in reducing A1C , 2 ) AI/AN population s can be engaged in and benefit from online interventions , and 3 ) our follow-up reinforcement appeared to have no value", "Blood glucose ( BG ) monitoring ( BGM ) is an important component of diabetes management . New wireless technologies may facilitate BGM and help to optimize glycemic control . We evaluated an integrated wireless approach with and without a motivational game in youth with diabetes . Forty youth , 8 - 18 years old , each received a h and held device fitted with a wireless modem and diabetes data management software , plus a wireless-enabled BG monitor . Half were r and omized to receive the new technologies along with an integrated motivational game in which the participants would guess a BG level following collection of three earlier readings ( Game Group ) . BG data , insulin doses , and carbohydrate intake were displayed graphically prior to the glucose estimation . The other group received the new technologies alone ( Control Group ) . Both groups were instructed to perform BGM four times daily and transmit their data to a central server via the wireless modem . Feasibility of implementation and outcomes were ascertained after 4 weeks . Ninety-three percent of participants successfully transmitted their data wirelessly to the server . The Game Group transmitted significantly more glucose values than the Control Group ( P less hyperglycemia ( glucose > /=13.9 mmol/L or > /=250 mg/dL ) than the Control Group ( P diabetes knowledge over the 4-week trial ( P hemoglobin A1C values pediatric population with diabetes can successfully implement new technologies to facilitate BGM . Use of a motivational game appears to increase the frequency of monitoring , reduce the frequency of hyperglycemia , and improve diabetes knowledge , and may help to optimize glycemic control", "OBJECTIVE The study objective was to evaluate how the use of a pervasive blood glucose monitoring ( BGM ) technology relates to glycemic control , report of self-care behavior , and emotional response to BGM of children with type 1 diabetes and their parents . RESEARCH DESIGN AND METHODS Forty-eight children aged less than 12 years ( mean 8.8 years ) with type 1 diabetes were r and omly assigned to one of two study groups , a control group ( conventional care without technology ) or an experimental group ( conventional care with technology ) , and followed for 12 months . Families in the experimental group were given the Automated Diabetes Management System ( ADMS ) , which automatically collects blood glucose ( BG ) values and sends to parent(s ) a 21-day BG trending report via e-mail each night . Measures of glycemic control ( HbA1c ) were collected at baseline and at quarterly diabetes clinic visits ; BGM effect and diabetes self-care behavior measures were obtained at the baseline , 6-month , and 12-month visits . RESULTS Children in the experimental group had significantly ( P = 0.01 ) lower HbA1c at 12 months ( 7.44 ± 0.94 , −0.35 from baseline ) than controls ( 8.31 ± 1.24 , + 0.15 from baseline ) . Improvement in HbA1c was more profound in families using the ADMS more frequently . In addition , in these families , parents showed a significant improvement in BGM effect ( P = 0.03 ) and children became more meticulous in diabetes self-care ( P = 0.04 ) . Children in both experimental and control groups experienced no change in their emotional response to BGM . CONCLUSIONS Using the ADMS 1–3 times/week may help children with type 1 diabetes improve glycemic control and gain diabetes self-management skills , as well as improve the BGM effect of parents ", "We have demonstrated previously that an individualized health management system using advanced medical information technology , named ubiquitous (u)-healthcare , was helpful in achieving better glycemic control than routine care . Recently , we generated a new u-healthcare system using a voice inception technique for elderly diabetic patients to communicate information about their glucose control , physical activity , and diet more easily . In a r and omized clinical trial , 70 diabetic patients aged 60–85 years were assigned r and omly to a st and ard care group or u-healthcare group for 6 months . The primary end points were the changes in glycated hemoglobin ( HbA1c ) and glucose fluctuation assessed by the mean amplitude glycemic excursion ( MAGE ) . Changes in body weight , lifestyle , and knowledge about diabetes were also investigated . After 6 months , the HbA1c levels decreased significantly in the u-healthcare group ( from 8.6 ± 1.0 % to 7.5 ± 0.6 % ) compared with the st and ard care group ( from 8.7 ± 0.9 % to 8.2 ± 1.1 % , P The MAGE decreased more in the u-healthcare group than in the st and ard care group . Systolic blood pressure and body weight decreased and liver functions improved in the u-healthcare group , but not in the st and ard care group . The u-healthcare system with voice inception technique was effective in achieving glycemic control without hypoglycemia in elderly diabetic patients ( Clinical trials.gov : NCT01891474 )", "OBJECTIVE —To test Web-based care management of glycemic control using a shared electronic medical record with patients who have type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a trial of 83 adults with type 2 diabetes r and omized to receive usual care plus Web-based care management or usual care alone between August 2002 and May 2004 . All patients had GHb ≥7.0 % , had Web access from home , and could use a computer with English language –based programs . Intervention patients received 12 months of Web-based care management . The Web-based program included patient access to electronic medical records , secure e-mail with providers , feedback on blood glucose readings , an educational Web site , and an interactive online diary for entering information about exercise , diet , and medication . The primary outcome was change in GHb . RESULTS —GHb levels declined by 0.7 % ( 95 % CI 0.2−1.3 ) on average among intervention patients compared with usual-care patients . Systolic blood pressure , diastolic blood pressure , total cholesterol levels , and use of in-person health care services did not differ between the two groups . CONCLUSIONS —Care management delivered through secure patient Web communications improved glycemic control in type 2 diabetes", "Numerous diabetes-management systems and programs for improving glycemic control to meet guideline targets have been proposed , using IT technology . But all of them allow only limited-or no-real-time interaction between patients and the system in terms of system response to patient input ; few studies have effectively assessed the systems ' usability and feasibility to determine how well patients underst and and can adopt the technology involved . DialBetics is composed of 4 modules : ( 1 ) data transmission module , ( 2 ) evaluation module , ( 3 ) communication module , and ( 4 ) dietary evaluation module . A 3-month r and omized study was design ed to assess the safety and usability of a remote health- data monitoring system , and especially its impact on modifying patient lifestyles to improve diabetes self-management and , thus , clinical outcomes . Fifty-four type 2 diabetes patients were r and omly divided into 2 groups , 27 in the DialBetics group and 27 in the non-DialBetics control group . HbA1c and fasting blood sugar ( FBS ) values declined significantly in the DialBetics group : HbA1c decreased an average of 0.4 % ( from 7.1 ± 1.0 % to 6.7 ± 0.7 % ) compared with an average increase of 0.1 % in the non-DialBetics group ( from 7.0 ± 0.9 % to 7.1 ± 1.1 % ) ( P = .015 ) ; The DialBetics group FBS decreased an average of 5.5 mg/dl compared with a non-DialBetics group average increase of 16.9 mg/dl ( P = .019 ) . BMI improvement-although not statistically significant because of the small sample size-was greater in the DialBetics group . DialBetics was shown to be a feasible and an effective tool for improving HbA1c by providing patients with real-time support based on their measurements and inputs", "OBJECTIVE Widespread use of carbohydrate counting is limited by its complex education . In this study we compared a Diabetes Interactive Diary ( DID ) with st and ard carbohydrate counting in terms of metabolic and weight control , time required for education , quality of life , and treatment satisfaction . RESEARCH DESIGN AND METHODS Adults with type 1 diabetes were r and omly assigned to DID ( group A , n = 67 ) or st and ard education ( group B , n = 63 ) and followed for 6 months . A subgroup also completed the SF-36 Health Survey ( SF-36 ) and World Health Organization-Diabetes Treatment Satisfaction Question naire ( WHO-DTSQ ) at each visit . RESULTS Of 130 patients ( aged 35.7 ± 9.4 years ; diabetes duration 16.5 ± 10.5 years ) , 11 dropped out . Time for education was 6 h ( range 2–15 h ) in group A and 12 h ( 2.5–25 h ) in group B ( P = 0.07 ) . A1C reduction was similar in both groups ( group A from 8.2 ± 0.8 to 7.8 ± 0.8 % and group B from 8.4 ± 0.7 to 7.9 ± 1.1 % ; P = 0.68 ) . Nonsignificant differences in favor of group A were documented for fasting blood glucose and body weight . No severe hypoglycemic episode occurred . WHO-DTSQ scores increased significantly more in group A ( from 26.7 ± 4.4 to 30.3 ± 4.5 ) than in group B ( from 27.5 ± 4.8 to 28.6 ± 5.1 ) ( P = 0.04 ) . Role Physical , General Health , Vitality , and Role Emotional SF-36 scores improved significantly more in group A than in group B. CONCLUSIONS DID is at least as effective as traditional carbohydrate counting education , allowing dietary freedom for a larger proportion of type 1 diabetic patients . DID is safe , requires less time for education , and is associated with lower weight gain . DID significantly improved treatment satisfaction and several quality -of-life dimensions ", "Existing st and ards of the management of the diabetic patients are not efficient enough , and further improvement is needed . The major objective of this paper is to present and discuss the therapeutic effectiveness of an intensive care telematic system design ed and applied for intensive treatment of pregnant type 1 diabetic women . The developed system operates automatically , every night transferring all the data recorded during the day in the patient 's glucometer memory to a central clinical unit . In order to assess the efficiency of the design ed and developed system , a 3-year r and omized prospect i ve clinical trial was conducted , using the study group and the control group , each consisting of 15 pregnant type 1 diabetic women . All patients were treated by the same diabetologist . In the presented analysis , two indices calculated weekly were used for the assessment of glycemic control : MBG represents mean blood glucose level , and the universal J-index is sensitive to the glycemic level and glycemic variations . The most important results from the study concern : ( a ) better glycemic control in the study group in comparison with the control group during the course of treatment , as assessed by the average differences of the MBG and J indices calculated weekly ( n = 24 ) ( deltaMBG = -3.2 + /- 4.3 mg/dL , p = 0.0016 , deltaJ = -1.4 + /- 2.3 , p = 0.0065 ) ; ( b ) much more similar results in glycemic control among members of the study group compared to each other , than among members of the control group compared to each other , as indicated by significantly lower variations of the applied glycemic control indices ( SDMBG : 11.9 vs. 18.7 mg/dL , p = 0.0498 ; SDJ : 6.5 vs. 10.9 , p = 0.0318 ) ; ( c ) the observed tendency of a better glycemic control for patients with a lower level of intelligence ( IQ 0.05 ) . This telematic intensive care system improved the effectiveness of diabetes treatment during pregnancy . It also allows the diabetologist 's strategy to be much more precise than if it were conducted without telematic support . This telematic system is inexpensive and simple in use", "OBJECTIVE To assess the effect of an Internet-based glucose monitoring system ( IBGMS ) on A1C levels in patients with type 2 diabetes treated with insulin . RESEARCH DESIGN AND METHODS This trial involved 50 patients r and omly assigned to receive either conventional treatment alone or with additional follow-up through an IBGMS for 6 months . Patients r and omized to the intervention group uploaded blood glucose readings every 2 weeks to a secure Web site for review and receipt of feedback from their endocrinologist . A1C and laboratory test results were collected at 0 , 3 , and 6 months . RESULTS The baseline parameters were not significantly different . Over a 6-month follow-up , A1C dropped from 8.8 to 7.6 % ( P IBGMS significantly improved A1C levels in patients with type 2 diabetes treated with insulin", "This study was performed to evaluate the effects of a patient-centered , tablet computer-based self-monitoring system for chronic disease care . A 3-month r and omized controlled pilot trial was conducted to compare the use of a computer-based self-monitoring system in disease self-care ( intervention group ; n = 33 ) with a conventional self-monitoring method ( control group ; n = 30 ) in patients with type 2 diabetes mellitus and /or hypertension . The system was equipped with a 2-in-1 blood glucose and blood pressure monitor , a reminder feature , and video-based educational material s for the care of the two chronic diseases . The control patients were given only the 2-in-1 monitor for self-monitoring . The outcomes reported here included the glycated hemoglobin ( HbA1c ) level , fasting blood glucose level , systolic blood pressure , diastolic blood pressure , chronic disease knowledge , and frequency of self-monitoring . The data were collected at baseline and at 1- , 2- , and 3-month follow-up visits . The patients in the intervention group had a significant decrease in mean systolic blood pressure from baseline to 1 month ( p mean diastolic blood pressure were seen in the intervention group compared with the control group after 1 month ( p fasting blood glucose level , the HbA1c level , or chronic disease knowledge . The frequency of self-monitoring of blood glucose level and blood pressure was similar in both groups . The performances of the tablet computer-assisted and conventional disease self-monitoring appear to be useful to support/maintain blood pressure and diabetes control . The beneficial effects of the use of electronic self-care re sources and support provided via mobile technologies require further confirmation in longer-term , larger trials", "OBJECTIVE The Internet is used worldwide as a communication tool . To improve the quality of diabetes control , we investigated the effectiveness of an Internet-based blood glucose monitoring system ( IBGMS ) on controlling the changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS We conducted a r and omized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary 's Hospital for 3 months . The study subjects were treated with IBGMS for 12 weeks , and the control group received the usual outpatient management over the same period . HbA(1c ) and other laboratory tests were performed twice , once at the beginning of the study and again at the end of the study . RESULTS The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age , sex , diabetes duration , BMI , blood pressure , HbA(1c ) , and other laboratory data . On follow-up examination 12 weeks later , HbA(1c ) levels were significantly decreased from 7.59 to 6.94 % within the intervention group ( P HbA(1c ) levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA(1c ) ( 6.94 vs. 7.62 % ; P HbA(1c ) lower HbA(1c ) than those in the control group ( 6.38 vs. 6.99 % ; P HbA(1c ) > or = 7.0 % , the difference between the two groups appeared more obvious : HbA(1c ) levels at the end of the study were 8.12 % . CONCLUSIONS This new IBGMS result ed in a significant reduction of HbA(1c ) during the study period . We propose that this IBGMS be used as a method for improving diabetes control", "OBJECTIVE We compared the short-term efficacy of home telemonitoring coupled with active medication management by a nurse practitioner with a monthly care coordination telephone call on glycemic control in veterans with type 2 diabetes and entry A1C ≥7.5 % . RESEARCH DESIGN AND METHODS Veterans who received primary care at the VA Pittsburgh Healthcare System from June 2004 to December 2005 , who were taking oral hypoglycemic agents and /or insulin for ≥1 year , and who had A1C ≥7.5 % at enrollment were r and omly assigned to either active care management with home telemonitoring ( ACM+HT group , n = 73 ) or a monthly care coordination telephone call ( CC group , n = 77 ) . Both groups received monthly calls for diabetes education and self-management review . ACM+HT group participants transmitted blood glucose , blood pressure , and weight to a nurse practitioner using the Viterion 100 TeleHealth Monitor ; the nurse practitioner adjusted medications for glucose , blood pressure , and lipid control based on established American Diabetes Association targets . Measures were obtained at baseline , 3-month , and 6-month visits . RESULTS Baseline characteristics were similar in both groups , with mean A1C of 9.4 % ( CC group ) and 9.6 % ( ACM+HT group ) . Compared with the CC group , the ACM+HT group demonstrated significantly larger decreases in A1C at 3 months ( 1.7 vs. 0.7 % ) and 6 months ( 1.7 vs. 0.8 % ; P ACM+HT group demonstrated significantly greater reductions in A1C by 3 and 6 months . However , both interventions improved glycemic control in primary care patients with previously inadequate control", "OBJECTIVE To report results from YourWay , an Internet-based self-management intervention for adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS A total of 72 adolescents with type 1 diabetes , ages 13–17 years , were r and omized to a usual-care-plus-Internet support or a usual-care group . The intervention was design ed to enhance problem-solving barriers to self-management . A1C was obtained from medical records , and problem-solving and self-management were obtained via adolescent report . RESULTS Group differences were not statistically significant using intent-to-treat analyses . Using as-treated analyses , adolescents in the treatment condition showed statistically significant improvement in self-management ( d = 0.64 ; P = 0.02 ) and important improvements in problem-solving ( d = 0.30 ; P = 0.23 ) and A1C ( d = −0.28 ; P = 0.27 ) . Mean A1C for the intervention group remained constant ( −0.01 % ) , while the control group increased ( 0.33 % ) . CONCLUSIONS This brief trial suggests that self-management support delivered through a secure website may improve self-management and offset typical decreases in adolescent glycemic control ", " This article describes the design and implementation of an online diabetes self-management intervention for a sample of inner-city African Americans with diabetes . Study participants were r and omly assigned to the treatment ( 26 ) and control ( 21 ) conditions . The results indicate that treatment group participants were more likely to achieve positive outcomes in terms of lowered hemoglobin A1c and body mass index measurements than were control group members . These findings support the development of telehealth interventions to promote effective chronic disease management in medically underserved communities", "CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care . OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older , ethnically diverse , medically underserved patients with diabetes . DESIGN , Setting , and Patients A r and omized controlled trial was conducted , comparing telemedicine case management to usual care , with blinded outcome evaluation , in 1,665 Medicare recipients with diabetes , aged > /= 55 years , residing in federally design ated medically underserved areas of New York State . Interventions Home telemedicine unit with nurse case management versus usual care . Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c ( HgbA1c ) , low density lipoprotein ( LDL ) cholesterol , and blood pressure levels . RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints ( HgbA1c , p = 0.001 ; LDL , p systolic and diastolic blood pressure , p = 0.024 ; p HgbA1c , 3.84 ( -0.08 , 7.77 ) mg/dL for LDL cholesterol , and 4.32 ( 1.93 , 6.72 ) mm Hg for systolic and 2.64 ( 1.53 , 3.74 ) mm Hg for diastolic blood pressure . There were 176 deaths in the intervention group and 169 in the usual care group ( hazard ratio 1.01 [ 0.82 , 1.24 ] ) . CONCLUSIONS Telemedicine case management result ed in net improvements in HgbA1c , LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries . Mortality was not different between the groups , although power was limited . Trial Registration http:// clinical trials.gov Identifier : NCT00271739", "Background Diabetes self-care by patients has been shown to assist in the reduction of disease severity and associated medical costs . We compared the effectiveness of two different diabetes self-care interventions on glycemic control in a racially/ethnically diverse population . We also explored whether reductions in glycated hemoglobin ( HbA1c ) will be more marked in minority persons . Methods We conducted an open-label r and omized controlled trial of 376 patients with type 2 diabetes aged ≥18 years and whose last measured HbA1c was ≥7.5 % ( ≥58 mmol/mol ) . Participants were r and omized to : 1 ) a Chronic Disease Self-Management Program ( CDSMP ; n = 101 ) ; 2 ) a diabetes self-care software on a personal digital assistant ( PDA ; n = 81 ) ; 3 ) a combination of interventions ( CDSMP + PDA ; n = 99 ) ; or 4 ) usual care ( control ; n = 95 ) . Enrollment occurred January 2009-June 2011 at seven regional clinics of a university-affiliated multi-specialty group practice . The primary outcome was change in HbA1c from r and omization to 12 months . Data were analyzed using a multilevel statistical model . Results Average baseline HbA1c in the CDSMP , PDA , CDSMP + PDA , and control arms were 9.4 % , 9.3 % , 9.2 % , and 9.2 % , respectively . HbA1c reductions at 12 months for the groups averaged 1.1 % , 0.7 % , 1.1 % , and 0.7 % , respectively and did not differ significantly from baseline based on the model ( P = .771 ) . Besides the participants in the PDA group reporting eating more high-fat foods compared to their counterparts ( P in HbA1c for minority persons but rather modest reductions for all racial/ethnic groups . Conclusions Although behavioral and technological interventions can result in some modest improvements in glycemic control , these interventions did not fare significantly better than usual care in achieving glycemic control . More research is needed to underst and how these interventions can be most effective in clinical practice . The reduction in HbA1c levels found in our control group that received usual care also suggests that good routine care in an integrated healthcare system can lead to better glycemic control . Trial registration Clinical trials.gov Identifier : NCT01221090", "Background Persistently poor glycemic control in adult type 1 diabetes patients is a common , complex , and serious problem initiating significant damage to the cardiovascular , renal , neural , and visual systems . Currently , there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores . Objective The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text-message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group r and omized controlled trial . Methods Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia . In a 6-month intervention , followed by a three-month follow-up , patients ( n=72 ) were r and omized to usual care ( control group ) or usual care and the use of a smartphone application ( Glucose Buddy ) with weekly text-message feedback from a Certified Diabetes Educator ( intervention group ) . All outcome measures were collected at baseline and every three months over the study period . Patients ’ glycosylated hemoglobin levels ( HbA1c ) were measured with a blood test and diabetes-related self-efficacy , self-care activities , and quality of life were measured with online question naires . Results The mean age of patients was 35.20 years ( SD 10.43 ) ( 28 male , 44 female ) , 39 % ( 28/72 ) were male , and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years ( SD 9.66 ) . Of the initial 72 patients , 53 completed the study ( 25 intervention , 28 control group ) . The intervention group significantly improved glycemic control ( HbA1c ) from baseline ( mean 9.08 % , SD 1.18 ) to 9-month follow-up ( mean 7.80 % , SD 0.75 ) , compared to the control group ( baseline : mean 8.47 % , SD 0.86 , follow-up : mean 8.58 % , SD 1.16 ) . No significant change over time was found in either group in relation to self-efficacy , self-care activities , and quality of life . Conclusions In adjunct to usual care , the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12612000132842 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12612000132842 ( Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u )", "Objective — To evaluate Diabeto , a computer-assisted diet education system . Research Design And Methods — One hundred five patients with insulin-dependent diabetes mellitus ( IDDM ) or non-insulin-dependent diabetes mellitus ( NIDDM ) were divided into two r and omized groups to participate in the evaluation of Diabeto . With free access through Minitel , the French public videotex network , Diabeto helps diabetic patients self-monitor their diets and balance their meals with personalized counseling . Results — During the first 6-mo study , group A ( 54 patients ) used Diabeto , whereas group B ( 51 patients ) were control subjects . For the second 6-mo study , group B used the system . Evaluation was based on patients ' dietetic knowledge , dietary habits , and metabolic balance . Conclusions –Diabeto led to a significant improvement of dietetic , knowledge in group A ( P improved dietary habits ; decreased caloric intake in patients initially overeating ( P of dietary carbohydrate from 39.7 ± 0.7 to 42.9 ± 0.9 % in patients with an initial intake decrease of fat intake from 41.9 ± 0.9 to 37.4 ± 1.1 % in patients with an initial intake of > 35 % fat ( P < 0.0005 ) . In the second study , in addition to similar improvements to those observed in the first study , HbA1 decreased from 11.0 ± 0.4 to 9.9 ± 0.4 % ( P < 0.005 ) and fructosamine from 5.00 ± 0.17 to 4.57 ± 0.17 % ( P < 0.001 ) . Diabeto appears to be an effective therapeutic tool in the control of metabolic diseases", "OBJECTIVE Investigate the effectiveness of an educational intervention that used both the cellular phone with a short messaging service ( SMS ) and the Internet on the glycemic control of the patients with type 2 diabetes mellitus . METHODS Twenty-five patients were r and omly assigned to an intervention group and twenty-six to a control group . The intervention was applied for 12 months . The goal of the intervention was to keep blood glucose concentrations close to the normal range ( HbA(1)c access a website by using a cellular phone or to wiring the Internet and input their blood glucose levels weekly . Participants were sent the optimal recommendations by both cellular phone and the Internet weekly . RESULTS Participants in the intervention group had lower HbA(1)c over 12 months when compared with the control group . At 12 months the change from baseline in HbA(1)c was -1.32 in the intervention group versus + 0.81 in the control group . Two hours post-meal glucose ( 2HPMG ) had a significantly greater decline in the intervention group after 12 months when compared with the control group ( -100.0 versus + 18.1mg/dl ) . CONCLUSION This educational intervention using the Internet and a SMS by cellular phone rapidly improved and stably maintained the glycemic control of the patients with type 2 diabetes mellitus", "This study evaluated the 12-month follow-up results and costs of a personalized , medical office-based intervention focused on behavioral issues related to dietary self-management . Two hundred and six adults having diabetes attending an internal medicine outpatient clinic visit were r and omized to either Usual Care or to Brief Intervention . The single session intervention involved touchscreen computer-assisted assessment that provided immediate feedback on key barriers to dietary self-management , goal setting and problem-solving counselling . Follow-up components included phone calls and videotape intervention relevant to each participant . Brief Intervention produced significantly greater improvement than Usual Care on multiple measures of change in dietary behaviour ( e.g. , covariate adjusted difference of 2.2 % of calories from fat ; p = 0.023 ) and on serum cholesterol levels ( covariate adjusted difference of 15 mg/dl ; p = 0.002 ) at 12-month follow-up . There were also significant differences favouring intervention on patient satisfaction ( p HbA1c levels . The costs of intervention ( $ 137 per patient ) were modest relative to many commonly used practice", "OBJECTIVE —To investigate the long-term effectiveness of the Internet-based glucose monitoring system ( IBGMS ) on glucose control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a prospect i ve , r and omized , controlled trial in 80 patients with type 2 diabetes for 30 months . The intervention group was treated with the IBGMS , while the control group made conventional office visits only . HbA1c ( A1C ) was performed at 3-month intervals . For measuring of the stability of glucose control , the SD value of A1C levels for each subject was used as the A1C fluctuation index ( HFI ) . RESULTS —The mean A1C and HFI were significantly lower in the intervention group ( n = 40 ) than in the control group ( n = 40 ) . ( A1C [ mean ± SD ] 6.9 ± 0.9 vs. 7.5 ± 1.0 % , P = 0.009 ; HFI 0.47 ± 0.23 vs. 0.78 ± 0.51 , P = 0.001 ; intervention versus control groups , respectively ) . Patients in the intervention group with a basal A1C ≥7 % ( n = 27 ) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study ( P = 0.022 ) . Control patients with a basal A1C distribution of A1C levels , whereas the A1C levels in the intervention group remained stable throughout the study with low HFI . CONCLUSIONS —Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability ", "This study aim ed to test the effects of providing Web-based diabetes education to individuals with type 2 diabetes on the A1c level and health check attendance . The study participants comprised 122 individuals with type 2 diabetes , who had access to the Internet , had completed their basic diabetes education , and had similar basic situational factors . Using a r and omization method , these participants were chosen from the patients being monitored by the diabetes nurses . The experimental group ( n = 61 ) was monitored via the Web . From measurements recorded in the sixth month of monitoring , we found that A1c levels of the individuals with diabetes who were monitored through the Web decreased ( t = 6.63 ; P and the rate of attending health check visits increased ( z = 5.97 ; P < .05 ) , while no difference was detected in the control group ( t = −0.63 ; P = .534 ; z = −0.80 ; P = .426 ) . To maintain glycemic control , Web use could be adopted as a complementary tool for monitoring individuals with diabetes", "Aims In 2011 , we demonstrated that an individualized health management system employing advanced medical information technology , design ated ubiquitous (u)-healthcare , was helpful in achieving glycemic control without hypoglycemia in patients with diabetes . Following this , we generated a new multidisciplinary u-healthcare system by upgrading our clinical decision support system ( CDSS ) rule engine and integrating a physical activity-monitoring device and dietary feedback into a comprehensive package . Methods In a r and omized , controlled clinical trial , patients with type 2 diabetes aged over 60 years were assigned r and omly to a self-monitored blood glucose ( SMBG ) group ( N = 50 ) or u-healthcare group ( N = 50 ) for 6 months . The primary endpoint was the proportion of patients achieving glycated hemoglobin ( HbA1c ) were also investigated . The u-healthcare group was educated to use a specially design ed glucometer and an activity monitor that automatically transferred test results to a hospital-based server . An automated CDSS rule engine generated and sent patient-specific messages about glucose , diet , and physical activity to their mobile phones and a Web site . Results After 6 months of follow-up , the HbA1c level was significantly decreased in the u-healthcare group [ 8.0 ± 0.7 % ( 64.2 ± 8.8 mmol/mol ) to 7.3 ± 0.9 % ( 56.7 ± 9.9 mmol/mol ) ] compared with the SMBG group [ 8.1 ± 0.8 % ( 64.9 ± 9.1 mmol/mol ) to 7.9 ± 1.2 % ( 63.2 ± 12.3 mmol/mol ) ] ( P . The proportion of patients with HbA1c was greater in the u-healthcare group ( 26 % ) than in the SMBG group ( 12 % ; P decreased and lipid profiles improved in the u-healthcare group but not in the SMBG group . Conclusion This u-healthcare service provided effective management for older patients with type 2 diabetes ( Clinical Trial . Gov : NCT01137058 )", "Objective : There is a need for practical , efficient and broad-reaching diabetes self-management interventions that can produce changes in lifestyle behaviours such as healthy eating and weight loss . The objective of this study was to evaluate such a computer-assisted intervention . Methods : Type 2 diabetes primary care patients ( n=335 ) from fee-for-service and health maintenance organization setting s were r and omized to social cognitive theory-based tailored self-management ( TSM ) or computer-aided enhanced usual care ( UC ) . Intervention consisted of computer-assisted self-management assessment and feedback , tailored goal - setting , barrier identification , and problem-solving , followed by health counsellor interaction and follow-up calls . Outcomes were changes in dietary behaviours ( fat and fruit/vegetable intake ) , haemoglobin A1c ( HbA1c ) , lipids , weight , quality of life , and depression . Results : TSM patients reduced dietary fat intake and weight significantly more than UC patients at the 2-month follow-up . Among patients having elevated levels of HbA1c , lipids or depression at baseline , there were consistent directional trends favouring intervention , but these differences did not reach significance . The intervention proved feasible and was implemented successfully by a variety of staff . Conclusions : This relatively low-intensity intervention appealed to a large , generally representative sample of patients , was well implemented , and produced improvement in targeted behaviours . Implication s of this practical clinical trial for dissemination are discussed", "Background : Diabetes mellitus is a complex disease with serious complications . Electronic decision support , providing information that is shared and discussed by both patient and physician , encourages timely interventions and may improve the management of this chronic disease . However , it has rarely been tested in community-based primary care . Methods : In this pragmatic r and omized trial , we r and omly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care . The intervention involved shared access by the primary care provider and the patient to a Web-based , colour-coded diabetes tracker , which provided sequential monitoring values for 13 diabetes risk factors , their respective targets and brief , prioritized messages of advice . The primary outcome measure was a process composite score . Secondary outcomes included clinical composite scores , quality of life , continuity of care and usability . The outcome assessors were blinded to each patient ’s intervention status . Results : We recruited sequentially 46 primary care providers and then 511 of their patients ( mean age 60.7 [ st and ard deviation 12.5 ] years ) . Mean follow-up was 5.9 months . The process composite score was significantly better for patients in the intervention group than for control patients ( difference 1.27 , 95 % confidence interval [ CI ] 0.79–1.75 , p clinical composite score also had significantly more variables with improvement for the intervention group ( 0.59 , 95 % CI 0.09–1.10 , p = 0.02 ) , including significantly greater declines in blood pressure ( −3.95 mm Hg systolic and −2.38 mm Hg diastolic ) and glycated hemoglobin ( −0.2 % ) . Patients in the intervention group reported greater satisfaction with their diabetes care . Interpretation : A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care . ( Clinical Trials.gov trial register no. NCT00813085 .", "The purpose of this study was to evaluate the effrcacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin- dependent diabetes . Metabolic control , patients ' psychosocial status , family functioning , perceived quality of life , patterns of parental/child responsibility for daily diabetes maintenance , and nursing time-on-task were evaluated . One hundred six pediatric patients ( mean age= 13.3 years ) were r and omly assigned to an experimental or control outpatient clinic for 1 year . Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks . Transmitted data were review ed by nurse practitioners who telephoned subjects to discuss regimen adjustments . Control subjects received st and ard care with regimen adjustments made by physicians . There were no significant between-group differences for metabolic control , rates of hospitalization or emergency-room visits , psychological status , general family functioning , quality of life , or parent-child responsibility . A significant decrease was noted in nursing time-on-task for experimental subjects", "We conducted a six-month prospect i ve interventional crossover study examining a computerized diabetes monitoring system ( DMS ) that conveyed dietary information . The objectives were to compare glycaemic control between intervention and control periods , and to assess patients ' acceptance of the DMS . Nineteen patients were r and omized into two groups , each using the DMS for three months and serving as the control group for another three months . The patients recorded information about their meal portions and blood glucose readings in a h and -held electronic diary . After transmitting the data to the DMS through a telephone modem , the patients received immediate feedback about the carbohydrate , protein and fat content of the meal , as well as the calorie content . A significant improvement in glycaemic control was achieved during intervention compared with control periods ( mean HbA1C reduction of 0.825 % ) . The DMS was also highly acceptable : 95 % patients found it easy to operate while 63 % found it useful . The DMS was thus a feasible model of telemedicine in diabetes care and a larger study is warranted to examine its cost-effectiveness", "BACKGROUND The emergence of the World Wide Web in the last decade has made it feasible for the Internet to be a vehicle for chronic disease management . METHODS A r and omized controlled trial ( n = 62 ) testing the effects of a 6-month web-based intervention plus usual care , compared with usual care alone , among adults 60 years of age and older with diabetes . The outcomes were hemoglobin A1c ( HbA1c ) , blood pressure , weight , cholesterol , and high-density lipoprotein ( HDL ) levels . RESULTS A multivariate analysis of covariance controlling for all baseline outcome variables , age , gender , and number of years with diabetes showed significant ( P = 0.001 ) reductions in HbA1c , weight , and cholesterol level and significant improvement in HDL levels in the intervention versus the control group . CONCLUSIONS Findings show a web-based intervention was effective in improving HbA1c , weight , cholesterol , and HDL levels at a 6-month follow-up . Future research is needed to investigate the long-term effectiveness of web-based interventions", "PURPOSE The present study evaluated whether an intervention using the SMS by personal cellular phone and internet would improve the levels of plasma glucose of obese type 2 diabetes at 3 , 6 , 9 , and 12 months . METHODS This is a quasi-experimental design with pre- and follow-up tests . Participants were recruited from the endocrinology outpatient department of tertiary care hospital located in an urban city of South Korea . Eighteen patients were r and omly assigned to an intervention group and 16 to a control group . The goal of the intervention was to decrease body weight and keep blood glucose concentrations close to the normal range . Patients were requested to record their blood glucose level in a weekly diary on the website by personal cellular phones or computer internet . The research er sent optimal recommendations to each patient , by both the cellular phone and the Internet weekly . The intervention was applied for 1 year . RESULTS Glycosylated hemoglobin ( HbA(1)c ) decreased 1.22 percentage points at 3 months , 1.09 percentage points at 6 months , 1.47 percentage points at 9 months , and 1.49 percentage points at 12 months compared with baseline in the intervention group ( all time points , p 2-h post-pr and ial test ( 2HPPT ) of 120.1mg/dl at 3 months , 58.9 mg/dl at 6 months , 62.0mg/dl at 9 months , and 102.9 mg/dl at 12 months compared with baseline ( all time points , p web-based intervention using SMS of personal cellular phone and Internet improved HbA(1)c and 2HPPT at 3 , 6 , 9 , and 12 months in patients with obese type 2 diabetes", "OBJECTIVE To determine whether a system of telemedicine support can improve glycemic control in type 1 diabetes . RESEARCH DESIGN AND METHODS A 9-month r and omized trial compared glucose self-monitoring real-time result transmission and feedback of results for the previous 24 h in the control group with real-time graphical phone-based feedback for the previous 2 weeks together with nurse-initiated support using a web-based graphical analysis of glucose self-monitoring results in the intervention group . All patients aged 18 - 30 years with HbA(1c ) ( A1C ) levels of 8 - 11 % were eligible for inclusion . RESULTS A total of 93 patients ( 55 men ) with mean diabetes duration ( means + /- SD ) 12.1 + /- 6.7 years were recruited from a young adult clinic . In total , the intervention and control groups transmitted 29,765 and 21,400 results , respectively . The corresponding median blood glucose levels were 8.9 mmol/l ( interquartile range 5.4 - 13.5 ) and 10.3 mmol/l ( 6.5 - 14.4 ) ( P reduction in A1C in the intervention group after 9 months from 9.2 + /- 1.1 to 8.6 + /- 1.4 % ( difference 0.6 % [ 95 % CI 0.3 - 1.0 ] ) and a reduction in A1C in the control group from 9.3 + /- 1.5 to 8.9 + /- 1.4 % ( difference 0.4 % [ 0.03 - 0.7 ] ) . This difference in change in A1C between groups was not statistically significant ( 0.2 % [ -0.2 to 0.7 , P = 0.3 ) . CONCLUSIONS Real-time telemedicine transmission and feedback of information about blood glucose results with nurse support is feasible and acceptable to patients , but to significantly improve glycemic control , access to real-time decision support for medication dosing and changes in diet and exercise may be required", "AIMS The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide . To improve the quality and efficiency of chronic disease care , we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care ( UCDC ) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension . METHODS We conducted a r and omized , controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre . RESULTS After 12 weeks , there were significant improvements in HbA(1c ) in the intervention group ( 7.6 + /- 0.9 % to 7.1 + /- 0.8 % , P systolic and diastolic blood pressure , as well as improvements in total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels in the intervention group . Furthermore , there was a significant increase in adiponectin levels in the intervention group compared with the control group , although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group . CONCLUSIONS The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension", "Objective To improve the analysis of self-monitoring of blood glucose ( SMBG ) and its communication between patients and physicians by a telematic transmission of computerized SMBG and to study the consequences of its use on glucose control of insulin-dependent diabetic ( IDDM ) patients . Research Design and Methods A prospect i ve r and omized crossover trial with two 3-mo periods , one with SMBG recorded on traditional booklets ( booklet period ) and another with computerized SMBG transmitted to a central data base through a telematic network ( telematic period ) , comprised the study . During the latter phase , patients could receive computerized SMBG analysis on individual terminals connected to the telephone network ( Minitel system ) . Blood glucose recordings and HbA1c were measured at inclusion and end of each period . Eleven pairs of IDDM patients on intensified insulin therapy were r and omized within each pair to start with the telematic period ( group A ) or the booklet period ( group B ) . Results Telematic transmissions were successful ( initial HbA1c was low ( 6.7 % ) , it declined during the telematic period ( Δ = -0.41 % ) compared with the booklet period ( Δ = + 0.37 % , P = 0.05 ) . The percentage of low ( correlated with HbA1c changes during the telematic period ( r = 0.714 , P= 0.0014 ) but not the booklet period . The patients favored the telematic tool to analyze SMBG . Conclusions Telematic transmission of SMBG is feasible . It can improve SMBG analysis and perhaps glucose control , therefore offering a new way of communication between diabetic patients and their physicians", "OBJECTIVE To determine the effect of mobile phone intervention on HbA1c in type-2 Diabetes Mellitus ( DM ) patients living in rural areas of Pakistan . STUDY DESIGN R and omized controlled trial . PLACE AND DURATION OF STUDY Department of Endocrinology , Liaquat National Hospital , Karachi , from December 2013 to June 2014 . METHODOLOGY A total of 440 patients in intervention and control groups were enrolled . All patients between 18 - 70 years of age , residing in rural areas of Pakistan , HbA1c ³ 8.0 % and having personal functional mobile phone were included . The intervention group patients were called directly on mobile phone after every 15 days for a period of 4 months . They were asked about the self-monitoring blood glucose , intake of medications , physical activity , healthy eating and were physically examined after 4 months . However , the control group was examined initially and after 4 months physically in the clinic and there were no mobile phone contacts with these patients . RESULTS Patients in intervention group showed improvement ( p 0.001 ) in following diet plan from 17.3 % at baseline to 43.6 % at endline , however , the control group showed insignificant increase ( p=0.522 ) from 13.6 % at baseline to 15.9 % at endline . Intervention group ( RR = 2.71 , 95 % CI = 1.18 - 6.40 ) showed significant positive association with normalization of HbA1c levels . The relationship was adjusted for age , gender , socio-economic status , ethnicity , education , hypertension , medication , BMI , diet , LDL levels and physical activity . Dietary restriction and low LDL levels also showed significant associations with reduced HbA1c levels on multivariate analysis . CONCLUSION Mobile phone technology in rural areas of Pakistan was helpful in lowering HbA1c levels in intervention group through direct communication with the diabetic patients . Lowering LDL and following diabetic diet plan can reduce HbA1c in these patients and help in preventing future complications", "Introduction In this paper , we evaluated the feasibility of a telemedical ( TM ) support program and its effect on glycemic control in adolescents with type 1 diabetes mellitus ( T1DM ) . Thirty-six adolescents ( m=20 , median age at the start of the study : 15.3 years ( range : 10.7–19.3 years ) , median age at diagnosis : 9.3 years ( 2.1–13.8 years ) , median duration of disease : 6.4 years ( 1.0–12.8 years ) , HbA1c>8 % , all on intensified insulin therapy ) were r and omized in a crossover trial over 6 months ( 3 months with TM , 3 months with conventional support and paper diary ( PD ) ) . During the TM phase , the patients sent their data ( date , time , blood glucose , carbohydrate intake , insulin dosage ) via mobile phone , at least daily , to our server and diabetologists sent back their advice via short message service ( SMS ) once a week . Results Glycemic control improved during the TM phase , while it deteriorated during the PD phase : TM-PD group HbA1c ( % , median ( range ) ) : 9.05 ( 8–11.3 ) ( at 0 months ) , 8.9 ( 6.9–11.3 ) ( at 3 months ) , and 9.2 ( 7.4–12.6 ) ( at 6 months ) , and PD-TM group : 8.9 ( 8.3–11.6 ) , 9.9 ( 8.1–11 ) , and 8.85 ( 7.3–11.7 ) ( p TM support program to be a good idea . Technical problems with General Packet Radio Service ( GPRS ) data transmission led to data loss and decreased patient satisfaction . Conclusion Our telemedical support program , VIE-DIAB , proved to be feasible in adolescents and helped to improve glycemic control", "Introduction The aim of this study was to improve the quality of diabetes control and evaluate the efficacy of an Internet-based integrated healthcare system for diabetes management and safety . Methods We conducted a large-scale , multi-centre , r and omized clinical trial involving 484 patients . Patients in the intervention group ( n = 244 ) were treated with the Internet-based system for six months , while the control group ( n = 240 ) received the usual outpatient management over the same period . HbA1c , blood chemistries , anthropometric parameters , and adverse events were assessed at the beginning of the study , after three months , and the end of the study . Results There were no initial significant differences between the groups with respect to demographics and clinical parameters . Upon six-month follow-up , HbA1c levels were significantly decreased from 7.86 ± 0.69 % to 7.55 ± 0.86 % within the intervention group ( p control group . Postpr and ial glucose reduction was predominant . A subgroup with baseline HbA1c higher than 8 % and good compliance achieved a reduction of HbA1c by 0.8 ± 1.05 % . Glucose control and waist circumference reduction were more effective in females and subjects older than 40 years of age . There were no adverse events associated with the intervention . Discussion This e-healthcare system was effective for glucose control and body composition improvement without associated adverse events in a multi-centre trial . This system may be effective in improving diabetes control in the general population", "OBJECTIVE To determine whether the use of an Internet-based blood glucose monitoring system could improve glycemic control in adolescents with type 1 diabetes mellitus ( T1DM ) . METHODS In a r and omized , controlled clinical trial , a total of 70 adolescent subjects with T1DM were recruited . Subjects r and omized to the intervention group ( n = 36 ) were instructed to su bmi t their blood glucose levels weekly by Internet to the diabetes care team during a period of 6 months . Subjects r and omized to the control group ( n = 34 ) did not su bmi t results but were under routine follow-up . RESULTS At baseline , patients were 15.1 ± 2.6 years of age with mean HbA1c of 8.3 ± 1.3 % . At the 6-month follow-up period , no by-group differences in change from baseline to end of treatment HbA1c levels were detected . In the intervention group , 12/36 did not su bmi t blood glucose levels and were classified as non-compliant . In a secondary exploratory analysis in which non-compliant patients were omitted , HbA1c values in the compliant intervention group declined from 8.5 ± 1.7 % at baseline to 8.2 ± 1.2 % at 6 months , while in the control group HbA1c values increased from 8.2 ± 1.1 to 8.4 ± 1.1 % , this difference did not reach statistical significance . CONCLUSIONS An Internet-based blood glucose monitoring system was not associated with improved glycemic control in adolescents with T1DM . Identification of a sub-group of compliant subjects who may improve metabolic control by using this tool is needed", "Background : Telehealth-supported clinical interventions may improve diabetes self-management . We explored the feasibility of stepwise self-titration of oral glucose-lowering medication guided by a mobile telephone-based telehealth platform for improving glycemic control in type 2 diabetes . Methods : We recruited 14 type 2 diabetes patients to a one-year feasibility study with 1:1 r and omization . Intervention group patients followed a stepwise treatment plan for titration of oral glucose-lowering medication with self-monitoring of glycemia using real-time graphical feedback on a mobile telephone and remote nurse monitoring using a Web-based tool . We carried out an interim analysis at 6 months . Results : We screened 3476 type 2 diabetes patients ; 94 % of the ineligible did not meet the eligibility criteria for hemoglobin A1c ( HbA1c ) or current treatment . Mean ( st and ard deviation ) patient age at baseline was 58 ( 11 ) years , HbA1c was 65 ( 12 ) mmol/mol ( 8.1 % [ 1.1 % ] ) , body mass index was 32.9 ( 6.4 ) kg/m2 , median [ interquartile range ( IQR ) ] diabetes duration was 2.6 ( 0.6 to 4.7 ) years , and 10 ( 71 % ) were men . The median ( IQR ) change in HbA1c from baseline to six months was −10 ( −21 to 3 ) mmol/mol ( −0.9 % [ -1.9 % to 0 % ] ) in the intervention group and −5 ( −13 to 6 ) mmol/mol ( −0.5 % [ -1.2 % to 0.6 % ] ) in the control group . Six out of seven intervention group patients and four out of seven control group patients changed their oral glucose-lowering medication ( p = .24 ) . Conclusions : Self-titration of oral glucose-lowering medication in type 2 diabetes with self-monitoring and remote monitoring of glycemia is feasible , and further studies using adapted recruitment strategies are required to evaluate whether it improves clinical outcomes ", "Background : This study examined whether mobile phone-based , one-way video messages about diabetes self-care improve hemoglobin A1c ( A1C ) and self-monitoring of blood glucose ( SMBG ) . Methods : This was a 1-year prospect i ve r and omized trial with two groups . The active intervention lasted 6 months . The study enrolled 65 people with A1C > 8.0 % who were established ( > 6 months ) patients in the endocrinology clinics of the Walter Reed Health Care System . Participants were r and omized to receive “ usual care ” or self-care video messages from their diabetes nurse practitioner . Video messages were sent daily to cell phones of study participants . Hemoglobin A1c and SMBG data were collected at 0 , 3 , 6 , 9 , and 12 months . Results : Participants who received the messages had a larger rate of decline in A1C than people who received usual care ( 0.2 % difference over 12 months , adjusting for covariates ; p = .002 and p = .004 for the interaction between time and group and for the quadratic effect of time by group , respectively ) . Hemoglobin A1c decline was greatest among participants who received video messages and viewed > 10 a month ( 0.6 % difference over 12 months , adjusting for covariates ; p Self-monitoring of blood glucose metrics were not related to the intervention . Conclusions : A one-way intervention using mobile phone-based video messages about diabetes self-care can improve A1C . Engagement with the technology is an important predictor of its success . This intervention is simple to implement and sustain", "AIM Conventional follow-up of type 1 diabetic patients treated with continuous subcutaneous insulin infusion ( CSII ) was compared with intensive coaching using the Web and the cellular phone network for retrospective data transmission and short message service ( SMS ) . METHODS Thirty poorly controlled patients ( HbA1c 7.5 - 10 % ) were enrolled in a bicenter , open-label , r and omized , 12-month , two-period , crossover study . After a 1-month run-in period , 15 patients were r and omly assigned to receive weekly medical support through SMS based upon weekly review of glucose values , while 15 patients continued to download self-monitored blood glucose ( SMBG ) values on a weekly basis without receiving SMS . After 6 months , patients crossed over to the alternate sequence for 6 additional months . Visits at the clinic were maintained every 3 months . RESULTS Patients with long-st and ing inadequately controlled diabetes ( 24 + /- 13 years ) were included . A non-significant trend to reduction in HbA(1c ) ( -0.25+/-0.94 % , P mean glucose values ( -9.2+/-25 mg/dl , P=0.06 ) during the 6-month SMS sequence was observed as compared with the no-SMS period . No safety issue ( hypoglycemia , glucose variability ) was reported . Adherence to SMBG was not affected by the trial . Quality of life analysis suggests a significant improvement in DQOL global score , as well as the DQOL satisfaction with life subscale , during the SMS sequence . CONCLUSIONS Long-term telemedical follow-up of insulin pump-treated patients using a cellular phone- , SMS- and Web-based platform is feasible , safe , does not alter quality of life and associated with a trend toward improved metabolic control", "The aim of this study is to assess the impact of the internet-based upload blood glucose monitoring and therapy management system ( Carelink ® ) in patients with type 1 diabetes . Diabetic patients treated with pump infusion for ≥3 months were prospect ively r and omized to use the CareLink ® with ( 4 months ) and without ( 4 months ) diabetes-team initiated contact ( n = 36 , intervention group ) or to continue st and ard care for 4 months and then transfer to the CareLink ® without diabetes-team initiated contact ( n = 34 , control group ) . In the first 4 months , treatment was adjusted monthly by the same team in both groups . Main outcome measures were HbA1c level and scores on the Diabetes Treatment Satisfaction and Diabetes Quality of Life Question naires . Patients who su bmi tted Mean patient age was 14.02 ± 5.33 years ; mean diabetes duration , 6.4 ± 4.7 years ; median duration of pump treatment , 2.5 years . After 4 months , mean HbA1c level decreased from 8.75 ± 0.84 to 8.45 ± 0.90 % in the intervention group ( p = 0.013 ) and from 8.65 ± 0.57 to 8.37 ± 0.73 % in the control group ( p = 0.054 ) . Within the intervention group , the difference in the change in HbA1c levels between compliant and noncompliant patients was significant ( 8.17 ± 0.81 vs. 8.99 ± 0.85 % , p = 0.017 ) . Only in the compliant subgroup was the decrease from baseline significant ( p = 0.006 ) . Similar findings were noted in the control group at 8 months ( p in question naire scores at 4 or 8 months in either group . Use of the CareLink ® system is associated with significantly improved glycemic control in compliant patients , with no apparent effect on patient satisfaction or quality of life ", "OBJECTIVE There is a well-documented gap between diabetes care guidelines and the services received by patients in most health care setting s. This report presents 12-month follow-up results from a computer-assisted , patient-centered intervention to improve the level of recommended services patients received from a variety of primary care setting s. RESEARCH DESIGN AND METHODS A total of 886 patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program . Physicians were stratified and r and omized to intervention or control conditions and evaluated on two primary outcomes : number of recommended laboratory screenings and recommended patient-centered care activities completed from the National Committee on Quality Assurance/American Diabetes Association Provider Recognition Program ( PRP ) . Secondary outcomes were evaluated using the Problem Areas in Diabetes 2 quality of life scale , lipid and HbA1c levels , and the Patient Health Question naire-9 depression scale . RESULTS The program was well implemented and significantly improved both the number of laboratory assays and patient-centered aspects of diabetes care patients received compared with those in the control condition . There was overall improvement on secondary outcomes of lipids , HbA1c , quality of life , and depression scores ; between-condition differences were not significant . CONCLUSIONS Staff in small , mixed-payer primary care offices can consistently implement a patient-centered intervention to improve PRP measures of quality of diabetes care . Alternative explanations for why these process improvements did not lead to improved outcomes , and suggested directions for future research are discussed", "AIMS The primary objective was to evaluate the impact of the smart phone-based diabetes management application , Welltang , on glycated hemoglobin ( HbA1c ) . The second objective was to measure whether Welltang improves blood glucose , low-density lipoprotein cholesterol , weight , blood pressure , hypoglycemic events , satisfaction of patients to use Welltang , diabetes knowledge of patients , and self-care behaviors . METHODS One hundred evenly r and omized subjects with diabetes , aged 18 - 74years , were recruited from the outpatient Department of Endocrinology for a 3-month study . The Welltang intervention group received training for the use of Welltang , while the control group received their usual st and ard of care . HbA1c , blood glucose , low-density lipoprotein cholesterol , weight , blood pressure , hypoglycemic events , satisfaction of patients to use Welltang , diabetes knowledge of patients , and self-care behaviors were measured . Patient data were analyzed using independent t test and paired sample test using SPSS version 12 . RESULTS The average decrease in HbA1c was 1.95 % ( 21mmol/mol ) in the intervention group and 0.79 % ( 8mmol/mol ) in the control group ( P self-monitored blood glucose , diabetes knowledge , and self-care behaviors improved in patients in the intervention group . Eighty four percent of patients in the intervention group were satisfied with the use of Welltang . Differences in hypoglycemic events , low-density lipoprotein cholesterol , weight , and blood pressure were not statistically significant . CONCLUSION Diabetes patients using the Welltang application achieved statistically significant improvements in HbA1c , blood glucose , satisfaction of patients to use of Welltang , diabetes knowledge , and self-care behaviors", "RATIONALE , AIMS AND OBJECTIVES Utilizing information technology , such as Internet and cellphones , holds great promise in enhancing diabetic care . Yet few studies have examined the impact of cellphone technology on type 2 diabetics ' self-care . The primary aim of the study is to examine the feasibility of utilizing this technology to assist with diabetes self-care in a clinic population as well as its impact on clinical outcomes . METHODS Thirty patients with a diagnosis of type 2 diabetes at two Community Health Centers were r and omized to intervention or control . Intervention patients participated in a brief intervention and received tailored daily messages via cellphone prompting them to enhance their diabetic self-care behaviour . Patients at the control site continued with their st and ard diabetes self-management . RESULTS A mean improvement in HbA1c levels was apparent ( -0.1 , SD = 0.3 % ; P = 0.1534 ) in the intervention group , compared with a mean deterioration in the control ( 0.3 , SD = 1.0 % ; P = 0.3813 ) , yet without statistical significance . Self-efficacy scores improved significantly in the intervention group ( -0.5 , SD = 0.6 ; P = 0.0080 ) compared with no improvement in the control ( 0.0 , SD = 1.0 ; P = 0.9060 ) . Participants encountered numerous technological barriers when attempting to adhere to the intervention protocol . CONCLUSION The results indicate the intervention had a positive impact on some clinical outcome and self-efficacy . Although the technology appears feasible in a clinical setting technology must be made more user-friendly before a larger phase II trial is conducted", "BACKGROUND Telemedicine-based diabetes management improves outcomes versus clinic care but is seldom implemented by healthcare systems . In order to advance telemedicine-based management as a practical option for veterans with persistent poorly controlled diabetes mellitus ( PPDM ) despite clinic-based care , we evaluated a comprehensive telemedicine intervention that we specifically design ed for delivery using existing Veterans Health Administration ( VHA ) clinical staffing and equipment . MATERIAL S AND METHODS We conducted a 6-month r and omized trial among 50 veterans with PPDM ; all maintained hemoglobin A1c ( HbA1c ) levels continuously > 9.0 % for > 1 year despite clinic-based management . Participants received usual care or a telemedicine intervention combining telemonitoring , medication management , self-management support , and depression management ; existing VHA clinical staff delivered the intervention . Using linear mixed models , we examined HbA1c , diabetes self-care ( measured by the Self-Care Inventory-Revised question naire ) , depression , and blood pressure . RESULTS At baseline , the model-estimated common HbA1c intercept was 10.5 % . By 6 months , estimated HbA1c had improved by 1.3 % for intervention participants and 0.3 % for usual care ( estimated difference , -1.0 % , 95 % confidence interval [ CI ] , -2.0 % , 0.0 % ; p = 0.050 ) . Intervention participants ' diabetes self-care ( estimated difference , 7.0 ; 95 % CI , 0.1 , 14.0 ; p = 0.047 ) , systolic blood pressure ( -7.7 mm Hg ; 95 % CI , -14.8 , -0.6 ; p = 0.035 ) , and diastolic blood pressure ( -5.6 mm Hg ; 95 % CI , -9.9 , -1.2 ; p = 0.013 ) were improved versus usual care by 6 months . Depressive symptoms were similar between groups . CONCLUSIONS A comprehensive telemedicine intervention improved outcomes among veterans with PPDM despite clinic-based care . Because we specifically design ed this intervention with scalability in mind , it may represent a practical , real-world strategy to reduce the burden of poor diabetes control among veterans", "Objective The objective of this research is to determine the effects of mobile telehealth ( MTH ) on glycosylated haemoglobin ( HbA1c ) and other clinical and patient-reported outcomes in insulin-requiring people with diabetes . Methods A nine-month r and omised , controlled trial compared st and ard care to st and ard care supplemented with MTH ( self-monitoring , mobile-phone data transmissions , graphical and nurse-initiated feedback , and educational calls ) . Clinical ( HbA1c , blood pressure , daily insulin dose , diabetes outpatient appointments ( DOAs ) ) and question naire data ( health-related quality of life , depression , anxiety ) were collected . Mean group changes over time were compared using hierarchical linear models and Mann-Whitney tests . Results Eighty-one participants with a baseline HbA1c of 8.98 % ± 1.82 were r and omised to the intervention ( n = 45 ) and st and ard care ( n = 36 ) . The Group by Time effect revealed MTH did not significantly influence HbA1c ( p = 0.228 ) , but p values were borderline significant for blood pressure ( p = 0.054 ) and mental-health related quality of life ( p = 0.057 ) . Examination of effect sizes and 95 % confidence intervals for mean group differences at nine months supported the existence of a protective effect of MTH on mental health-related quality of life as well as depression . None of the other measured outcomes were found to be affected by the MTH intervention . Conclusions Findings from this study must be interpreted with caution given the small sample size , but they do not support the widespread adoption of MTH to achieve clinical ly significant changes in HbA1c . MTH may , however , have positive effects on blood pressure and protective effects on some aspects of mental health ", "BACKGROUND Patients with insulin dependent diabetes require frequent advice if their metabolic control is not optimal . This study focuses on the fiscal and administrative aspects of telemanagement , which was used to establish a supervised autonomy of patients on intensified insulin therapy . METHODS A prospect i ve , r and omised trial with 43 patients on intensified insulin therapy was conducted . Travelling distance to the diabetes centre was 50 min one way ; all patients had undergone a diabetes education course with lessons in dose adaptation . Patients were r and omly assigned to telecare ( n=27 ) or conventional care ( n=16 ) . They used BG-meters with a storage capacity of 120 values ( Precision QID Abbott/Medisense ) and transmitted their data over a combined modem/interface via telephone line to the diabetes centre . Data were displayed and stored by a customised software ( Precision Link Plus , Abbott/Medisense ) . Advice for proper dose adjustment was given by telephone . RESULTS Average time needed for instruction in the telemedical system was 15 min . Data were transmitted every 1 - 3 weeks and a teleconsultation was performed by phone every 2 - 4 weeks , depending on the extent of specific problems . On average , personal visits in the control group were performed once a month . Physician 's time expenditure for telemanagement , compared to conventional advice was moderately higher ( 50 vs. 42 min per month ) . A substantial amount of time on the patients side could be saved through replacing personal communications by telephone contacts and data transmission reduction ( 96 vs. 163 min/month including data transmission time ) . Setting up an optimal telemanagement scenario , a cost analysis was carried out yielding savings of approximately 650 euro per year per patient . HbA(1c ) dropped significantly from 8.2 to 7.0 % after 8 months of observation , but there was no significant difference between the intervention and control groups . Major technical problems with the telematic system did not occur during the study . CONCLUSIONS Telemanagement of insulin-requiring diabetic patients is a cost and time saving procedure for the patients and results in metabolic control comparable to conventional outpatient management", "OBJECTIVE The purpose of the study was to evaluate the safety of a computer program used by the patient for the adjustment of insulin doses to achieve tight glycemic control in type 1 diabetic subjects on intensive insulin therapy . METHODS Ten type 1 diabetic patients participated in the study . Using the basal-bolus ( UL-Humalog ) insulin regimen , they were r and omized in a crossover design to 2 intensive treatment periods of 8 weeks each , one with and the other without the assistance of a computer program via the Internet . They measured their capillary blood glucose regularly , and the results were entered on a daily basis into their log-book or in the computer . During intensive treatment with the computer , the software would provide recommendation for insulin dose adjustment according to specific algorithms . When on intensive treatment without computer assistance , they would adjust their own insulin dose according to the same algorithms . RESULTS The study subjects followed 89 % of the recommendations made by the computer . With the computer , subjects made more insulin dose adjustments ( 98 versus 50 ) than without . Intensive treatments with and without computer assistance result ed in a similar improvement of pre-meal/post-pr and ial capillary blood glucose from 7.6 + /- 2.7/9.5 + /- 2.5 to 6.7 + /- 2.3/8.8 + /- 2.5 and 6.7 + /- 2.6/9.0 + /- 2.6 mmol/L , respectively . Glygated hemoglobin also improved from 7.7 + /- 0.9 % to 7.2 + /- 0.7 and 7.3 + /- 0.8 % , respectively . The incidence of minor hypoglycemia was similar under both intensive treatments ( 7.9 + /- 4.0 and 7.1 + /- 5.0/patient/28 days , respectively ) . Both treatments increased patient behavior while patient knowledge of their disease was improved only during computer assistance . There was no effect on quality of life . The study subjects greatly appreciated the software and wanted to continue using it . CONCLUSIONS The study demonstrated that the use of computer software by the patient to adjust insulin doses for intensive insulin therapy is feasible and is not associated with increased adverse events", "AIMS To evaluate the feasibility and effectiveness of a telemedicine system based on internet in the follow-up of patients with type 2 diabetes mellitus ( T2DM ) . METHODS A prospect i ve r and omized telemedicine study with two parallel groups was design ed . 114 patients diagnosed T2DM were r and omly divided into telemedicine group and traditional face-to-face visit group as control . 57 cases were included for each group . 108 patients completed the trial , in which 53 cases in telemedicine group and 55 cases in control group . Patients in telemedicine group were taught to use telemedicine software to upload their blood glucose and other metabolic information at home at least every 2 weeks , and the research ers gave proper advices according to patients ' key behaviors . The telemedicine interval is 3 months . RESULTS Compared to control group , telemedicine group exhibited better HbA1c and fasting blood glucose controlling ( P decreased hypoglycemia risk ( P = 0.044 ) , and contributed to levels of HbA1c less than 7 % which is the target of our study ( P = 0.049 ) . CONCLUSIONS Telemedicine system can provide a tighter glycemic control for the treatment of T2DM patients , especially in cases with difficulties to access to the medical centre", "BACKGROUND Aggressive management of blood glucose reduces future diabetes-related complications , but this is difficult to achieve . METHODS This r and omized , controlled study tested the effect of using a wireless two-way pager-based automated messaging system to improve diabetes control through facilitated self-management . The system sent health-related messages to patients , with automatic forwarding of urgent patient responses to the health care team . RESULTS Participants in both the experimental ( pager ) and the control groups experienced an average hemoglobin A1c decrease of 0.1 - 0.3 % . More patients in the pager group were normotensive , and more felt that their health care was better by the end of the study . A total of 79 % of participants enjoyed using the pager , and 68 % wanted to continue using the system . CONCLUSIONS Utilizing a wireless , automated messaging system in clinical practice is a feasible , low-cost , interactive way to facilitate diabetes self-management , which is acceptable to patients . While providing a convenient way for patients and providers to communicate , this system can support automated recording and ready retrieval of these real-time interactions", "BACKGROUND We design ed a system for diabetes patients treated with glargine , a long-acting insulin , to make an automatic adjustment of insulin dose based on glucose level data and to provide the patients with the needed insulin dose by using a short message service ( SMS ) . We also compared diabetes patients who used our system with patients who received the conventional titration scheme . METHODS Included were 100 type 2 diabetes patients whose blood glucose was suboptimally controlled on their previous antidiabetes treatment . Each participant was assigned to either the intervention or control group , each with 50 patients , using adaptive r and omization . We applied our system to the intervention group for 12 weeks , whereas the control group received a conventional titration scheme , seeking a target fasting blood glucose of 120 mg/dL. RESULTS The fasting and postpr and ial glucose levels of the intervention group declined earlier than those of the control group . Lastly , a greater ( P = 0.023 ) reduction in hemoglobin A(1C ) from baseline to the end point was observed in the intervention group ( from 9.8 + /- 1.3 % to 7.4 + /- 0.7 % ) than in the control group ( from 9.8 + /- 1.2 % to 7.8 + /- 0.8 % ) . The incidence of symptomatic , asymptomatic , and nocturnal hypoglycemia was similar in both groups . There was a small increase in body weight from baseline to the end point with both the intervention ( 2.4 + /- 3.0 kg ) and control ( 2.2 + /- 2.8 kg ) groups . CONCLUSIONS This study demonstrated that SMS based on our specialized Internet-supported system is an effective and safe approach to long-acting insulin dose adjustments in patients with type 2 diabetes", "Background : In the United States , Spanish-speaking patients with diabetes often receive inadequate dietary counseling . Providing language and culture-concordant dietary counseling on an ongoing basis is critical to diabetes self-care . Objective : To determine if automated telephone nutrition support ( ATNS ) counseling could help patients improve glycemic control by duplicating a successful pilot in Mexico in a Spanish-speaking population in Oakl and , California . Design : A prospect i ve r and omized open-label trial with blinded endpoint assessment ( PROBE ) was performed . Participants : The participants were seventy-five adult patients with diabetes receiving care at a federally qualified health center in Oakl and , California . Interventions : ATNS , a computerized system that dialed patients on their phones , prompted them in Spanish to enter ( via keypad ) portions consumed in the prior 24 hours of various cultural-specific dietary items , and then provided dietary feedback based on proportion of high versus low glycemic index foods consumed . The control group received the same ATNS phone calls 14 weeks after enrollment . Main Measures : The primary outcome was hemoglobin A1c % ( A1c ) 12 weeks following enrollment . Key Results : Participants had no significant improvement in A1c ( –0.3 % in the control arm , –0.1 % in the intervention arm , P = .41 for any difference ) or any secondary parameters . Conclusions : In our study , an ATNS system did not improve diabetes control in a Spanish-speaking population in Oakl and", "Quinn CC , Shardell MD , Terrin ML , Barr EA , Ballew SH , Gruber-Baldini AL . Cluster-r and omized trial of a mobile phone personalized behavioral intervention for blood glucose control . Diabetes Care 2011;34:1934–1942 In the article listed above , the values for the 9-month glycated hemoglobins are incorrect due to a programming error . The significance of the results and the discussion remained unchanged . The changes to Table 1 and to the text are detailed below", "BACKGROUND To determine whether a Web-based diabetes case management program based in an electronic medical record can improve glycemic control ( primary outcome ) and diabetes-specific self-efficacy ( secondary outcome ) in adults with type 1 diabetes , a pilot r and omized controlled trial was conducted . METHODS A 12-month r and omized trial tested a Web-based case management program in a diabetes specialty clinic . Patients 21 - 49 years old with type 1 diabetes receiving multiple daily injections with insulin glargine and rapid-acting analogs who had a recent A1C > 7.0 % were eligible for inclusion . Participants were r and omized to receive either ( 1 ) usual care plus the nurse-practitioner-aided Web-based case management program ( intervention ) or ( 2 ) usual clinic care alone ( control ) . We compared patients in the two study arms for changes in A1C and self-efficacy measured with the Diabetes Empowerment Scale . RESULTS A total of 77 patients were recruited from the diabetes clinic and enrolled in the trial . The mean baseline A1C among study participants was 8.0 % . We observed a nonsignificant decrease in average A1C ( -0.48 ; 95 % confidence interval -1.22 to 0.27 ; P = 0.160 ) in the intervention group compared to the usual care group . The intervention group had a significant increase in diabetes-related self-efficacy compared to usual care ( group difference of 0.30 ; 95 % confidence interval 0.01 to 0.59 ; P = 0.04 ) . CONCLUSIONS Use of a Web-based case management program was associated with a beneficial treatment effect on self-efficacy , but change in glycemic control did not reach statistical significance in this trial of patients with moderately poorly controlled type 1 diabetes . Larger studies may be necessary to further clarify the intervention 's impact on health outcomes", "BACKGROUND A major problem in the dissemination of most interventions found to be efficacious is that they are of limited or unknown generalizability . OBJECTIVE To document the \" robustness , \" or external validity , of a computer-assisted diabetes self-management program across different patient characteristics , healthcare setting s ( mixed payer vs health maintenance organization ) , intervention staff , and outcomes . STUDY DESIGN A r and omized controlled trial evaluating a computer-assisted behavior change program for adult patients with type 2 diabetes mellitus ( n = 217 ) vs a computerized health risk assessment . METHODS Outcomes were identified using the RE- AIM framework and included program adoption among physicians , reach across patient groups , implementation , and behavioral ( fat intake and physical activity ) and biological ( glycosylated hemoglobin and lipid levels ) effectiveness measures . RESULTS The program achieved 41 % patient participation , variable adoption across healthcare setting s ( 76 % of health maintenance organization physicians vs 18 % of non-health maintenance organization physicians participated ) , good implementation , and improvement in behavioral outcomes . There were few significant interactions between treatment condition and patient characteristics , type of healthcare setting , or interventionist experience on effectiveness measures . CONCLUSIONS Patients and physicians were willing to participate in a computer-assisted dietary and physical activity goal - setting intervention , although participation varied by healthcare setting . Interventionists from different background s successfully delivered the intervention , and the results appear robust across various patient and delivery characteristics", "ABSTRACT OBJECTIVE To compare physiological outcomes and satisfaction for followup care between an interactive diabetes internet program and Diabetes Education Centres . METHOD A r and omized , controlled trial with outcomes of glycosylated hemoglobin ( A1C ) , fasting blood glucose , total cholesterol , triglycerides ( TG ) , high-density lipoprotein cholesterol , lowdensity lipoprotein cholesterol and patient satisfaction . Enrollment was staggered , with individuals assessed at baseline , 3 , 6 and 12 months . RESULTS Fifty-seven participants completed the study ( 20 control , 37 internet ) . Physiological outcomes were not statistically different between the 2 groups . However , within-group comparisons demonstrated a significant improvement in the internet group 's A1C , TG and satisfaction levels from baseline to 3 and 6 months ( p the internet program in other applications for diabetes management is needed", "STUDY OBJECTIVE Increasingly , low-income inner-city patients with diabetes utilize emergency departments ( EDs ) for acute and chronic care . We seek to determine whether a scalable , low-cost , unidirectional , text message-based mobile health intervention ( TExT-MED ) improves clinical outcomes , increases healthy behaviors , and decreases ED utilization in a safety net population . METHODS We conducted an r and omized controlled trial of 128 adult patients with poorly controlled diabetes ( glycosylated hemoglobin [ Hb A1C ] level ≥8 % ) in an urban , public ED . The TExT-MED group received 2 daily text messages for 6 months in English or Spanish . The primary outcome was change in Hb A1C level . Secondary outcomes included changes in medication adherence , self-efficacy , performance of self-care tasks , quality of life , diabetes-specific knowledge , ED utilization , and patient satisfaction . RESULTS Hb A1C level decreased by 1.05 % in the TExT-MED group compared with 0.60 % in the controls ( Δ0.45 ; 95 % confidence interval [ CI ] -0.27 to 1.17 ) at 6 months . Secondary outcomes favored the TExT-MED group , with the most sizable change observed in self-reported medication adherence ( as measured by the Morisky Medication Adherence Scale , an 8-point vali date d scale with higher scores representing better adherence ) , which improved from 4.5 to 5.4 in the TExT-MED group compared with a net decrease of -0.1 in the controls ( Δ1.1 [ 95 % CI 0.1 to 2.1 ] ) . Effects were larger among Spanish speakers for both medication adherence ( 1.1 versus -0.3 ; Δ1.4 ; 95 % CI 0.2 to 2.7 ) and Hb A1C ( -1.2 % versus -0.4 % ) in the TExT-MED group . The proportion of patients who used emergency services trended lower in the TExT-MED group ( 35.9 % versus 51.6 % ; Δ15.7 % ; 95 % CI 9.4 % to 22 % ) . Overall , 93.6 % of respondents enjoyed TExT-MED and 100 % would recommend it to family/friends . CONCLUSION The TExT-MED program did not result in a statistically significant improvement in Hb A1C . However , trends toward improvement in the primary outcome of Hb A1C and other secondary outcomes , including quality of life , were observed , the most pronounced being improved medication adherence . TExT-MED also decreased ED utilization . These findings were magnified in the Spanish-speaking subgroup . Technologies such as TExT-MED represent highly scalable , low-cost , and widely accessible solutions for safety-net ED population", "BACKGROUND Control of serum glucose levels is essential for the reduction of complications of diabetes . Telemedicine is one strategy through which serum glucose control can be improved . METHODS A total of 35 adult , insulin-treated patients with diabetes ( type 1 and type 2 ) were enrolled in the present study ( 63.0 + /- 10 years of age , 63 % female ) and r and omized to telemedicine monitoring ( including cordless , remote glucose monitor , and transmitter , n = 17 ) , or conventional follow-up ( n = 18 ) . Metabolic parameters were evaluated , and a quality of life question naire was administered both pre- and post-treatment . RESULTS Groups were similar at baseline in terms of demographic , quality of life , and metabolic parameters . Significant differences in post-treatment metabolic parameters were not observed , although serum glucose was marginally elevated in the control group compared to the telemedicine group ( 214 + /- 65 mg/dL vs. 171 + /- 77 mg/dL , P = 0.09 ) . On the other h and , being clinical ly symptom-free ( 71 % vs. 11 % , P = 0.003 ) , having no hypoglycemic events ( 82 % vs. 17 % , P = 0.0001 ) , and having no hyperglycemic events ( 65 % vs. 17 % , P = 0.004 ) were all significantly more frequently reported in the telemedicine group compared to the control group . Compared to the control group , the telemedicine group reported experiencing significantly less anxiety , treatment difficulty , depression , disease-associated life complications , and feelings of impotence or ineptitude and significantly greater improvement in personal control over glucose , weight , and overall diabetes . CONCLUSIONS Though post-treatment metabolic differences were not observed between treatment groups , the telemedicine group reported significantly greater post-treatment experiences of improved quality of life and sense of control over the disease . Thus patient satisfaction can be enhanced through the use of telemedicine", "BACKGROUND The aim of this study is to evaluate the effect of a web-based comprehensive information system , consisting of Internet and cellular phone use , on blood glucose control . METHODS We established eMOD ( electronic Management of Diabetes ) , a web-based ubiquitous information system , for cell phone users along with a website for Internet users to provide diabetes education . We examined whether this information system has the same impact on glycemic control as conventional education for the diabetes patient . Forty volunteers were enrolled and r and omly assigned to either the eMOD experimental group ( n = 20 ) or the control group ( n = 20 ) . Blood glucose and glycated hemoglobin ( A1C ) levels were evaluated at baseline and after 6 months . RESULTS The two groups were homogeneous in terms of age , sex , and diabetes ' duration at baseline . A1C ( from 9.0 + /- 2.3 % to 7.5 + /- 1.4 % , P = 0.031 ) and postpr and ial glucose level ( 228.1 + /- 79.7 to 173.5 + /- 50.2 mg/dL , P = 0.030 ) were significantly decreased over time in the intervention group but not in the control group . There was a significant relationship between the change in A1C and the frequency of access to the eMOD system via cellular phone ( r = 0.766 , P = 0.03 ; coefficient -0.147 ) . CONCLUSIONS A1C was improved by a web-based intervention not only via computer but also via cellular phone at 6 months post-initiation in patients with type 2 diabetes . These results indicate that the use of a convenient web-based education system could be more effective for glycemic control than traditional education for diabetes patients", "We conducted a r and omized controlled trial using mobile health technology in an ethnically diverse sample of 137 patients with complicated diabetes . Patients in the intervention group ( n = 72 ) were trained to measure their blood glucose with a sensor which transmitted the readings to a mobile phone via a Bluetooth wireless link . Clinicians were then able to examine and respond to the readings which were viewed with a web-based application . Patients in the control arm of the study ( n = 65 ) did not transmit their readings and received care with their usual doctor in the outpatient and /or primary care setting . The mean follow-up period was 9 months in each group . The default rate was higher in the patients in the intervention arm due to technical problems . In an intention-to-treat analysis there were no differences in HbA1c between the intervention and control groups . In a sub-group analysis of the patients who completed the study , the telemonitoring group had a lower HbA1c than those in the control group : 7.76 % and 8.40 % , respectively ( P = 0.06 )" ]